UnificationXref1776
type: UnificationXref
id: 5611778
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611778

SequenceSite692
type: SequenceSite
position status: EQUAL
sequence position: 379

UnificationXref1775
type: UnificationXref
id: 5611777
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611777

SequenceSite691
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref1778
type: UnificationXref
id: 5611780
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611780

SequenceSite690
type: SequenceSite
position status: EQUAL
sequence position: 204

Evidence749
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19923268
xref: http://identifiers.org/pubmed/20462400
xref: http://identifiers.org/pubmed/21102611
xref: http://identifiers.org/pubmed/23514139
xref: http://identifiers.org/pubmed/17768054
xref: http://identifiers.org/pubmed/20674646
comment: Small Ubiquitin-like MOdifiers (SUMOs) are a family of 3 proteins (SUMO1,2,3) that are reversibly conjugated to lysine residues of target proteins via a glycine-lysine isopeptide bond (reviewed in Hay 2013, Hannoun et al. 2010, Gareau and Lima 2010, Wilkinson and Henley 2010, Wang and Dasso 2009). Proteomic methods have yielded estimates of hundreds of target proteins. Targets are mostly located in the nucleus and therefore SUMOylation disproportionately affects gene expression. SUMOs are initially translated as proproteins possessing extra amino acid residues at the C-terminus which are removed by the SUMO processing endoproteases SENP1,2,5 (Hay 2007). Different SENPs have significantly different efficiencies with different SUMOs. The processing exposes a glycine residue at the C-terminus that is activated by ATP-dependent thiolation at cysteine-173 of UBA2 in a complex with SAE1, the E1 complex. The SUMO is transferred from E1 to cysteine-93 of a single E2 enzyme, UBC9 (UBE2I). UBC9 with or, in some cases, without an E3 ligase conjugates the glycine C-terminus of SUMO to an epsilon amino group of a lysine residue on the target protein. SUMO2 and SUMO3 may then be further polymerized, forming chains. SUMO1 is unable to form polymers. Conjugated SUMO can act as a biinding site for proteins possessing SUMO interaction motifs (SIMs) and can also directly affect the formation of complexes between the target protein and other proteins. Conjugated SUMOs are removed by cleavage of the isopeptide bond by processing enzymes SENP1,2,3,5. The processing enzymes SENP6 and SENP7 edit chains of SUMO2 and SUMO3.

UnificationXref1777
type: UnificationXref
id: 5611779
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611779

Evidence748
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16738315
xref: http://identifiers.org/pubmed/19923268
xref: http://identifiers.org/pubmed/20462400
xref: http://identifiers.org/pubmed/21102611
xref: http://identifiers.org/pubmed/16738331
xref: http://identifiers.org/pubmed/17768054
xref: http://identifiers.org/pubmed/12192048
xref: http://identifiers.org/pubmed/17591783
xref: http://identifiers.org/pubmed/20674646
xref: http://identifiers.org/pubmed/16253240
xref: http://identifiers.org/pubmed/17099700
xref: http://identifiers.org/pubmed/11896061
xref: http://identifiers.org/pubmed/14563852
xref: http://identifiers.org/pubmed/17099698
comment: The initial translation products of SUMO1, SUMO2, and SUMO3 are precursors that have extra amino acid residues at the C-terminus (reviewed in Wang and Dasso 2009, Wilkinson and Henley 2010, Hannoun et al. 2010, Gareau and Lima 2010, Hay 2007). SUMO1 has 4 extra residues, SUMO2 has 2 extra residues, and SUMO3 has 11 extra residues. Proteolytic cleavage by SUMO peptidases (SENPs) removes the propeptide and leaves diglycine residues at the C-terminus. Each SENP has distinct preferences for certain SUMOs. SENP1 has highest activity on SUMO1; SENP2 and SENP5 have highest activity on SUMO2 (Shen et al. 2006, Reverter and Lima 2006, Mikolajczyk et al. 2007). SENP1 and SENP2 are predominantly nucleoplasmic (Bailey and O'Hare 2004, Kim et al. 2005, Zhang et al. 2002, Hang and Dasso 2002, Itahana et al. 2006) and SENP5 is predominantly nucleolar (Di Bacco et al. 2006, Gong and Yeh 2006), therefore the processing reactions are believed to occur in the nucleus. The processed SUMO is then activated by formation of a thioester bond with a cysteine residue of an E1 enzyme, UBA2 (SAE2) in a complex with SAE1. SUMO is then transferred from the E1 enzyme to an E2 enzyme, UBC9 (UBE2I).

SequenceSite696
type: SequenceSite
position status: EQUAL
sequence position: 379

UnificationXref1779
type: UnificationXref
id: 5611781
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611781

SequenceSite695
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite694
type: SequenceSite
position status: EQUAL
sequence position: 204

SequenceSite693
type: SequenceSite
position status: EQUAL
sequence position: 202

SequenceSite699
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite698
type: SequenceSite
position status: EQUAL
sequence position: 379

SequenceSite697
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref799
type: UnificationXref
id: 5609246
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609246

UnificationXref798
type: UnificationXref
id: P07280
db: UniProt

UnificationXref797
type: UnificationXref
id: 5609242
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609242

S-methyl-5-thio-?-D-ribose 1-phosphate(2?)
type: SmallMoleculeReference
name: ChEBI:58533 S-methyl-5-thio-?-D-ribose 1-phosphate(2?)
xref: UnificationXref10063

UnificationXref796
type: UnificationXref
id: P07281
db: UniProt

UnificationXref795
type: UnificationXref
id: 5609300
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609300

Evidence742
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11451954
xref: http://identifiers.org/pubmed/19107418
comment: The UBA2:SAE1 complex catalyzes the formation of a thioester bond between SUMO3 and cysteine-173 of UBA2 (Tatham et al. 2001, Werner et al. 2009). ATP reacts with the C-terminal glycine residue of SUMO3 to yield pyrophosphate and a transient intermediate, SUMO3 adenylate, which then reacts with the thiol group of the cysteine residue on UBA2.

UnificationXref794
type: UnificationXref
id: 5609299
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609299

Evidence743
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19923268
xref: http://identifiers.org/pubmed/21102611
xref: http://identifiers.org/pubmed/20164921
xref: http://identifiers.org/pubmed/20674646
comment: The UBA2:SAE1 complex catalyzes the formation of a thioester linkage between the C-terminal glycine of the mature SUMO and a cysteine residue (cysteine-173) in UBA2 (SAE2) (reviewed in Wang and Dasso 2009, Wilkinson and Henley 2010, Hannoun et al. 2010, Gareau and Lima 2010). During the process the C-terminal glycine residue of SUMO is reacted with ATP to yield pyrophosphate and a transient intermediate, SUMO adenylate. The SUMO adenylate then reacts with the thiol group of the cysteine residue of UBA2 (Olsen et al. 2010).

UnificationXref793
type: UnificationXref
id: P0C0T4
db: UniProt

Evidence740
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/20164921
xref: http://identifiers.org/pubmed/10187858
xref: http://identifiers.org/pubmed/20501649
xref: http://identifiers.org/pubmed/19107418
xref: http://identifiers.org/pubmed/9920803
comment: The UBA2:SAE1 complex catalyzes the formation of a thioester bond between SUMO1 and cysteine-173 of UBA2 (Desterro et al. 1999, Okuma et al. 1999, Werner et al. 2009, Olsen et al. 2010, Wang and Chen 2010). ATP reacts with the C-terminal glycine residue of SUMO1 to yield pyrophosphate and a transient intermediate, SUMO1 adenylate, which then reacts with the thiol group of the cysteine residue on UBA2.

UnificationXref1770
type: UnificationXref
id: 5611764
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611764

UnificationXref792
type: UnificationXref
id: 5609295
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609295

Evidence741
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11451954
xref: http://identifiers.org/pubmed/19107418
comment: The UBA2:SAE1 complex catalyzes the formation of a thioester bond between SUMO2 and cysteine-173 of UBA2 (Tatham et al. 2001, Werner et al. 2009). ATP reacts with the C-terminal glycine residue of SUMO2 to yield pyrophosphate and a transient intermediate, SUMO2 adenylate, which then reacts with the thiol group of the cysteine residue on UBA2.

UnificationXref1771
type: UnificationXref
id: 5611769
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611769

UnificationXref791
type: UnificationXref
id: Q3E792
db: UniProt

Evidence746
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11451954
xref: http://identifiers.org/pubmed/19107418
comment: SUMO3 is transferred from cysteine-173 of UBA2 to cysteine-93 of UBC9 (UBE2I) in a transthiolation reaction (Tatham et al. 2001, Werner et al. 2009).

UnificationXref1772
type: UnificationXref
id: 5611774
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611774

UnificationXref790
type: UnificationXref
id: 5609282
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609282

Evidence747
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19923268
xref: http://identifiers.org/pubmed/20462400
xref: http://identifiers.org/pubmed/21102611
xref: http://identifiers.org/pubmed/20674646
comment: SUMO is transferred from cysteine-173 of UBA2 to cysteine-93 of UBC9 (UBE2I) in a transthiolation reaction (reviewed in Wang and Dasso 2009, Wilkinson and Henley 2010, Hannoun et al. 2010, Gareau and Lima 2010). UBC9 is the only known E2 enzyme for SUMO and on certain substrates such as RanGAP1 may act without the requirement of an E3 ligase.

UnificationXref1773
type: UnificationXref
id: 5611775
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611775

Evidence744
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19443651
xref: http://identifiers.org/pubmed/12641448
xref: http://identifiers.org/pubmed/17643372
xref: http://identifiers.org/pubmed/10187858
xref: http://identifiers.org/pubmed/19107418
xref: http://identifiers.org/pubmed/15660128
xref: http://identifiers.org/pubmed/9920803
comment: SUMO1 is transferred from cysteine-173 of UBA2 to cysteine-93 of UBC9 (UBE2I) in a transthiolation reaction (Desterro et al. 1999, Okuma et al. 1999, Tatham et al. 2003, Lois and Lima 2005, Wang et al. 2007, Werner et al. 2009). The UbL domain of E1 recruits E2 into proximity for the transfer of SUMO (Lois and Lima 2005, Wang et al. 2009),

UnificationXref1774
type: UnificationXref
id: 5611776
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611776

Evidence745
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11451954
xref: http://identifiers.org/pubmed/19107418
comment: SUMO2 is transferred from cysteine-173 of UBA2 to cysteine-93 of UBC9 (UBE2I) in a transthiolation reaction (Tatham et al. 2001, Werner et al. 2009).

UnificationXref1767
type: UnificationXref
id: 5611749
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611749

UnificationXref1766
type: UnificationXref
id: 5611744
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611744

Evidence759
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9631292
xref: http://identifiers.org/pubmed/16549443
xref: http://identifiers.org/pubmed/11815450
xref: http://identifiers.org/pubmed/16714477
xref: http://identifiers.org/pubmed/11815463
comment: The generation of insulin-containing secretory granules from proinsulin in the lumen of the endoplasmic reticulum (ER) can be described in 4 steps: formation of intramolecular disulfide bonds, formation of proinsulin-zinc-calcium complexes, proteolytic cleavage of proinsulin to yield insulin, translocation of the granules across the cytosol to the plasma membrane. Transcription of the human insulin gene INS is activated by 4 important transcription factors: Pdx-1, MafA, Beta2/NeuroD1, and E47. The transcription factors interact with each other at the promoters of the insulin gene and act synergistically to promote transcription. Expression of the transcription factors is upregulated in response to glucose. The preproinsulin mRNA is translated by ribosomes at the rough endoplasmic reticulum (ER) and the preproinsulin enters the secretion pathway by virtue of its signal peptide, which is cleaved during translation to yield proinsulin. Evidence indicates that the preproinsulin mRNA is stabilized by glucose. In the process annotated in detail here, within the ER, three intramolecular disulfide bonds form between cysteine residues in the proinsulin. Formation of the bonds is the spontaneous result of the conformation of proinsulin and the oxidizing environment of the ER, which is maintained by Ero1-like alpha The cystine bonded proinsulin then moves via vesicles from the ER to the Golgi Complex. High concentrations of zinc are maintained in the Golgi by zinc transporters ZnT5, ZnT6, and ZnT7 and the proinsulin forms complexes with zinc and calcium. Proinsulin-zinc-calcium complexes bud in vesicles from the trans-Golgi to form immature secretory vesicles (secretory granules) in the cytosol. Within the immature granules the endoproteases Prohormone Convertase 1/3 and Prohormone Convertase 2 cleave at two sites of the proinsulin and Carboxypeptidase E removes a further 4 amino acid residues to yield the cystine-bonded A and B chains of mature insulin and the C peptide, whic…

UnificationXref1765
type: UnificationXref
id: 5611743
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611743

SequenceSite681
type: SequenceSite
position status: EQUAL
sequence position: 393

UnificationXref1764
type: UnificationXref
id: 5611741
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611741

SequenceSite680
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite683
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite682
type: SequenceSite
position status: EQUAL
sequence position: 161

UnificationXref1769
type: UnificationXref
id: 5611759
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611759

SequenceSite685
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref1768
type: UnificationXref
id: 5611754
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611754

SequenceSite684
type: SequenceSite
position status: EQUAL
sequence position: 297

SequenceSite687
type: SequenceSite
position status: EQUAL
sequence position: 2

http://identifiers.org/pubmed/9809442
type: PublicationXref
id: 9809442
author: Marin-Garcia, J
author: Ananthakrishnan, R
author: Goldenthal, MJ
db: Pubmed
title: Cloning and molecular analysis of the human citrate synthase gene
source: Genome 41:733-738
year: 1998

http://identifiers.org/pubmed/11903050
type: PublicationXref
id: 11903050
author: MacMullen, CM
author: Smith, TJ
author: Poncz, M
author: Hsu, BY
author: Fang, J
author: Stanley, CA
db: Pubmed
title: Expression, purification and characterization of human glutamate dehydrogenase (GDH) allosteric regulatory mutations
source: Biochem J 363:81-7
year: 2002

SequenceSite686
type: SequenceSite
position status: EQUAL
sequence position: 379

SequenceSite689
type: SequenceSite
position status: EQUAL
sequence position: 202

SequenceSite688
type: SequenceSite
position status: EQUAL
sequence position: 379

UnificationXref789
type: UnificationXref
id: 5609281
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609281

UnificationXref786
type: UnificationXref
id: P0CX30
db: UniProt

UnificationXref785
type: UnificationXref
id: 5609207
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609207

UnificationXref788
type: UnificationXref
id: P0CX29
db: UniProt

UnificationXref787
type: UnificationXref
id: 5609279
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609279

Evidence750
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: After translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the body. These modifications include the internal peptide bond cleavages that activate proenzymes, the attachment of oligosaccharide moieties to membrane-bound and secreted proteins, the attachment of lipid or glycolipid moieties that serve to anchor proteins to cellular membranes, and the vitamin K-dependent attachment of carboxyl groups to glutamate residues.

http://identifiers.org/pubmed/10676816
type: PublicationXref
id: 10676816
author: Cerione, RA
author: Nassar, N
author: Hoffman, GR
db: Pubmed
title: Structure of the Rho family GTP-binding protein Cdc42 in complex with the multifunctional regulator RhoGDI
source: Cell 100:345-56
year: 2000

RHO4
type: ProteinReference
name: UniProt:Q00246
xref: UnificationXref3028
organism: http://identifiers.org/taxonomy/4932

http://identifiers.org/pubmed/8774846
type: PublicationXref
id: 8774846
author: Cohen, P
author: Young, P R
author: Clifton, A D
db: Pubmed
title: A comparison of the substrate specificity of MAPKAP kinase-2 and MAPKAP kinase-3 and their activation by cytokines and cellular stress
source: FEBS Lett. 392:209-14
year: 1996

UnificationXref782
type: UnificationXref
id: 5609202
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609202

Evidence751
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19453276
xref: http://identifiers.org/pubmed/18174896
comment: As inferred from the yeast TIM23 complex, the human TIMM23 complex resides in the inner membrane of the mitochondrion and transfers precursor proteins to the inner membrane. The TIMM23 complex appears to adopt different configurations (and perhaps different subunit compositions) depending on whether the substrate is destined for the inner membrane or the matrix. Here we refer to the TIMM23 SORT complex as the configuration that delivers inner membrane proteins. The TIMM21 subunit is required for this activity. In yeast, the N-terminal presequences of precursors first interact with TIM50 and TIM23 (TIMM50 and TIMM23 in human). The TIM17 and TIM23 subunits (TIMM17 and TIMM23 in human) form a channel and are required to initiate translocation of precursors. In yeast experimentally verified substrates of the TIM23 SORT complex targeted to the inner membrane include CYB2, DLD (LDHD in human), ATP9 (ATP5G1 in human), COQ2, TIM54 (TIMM54 in human), COX4, COX5A, and ATP2 (ATP5B in human). Many other inner membrane proteins are believed to be substrates of the TIMM23 complex.

UnificationXref781
type: UnificationXref
id: P06367
db: UniProt

Evidence752
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19453276
xref: http://identifiers.org/pubmed/18174896
comment: As inferred from yeast, the alpha subunit of the mitochondrial processing peptidase (MPP) binds presequences of mitochondrial precursors and the beta subunit cleaves the presequence. After cleavage, proteins destined for the inner membrane are released laterally from TIMM23 SORT into the membrane.

UnificationXref784
type: UnificationXref
id: 5609206
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609206

Evidence753
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19453276
xref: http://identifiers.org/pubmed/18174896
comment: As inferred from the yeast TIM23 complex, the human TIMM23 complex resides in the inner membrane of the mitochondrion and transfers precursor proteins to the inner membrane. The presequences of proteins targeted to the inner membrane are transferred to the matrix where they are cleaved. Sequences in the mature regions of the proteins then interact with the TIMM23 complex to halt transfer across the inner membrane and the proteins are released laterally into the inner membrane. TIMM21 is required. In yeast experimentally verified substrates of the TIM23 complex targeted to the inner membrane include CYB2, DLD (LDHD in human), ATP9 (ATP5G1 in human), COQ2, TIM54 (TIMM54 in human), COX4, COX5A, and ATP2 (ATP5B in human). Many other inner membrane proteins are believed to be substrates of the TIMM23 complex.

UnificationXref783
type: UnificationXref
id: P39516
db: UniProt

Evidence754
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19453276
xref: http://identifiers.org/pubmed/18174896
comment: As inferred from the yeast TIM23 complex, the human TIMM23 complex resides in the inner membrane of the mitochondrion and transfers precursor proteins to the matrix. The TIMM23 complex appears to adopt different configurations (and perhaps different subunit compositions) depending on whether the substrate is destined for the inner membrane or the matrix. Here we refer to the TIMM23 PAM complex as the configuration that delivers inner membrane proteins. The PAM17 subcomplex is required for this activity. The N-terminal presequence of precursors first interacts with TIMM50 and TIMM23. The TIMM17 and TIMM23 subunits form a channel and are required to initiate translocation of precursors. In yeast experimentally verified substrates of TIM23:PAM include Hsp60 (HSP60 in human) and Yfh1 (Frataxin, FXN in human). Many other matrix proteins are believed to be substrates of the TIMM23 complex.

UnificationXref1762
type: UnificationXref
id: 5611807
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611807

Evidence755
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19453276
xref: http://identifiers.org/pubmed/18174896
comment: As inferred from yeast, the alpha subunit of the mitochondrial processing peptidase (MPP) binds presequences of mitochondrial precursors and the beta subunit cleaves the presequence. After cleavage, proteins destined for the matrix are drawn into the matrix by ATP-dependent interaction with mtHSP70 (HSPA9, homolog of yeast SSC1) of the PAM complex.

UnificationXref1763
type: UnificationXref
id: REACT_191665
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_191665.3

Evidence756
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18678864
xref: http://identifiers.org/pubmed/19453276
xref: http://identifiers.org/pubmed/18174896
comment: As inferred from the yeast TIM23 complex, the human TIMM23 complex transports precursor proteins across the inner membrane and into the matrix. As in yeast, subunits TIMM50, TIMM17, and TIMM23 are probably necessary for initiating translocation while the PAM complex with mtHSP70 (HSPA9, yeast SSC1) provides the motive force that drives the transport. mtHSP70 binding to the precursor pulls the protein into the matrix in a reaction requiring ATP hydrolysis. The yeast reaction appears to use a Brownian ratchet mechanism (Yamano et al. 2008). In yeast experimentally verified substrates of TIM23 PAM include Hsp60 (HSP60 in human) and Yfh1 (Frataxin, FXN in human). Many other matrix proteins are believed to be substrates of the TIMM23 complex

UnificationXref1760
type: UnificationXref
id: 5611828
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611828

UnificationXref780
type: UnificationXref
id: 5609341
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609341

Evidence757
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17696772
xref: http://identifiers.org/pubmed/19767391
xref: http://identifiers.org/pubmed/19720617
xref: http://identifiers.org/pubmed/17998403
xref: http://identifiers.org/pubmed/20100523
xref: http://identifiers.org/pubmed/20214493
xref: http://identifiers.org/pubmed/17996737
xref: http://identifiers.org/pubmed/19453276
xref: http://identifiers.org/pubmed/18174896
comment: A human mitochondrion contains about 1500 proteins, more than 99% of which are encoded in the nucleus, synthesized in the cytosol and imported into the mitochondrion. Proteins are targeted to four locations (outer membrane, intermembrane space, inner membrane, and matrix) and must be sorted accordingly (reviewed in Kutik et al. 2007, Milenkovic et al. 2007, Bolender et al. 2008, Endo and Yamano 2009). Newly synthesized proteins are transported from the cytosol across the outer membrane by the TOMM40:TOMM70 complex. Proteins that contain presequences first interact with the TOMM20 subunit of the complex while proteins that contain internal targeting elements first interact with the TOMM70 subunit. After initial interaction the protein is conducted across the outer membrane by TOMM40 subunits. In yeast some proteins such as Aco1, Atp1, Cit1, Idh1, and Atp2 have both presequences that interact with TOM20 and mature regions that interact with TOM70 (Yamamoto et al. 2009). After passage across the outer membrane, proteins may be targeted to the outer membrane via the SAMM50 complex, to the inner membrane via the TIMM22 or TIMM23 complexes (reviewed in van der Laan et al. 2010), to the matrix via the TIMM23 complex (reviewed in van der Laan et al. 2010), or proteins may fold and remain in the intermembrane space (reviewed in Stojanovski et al. 2008, Deponte and Hell 2009, Sideris and Tokatlidis 2010). Presequences on matrix and inner membrane proteins cause interaction with TIMM23 complexes; internal targeting sequences cause outer membrane proteins to interact with the SAMM50 complex and inner membrane proteins to interact with the TIMM22 complex. While in the intermembrane space hydrophobic proteins are chaperoned by the TIMM8:TIMM13 complex and/or the TIMM9:TIMM10:FXC1 complex.

UnificationXref1761
type: UnificationXref
id: REACT_212396
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_212396.2

Evidence758
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11904301
comment: The human gene SLC30A5 encodes the zinc transporter ZnT5. This protein is widely expressed but is most abundant in pancreatic beta cells (Kambe T et al, 2002). In these cells, ZnT5 mediates the transport of zinc into secretory granules that contain insulin.

UnificationXref1758
type: UnificationXref
id: REACT_260825
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_260825.1

SequenceSite674
type: SequenceSite
position status: EQUAL
sequence position: 2

Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction693
pathway component: BiochemicalReaction688
pathway component: BiochemicalReaction692
pathway component: BiochemicalReaction694
pathway component: BiochemicalReaction690
pathway component: BiochemicalReaction691
pathway component: BiochemicalReaction689
evidence: Evidence1214
xref: RelationshipXref859
xref: UnificationXref7920
xref: UnificationXref7921
pathway order: PathwayStep1197
pathway order: PathwayStep1193
pathway order: PathwayStep1194
pathway order: PathwayStep1195
pathway order: PathwayStep1196
pathway order: PathwayStep1191
pathway order: PathwayStep1192
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref1757
type: UnificationXref
id: 5617999
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617999

SequenceSite673
type: SequenceSite
position status: EQUAL
sequence position: 222

SequenceSite672
type: SequenceSite
position status: EQUAL
sequence position: 218

UnificationXref3899
type: UnificationXref
id: 379727
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379727

UnificationXref1759
type: UnificationXref
id: 5611827
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611827

SequenceSite671
type: SequenceSite
position status: EQUAL
sequence position: 393

UnificationXref3898
type: UnificationXref
id: CHEBI:29171
db: ChEBI

UnificationXref1754
type: UnificationXref
id: REACT_240179
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_240179.1

SequenceSite670
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref1753
type: UnificationXref
id: 5618002
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618002

UnificationXref1756
type: UnificationXref
id: REACT_224255
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_224255.2

UnificationXref1755
type: UnificationXref
id: 5618339
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618339

SequenceSite679
type: SequenceSite
position status: EQUAL
sequence position: 393

SequenceSite678
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite677
type: SequenceSite
position status: EQUAL
sequence position: 292

SequenceSite676
type: SequenceSite
position status: EQUAL
sequence position: 286

SequenceSite675
type: SequenceSite
position status: EQUAL
sequence position: 393

Evidence760
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/21805235
xref: http://identifiers.org/pubmed/2663045
comment: Peptide hormones are cleaved from larger precursors in the secretory system (endoplasmic reticulum, Golgi apparatus, secretory granules) of the cell. After secretion peptide hormones are modified and degraded by extracellular proteases.

Evidence761
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/14973138
comment: The BIP (HSPA5) gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

http://identifiers.org/pubmed/18442489
type: PublicationXref
id: 18442489
author: Wallace, JC
author: Pendini, Nicole R
author: Wilce, Matthew C
author: Polyak, Steven W
author: Booker, Grant W
author: Bailey, Lisa M
db: Pubmed
title: Microbial biotin protein ligases aid in understanding holocarboxylase synthetase deficiency
source: Biochim. Biophys. Acta 1784:973-82
year: 2008

http://identifiers.org/pubmed/18414735
type: PublicationXref
id: 18414735
author: Kufer, TA
db: Pubmed
title: Signal transduction pathways used by NLR-type innate immune receptors
source: Mol Biosyst 4:380-6
year: 2008

Mitochondrial protein import
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction402
pathway component: BiochemicalReaction401
pathway component: BiochemicalReaction406
pathway component: BiochemicalReaction405
pathway component: BiochemicalReaction404
pathway component: BiochemicalReaction403
evidence: Evidence757
xref: RelationshipXref439
xref: UnificationXref5216
xref: UnificationXref5215
pathway order: PathwayStep740
pathway order: PathwayStep742
pathway order: PathwayStep741
pathway order: PathwayStep744
pathway order: PathwayStep743
pathway order: PathwayStep739
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref3892
type: UnificationXref
id: REACT_7747
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_7747.2

Evidence768
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16539657
comment: The CTDSP2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

UnificationXref1750
type: UnificationXref
id: REACT_252897
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_252897.1

UnificationXref3893
type: UnificationXref
id: 5613596
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613596

Evidence769
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16539657
comment: The DCTN1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

UnificationXref1751
type: UnificationXref
id: 5618001
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618001

UnificationXref3890
type: UnificationXref
id: REACT_15557
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15557.1

Evidence766
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Phosphorylation of the C-terminal region causes a loop in the C-terminus to change position, enabling access to an ADP-binding pocket. Phosphorylated IRE1-alpha dimers bind ADP in preference to ATP.

UnificationXref1752
type: UnificationXref
id: REACT_244741
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_244741.1

UnificationXref3891
type: UnificationXref
id: 159450
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159450

Evidence767
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16539657
comment: The ATP6VOD1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

UnificationXref3896
type: UnificationXref
id: 374064
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374064

Evidence764
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16365312
xref: http://identifiers.org/pubmed/10835430
xref: http://identifiers.org/pubmed/11069889
xref: http://identifiers.org/pubmed/18191223
xref: http://identifiers.org/pubmed/11897784
xref: http://identifiers.org/pubmed/16973740
comment: The dissociation of the IRE1-alpha:BiP heterodimer liberates IRE1-alpha, which forms homodimers. Dimer formation is initiated by interaction between the N-terminal, luminal domains.

UnificationXref3897
type: UnificationXref
id: REACT_15639
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15639.2

Evidence765
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11069889
xref: http://identifiers.org/pubmed/16973740
xref: http://identifiers.org/pubmed/9637683
comment: Dimerization of the N-terminal luminal regions of IRE1-alpha brings the cytosolic C-terminal regions in proximity. The C-terminal region possesses kinase activity and the homodimer trans-autophosphorylates. From homology with Saccharomyces IRE1-alpha the phosphorylation of human IRE1-alpha is believed to be at Ser724.

UnificationXref3894
type: UnificationXref
id: 5613598
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613598

Evidence762
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/14973138
xref: http://identifiers.org/pubmed/10866666
xref: http://identifiers.org/pubmed/10958673
xref: http://identifiers.org/pubmed/10856300
comment: The N-terminal fragment of ATF6-alpha contains a bZIP domain and binds the sequence CCACG in ER Stress Response Elements (ERSEs). ATF6-alpha binds ERSEs together with the heterotrimeric transcription factor NF-Y, which binds the sequence CCAAT in the ERSEs, and together the two factors activate transcription of ER stress-responsive genes. Evidence from overexpression and knockdowns indicates that ATF6-alpha is a potent activator but its homolog ATF6-beta is not and ATF6-beta may actually reduce expression of ER stress proteins.

UnificationXref3895
type: UnificationXref
id: REACT_226949
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_226949.2

Evidence763
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18436705
xref: http://identifiers.org/pubmed/18038217
xref: http://identifiers.org/pubmed/18048764
comment: ATF6-alpha is a transmembrane protein that normally resides in the Endoplasmic Reticulum (ER) membrane. Here its luminal C-terminal domain is associated with BiP, shielding 2 Golgi-targeting regions and thus keeping ATF6-alpha in the ER. Upon interaction of BiP with unfolded proteins in the ER, ATF6-alpha dissociates and transits to the Golgi where it is cleaved by the S1P and S2P proteases that reside in the Golgi, releasing the N-terminal domain of ATF6-alpha into the cytosol. After transiting to the nucleus, the N-terminal domain acts as a transcription factor to activate genes encoding chaperones.

http://identifiers.org/pubmed/642006
type: PublicationXref
id: 642006
author: Gall, JG
author: Blackburn, EH
db: Pubmed
title: A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena
source: J Mol Biol 120:33-53
year: 1978

UnificationXref1749
type: UnificationXref
id: 5618260
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618260

SequenceSite661
type: SequenceSite
position status: EQUAL
sequence position: 347

UnificationXref3888
type: UnificationXref
id: REACT_15767
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15767.1

UnificationXref1748
type: UnificationXref
id: REACT_211772
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_211772.2

SequenceSite660
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref3887
type: UnificationXref
id: 379729
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379729

UnificationXref1747
type: UnificationXref
id: 5618261
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618261

SequenceSite663
type: SequenceSite
position status: EQUAL
sequence position: 211

http://identifiers.org/pubmed/22449188
type: PublicationXref
id: 22449188
author: Schibler, Andria C
author: Koutelou, E
author: Butler, Jill S
author: Dent, Sharon Y R
db: Pubmed
title: Histone-modifying enzymes: regulators of developmental decisions and drivers of human disease
source: Epigenomics 4:163-77
year: 2012

UnificationXref1746
type: UnificationXref
id: REACT_212365
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_212365.2

SequenceSite662
type: SequenceSite
position status: EQUAL
sequence position: 207

UnificationXref3889
type: UnificationXref
id: 379730
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379730

UnificationXref1745
type: UnificationXref
id: 5611248
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611248

UnificationXref1744
type: UnificationXref
id: 5611247
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611247

UnificationXref1743
type: UnificationXref
id: REACT_243575
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_243575.1

UnificationXref1742
type: UnificationXref
id: 5618259
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618259

SequenceSite669
type: SequenceSite
position status: EQUAL
sequence position: 334

SequenceSite668
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite665
type: SequenceSite
position status: EQUAL
sequence position: 334

SequenceSite664
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite667
type: SequenceSite
position status: EQUAL
sequence position: 347

SequenceSite666
type: SequenceSite
position status: EQUAL
sequence position: 1

Evidence770
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16539657
comment: The DDX11 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

Evidence771
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10827079
comment: The DNAJB11 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

Evidence772
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16461360
comment: The EDEM gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

UnificationXref1740
type: UnificationXref
id: 5611220
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611220

Evidence777
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16539657
comment: The GSK3A gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

UnificationXref1741
type: UnificationXref
id: REACT_241716
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_241716.1

UnificationXref3880
type: UnificationXref
id: REACT_2525
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2525.2

Evidence778
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16539657
comment: The HYOU1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

http://identifiers.org/pubmed/17322878
type: PublicationXref
id: 17322878
author: Citri, A
author: Yarden, Y
author: Amit, I
author: Jacob-Hirsch, J
author: Siwak, D
author: Segal, E
author: Lu, Y
author: Tarcic, G
author: Amariglio, N
author: Mills, GB
author: Katz, M
author: Shay, T
author: Vaisman, N
author: Lahad, J
author: Domany, E
author: Rechavi, G
author: Alon, U
author: Zhang, F
db: Pubmed
title: A module of negative feedback regulators defines growth factor signaling
source: Nat Genet 39:503-12
year: 2007

UnificationXref3881
type: UnificationXref
id: 5618066
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618066

Evidence779
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16539657
comment: The KDELR3 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

UnificationXref3882
type: UnificationXref
id: REACT_256513
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_256513.1

UnificationXref3883
type: UnificationXref
id: 113593
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113593

Evidence773
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16539657
comment: The FKBP14 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

UnificationXref3884
type: UnificationXref
id: REACT_3422
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3422.1

Evidence774
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16539657
comment: The GAP gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

UnificationXref3885
type: UnificationXref
id: 379697
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379697

Evidence775
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16539657
comment: The GFPT1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

UnificationXref3886
type: UnificationXref
id: REACT_16024
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_16024.2

Evidence776
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16539657
comment: The GOSR2 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

UnificationXref1739
type: UnificationXref
id: 5611219
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611219

SequenceSite655
type: SequenceSite
position status: EQUAL
sequence position: 424

SequenceSite656
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite653
type: SequenceSite
position status: EQUAL
sequence position: 427

SequenceSite654
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite659
type: SequenceSite
position status: EQUAL
sequence position: 193

SequenceSite657
type: SequenceSite
position status: EQUAL
sequence position: 464

SequenceSite658
type: SequenceSite
position status: EQUAL
sequence position: 189

UnificationXref1731
type: UnificationXref
id: 5615033
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615033

UnificationXref1732
type: UnificationXref
id: 5615034
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615034

UnificationXref1733
type: UnificationXref
id: 5615035
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615035

UnificationXref1734
type: UnificationXref
id: REACT_175373
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_175373.3

UnificationXref1735
type: UnificationXref
id: 5618545
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618545

SequenceSite651
type: SequenceSite
position status: EQUAL
sequence position: 399

UnificationXref3878
type: UnificationXref
id: 5609065
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609065

UnificationXref1736
type: UnificationXref
id: REACT_189247
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_189247.3

SequenceSite652
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref3879
type: UnificationXref
id: 29926
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29926

UnificationXref1737
type: UnificationXref
id: 113499
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113499

UnificationXref3876
type: UnificationXref
id: 5609064
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609064

UnificationXref1738
type: UnificationXref
id: REACT_3748
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3748.1

SequenceSite650
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref3877
type: UnificationXref
id: REACT_241855
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_241855.1

UnificationXref750
type: UnificationXref
id: 5609398
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609398

UnificationXref3875
type: UnificationXref
id: 5609062
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609062

Evidence787
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16461360
xref: http://identifiers.org/pubmed/17612490
xref: http://identifiers.org/pubmed/14559994
xref: http://identifiers.org/pubmed/18664523
xref: http://identifiers.org/pubmed/16539657
comment: Xbp-1 (S) binds the sequence CCACG in ER Stress Responsive Elements (ERSE, consensus sequence CCAAT (N)9 CCACG) located upstream from many genes. The ubiquitous transcription factor NF-Y, a heterotrimer, binds the CCAAT portion of the ERSE and together the IRE1-alpha: NF-Y complex activates transcription of a set of chaperone genes including DNAJB9, EDEM, RAMP4, p58IPK, and others. This results in an increase in protein folding activity in the ER.

UnificationXref751
type: UnificationXref
id: 5609399
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609399

UnificationXref3874
type: UnificationXref
id: 5609061
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609061

Evidence786
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16539657
comment: The YIF1A gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

UnificationXref3873
type: UnificationXref
id: 5609060
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609060

Evidence785
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16539657
comment: The WIPI1 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

UnificationXref3872
type: UnificationXref
id: P28239
db: UniProt

Evidence784
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16539657
comment: The Sec31A gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

UnificationXref3871
type: UnificationXref
id: 5609056
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609056

UnificationXref3870
type: UnificationXref
id: P00817
db: UniProt

UnificationXref1730
type: UnificationXref
id: P06785
db: UniProt

Evidence789
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18840095
comment: The Aspariagine Synthetase (ASNS) gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

Evidence788
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18436705
xref: http://identifiers.org/pubmed/18038217
xref: http://identifiers.org/pubmed/18048764
comment: IRE1-alpha is a single-pass transmembrane protein that resides in the endoplasmic reticulum (ER) membrane. The C-terminus of IRE1-alpha is located in the cytosol; the N-terminus is located in the ER lumen. In unstressed cells IRE1-alpha exists in an inactive heterodimeric complex with BiP such that BiP in the ER lumen binds the N-terminal region of IRE1-alpha. Upon accumulation of unfolded proteins in the ER, BiP binds the unfolded protein and the IRE1-alpha:BiP complex dissociates. The dissociated IRE1-alpha then forms homodimers. Initially the luminal N-terminal regions pair. This is followed by trans-autophosphorylation of IRE1-alpha at Ser724 in the cytosolic C-terminal region. The phosphorylation causes a conformational change that allows the dimer to bind ADP, causing a further conformational change to yield back-to-back pairing of the cytosolic C-terminal regions of IRE1-alpha. The fully paired IRE1-alpha homodimer has endoribonuclease activity and cleaves the mRNA encoding Xbp-1. A 26 residue polyribonucleotide is released and the 5' and 3' fragments of the original Xbp-1 mRNA are rejoined. The spliced Xbp-1 message encodes Xbp-1 (S), a potent activator of transcription. Xbp-1 (S) together with the ubiquitous transcription factor NF-Y bind the ER Stress Responsive Element (ERSE) in a number of genes encoding chaperones. Recent data suggest that the IRE1-alpha homodimer can also cleave specific subsets of mRNAs, including the insulin (INS) mRNA in pancreatic beta cells.

UnificationXref758
type: UnificationXref
id: 5609323
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609323

UnificationXref759
type: UnificationXref
id: Q3E7X9
db: UniProt

UnificationXref756
type: UnificationXref
id: 5609309
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609309

UnificationXref757
type: UnificationXref
id: P0C0X0
db: UniProt

http://identifiers.org/pubmed/9438390
type: PublicationXref
id: 9438390
author: Webster, MK
author: Bardwell, WM
author: Meyer, AN
author: Donoghue, DJ
author: Robertson, SC
author: d'Avis, PY
db: Pubmed
title: Constitutive activation of fibroblast growth factor receptor 3 by mutations responsible for the lethal skeletal dysplasia thanatophoric dysplasia type I
source: Cell Growth Differ 9:71-8
year: 1998

UnificationXref754
type: UnificationXref
id: P39938
db: UniProt

Evidence783
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16539657
comment: The SRPRB gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

UnificationXref755
type: UnificationXref
id: 5609308
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609308

Evidence782
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16539657
comment: The SRPR gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

UnificationXref752
type: UnificationXref
id: P39939
db: UniProt

Evidence781
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16539657
comment: The PPP2R5B gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

UnificationXref753
type: UnificationXref
id: 5609304
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609304

Evidence780
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/7590364
xref: http://identifiers.org/pubmed/12204115
xref: http://identifiers.org/pubmed/15466936
comment: The PDIA6 gene is transcribed to yield mRNA and the mRNA is translated to yield protein.

SequenceSite642
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite643
type: SequenceSite
position status: EQUAL
sequence position: 464

UnificationXref1728
type: UnificationXref
id: 5615031
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615031

SequenceSite644
type: SequenceSite
position status: EQUAL
sequence position: 271

UnificationXref1729
type: UnificationXref
id: 5615032
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615032

SequenceSite645
type: SequenceSite
position status: EQUAL
sequence position: 275

SequenceSite646
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref749
type: UnificationXref
id: P0CX39
db: UniProt

SequenceSite647
type: SequenceSite
position status: EQUAL
sequence position: 419

SequenceSite648
type: SequenceSite
position status: EQUAL
sequence position: 257

SequenceSite649
type: SequenceSite
position status: EQUAL
sequence position: 261

UnificationXref1722
type: UnificationXref
id: 5611246
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611246

UnificationXref3869
type: UnificationXref
id: REACT_221397
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_221397.2

UnificationXref1723
type: UnificationXref
id: P07807
db: UniProt

UnificationXref1720
type: UnificationXref
id: 5618338
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618338

UnificationXref1721
type: UnificationXref
id: REACT_218284
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_218284.2

UnificationXref1726
type: UnificationXref
id: 5615030
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615030

UnificationXref3865
type: UnificationXref
id: REACT_15717
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15717.1

UnificationXref1727
type: UnificationXref
id: P09938
db: UniProt

UnificationXref3866
type: UnificationXref
id: P07806
db: UniProt

UnificationXref1724
type: UnificationXref
id: 5615029
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615029

SequenceSite640
type: SequenceSite
position status: EQUAL
sequence position: 221

UnificationXref3867
type: UnificationXref
id: 5613562
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613562

UnificationXref1725
type: UnificationXref
id: P49723
db: UniProt

SequenceSite641
type: SequenceSite
position status: EQUAL
sequence position: 223

UnificationXref3868
type: UnificationXref
id: 5613564
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613564

UnificationXref3862
type: UnificationXref
id: REACT_15833
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15833.1

Evidence796
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12750892
comment: GABA is loaded into the synaptic vesicle by inihibitory amino acid transport, VIAAT or VGAT.

UnificationXref3861
type: UnificationXref
id: 379793
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379793

Evidence795
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18029057
comment: Acetylcholine neurotransmitter release cycle involves syntheis of choline, loading of clathrin scultpted synaptic vesicles, docking and priming of the acetyl choline loaded synaptic vesicles and then release of acetylcholine. This cycle occurs in neurons of central nervous system (CNS), peripheral, autonomic and somatic nervous system. In the CNS, the acetylcholine is released by the presynaptic neurons into the synaptic cleft where the released acetylcholine is accessible to acetylcholine receptors located on the postsynaptic neurons.

UnificationXref3864
type: UnificationXref
id: 379790
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379790

Evidence798
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19300440
comment: Succinate semialdehyde dehydrogenase (SSADH) converts succinate semialdehyde, in a final step of GABA degradation, into succinate. SSADH uses one water molecule and one molecule of NAD+ per molecule of succinyate semialdehyde.

UnificationXref740
type: UnificationXref
id: P26783
db: UniProt

UnificationXref3863
type: UnificationXref
id: CHEBI:29164
db: ChEBI

Evidence797
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/7851425
comment: GABA is converted to succinate semialdehyde by 4-aminobutyrate aminotransferase

Evidence799
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19172412
comment: GABA is metabolized to succinated by the serial action of two enzymes, 4-aminobutyrate aminotransferase and suucinate semialdehyde dehydrogenase.

UnificationXref3860
type: UnificationXref
id: CHEBI:29183
db: ChEBI

http://identifiers.org/pubmed/9188485
type: PublicationXref
id: 9188485
author: Folk, JE
author: Park, MH
author: Wolff, EC
db: Pubmed
title: Enzyme-substrate intermediate formation at lysine 329 of human deoxyhypusine synthase
source: J Biol Chem 272:15865-71
year: 1997

UnificationXref745
type: UnificationXref
id: 5609416
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609416

RPC5
type: ProteinReference
name: YPR110C
name: RPC40
name: UniProt:P07703 RPC40
name: P8283.18
name: RPA5
xref: UnificationXref959
comment: MISCELLANEOUS Present with 13000 molecules/cell in log phase SD medium.SIMILARITY Belongs to the archaeal RpoD/eukaryotic RPB3 RNA polymerase subunit family.
organism: http://identifiers.org/taxonomy/4932

UnificationXref746
type: UnificationXref
id: 5609417
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609417

SequenceSite639
type: SequenceSite
position status: EQUAL
sequence position: 424

UnificationXref747
type: UnificationXref
id: P0CX40
db: UniProt

Evidence790
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16912112
xref: http://identifiers.org/pubmed/20022965
xref: http://identifiers.org/pubmed/18840095
xref: http://identifiers.org/pubmed/16687408
xref: http://identifiers.org/pubmed/18426796
xref: http://identifiers.org/pubmed/16931790
xref: http://identifiers.org/pubmed/14630918
xref: http://identifiers.org/pubmed/14742429
comment: ATF4 is a transcription factor and activates expression of IL-8, MCP1, IGFBP-1, CHOP, HERP1 and ATF3.

UnificationXref748
type: UnificationXref
id: 5609396
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609396

UnificationXref741
type: UnificationXref
id: 5609372
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609372

Evidence792
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18436705
xref: http://identifiers.org/pubmed/15952902
xref: http://identifiers.org/pubmed/18038217
xref: http://identifiers.org/pubmed/18048764
xref: http://identifiers.org/pubmed/16365312
comment: The Unfolded Protein Response (UPR) is a regulatory system that protects the Endoplasmic Reticulum (ER) from overload. The UPR is provoked by the accumulation of improperly folded protein in the ER during times of unusually high secretion activity. Analysis of mutants with altered UPR, however, shows that the UPR is also required for normal development and function of secretory cells. One level at which the URP operates is transcriptional and translational regulation: mobilization of ATF6 and IRE1 leads to increased transcription of genes encoding chaperones, and mobilization of PERK (pancreatic eIF2alpha kinase, EIF2AK3) leads to phosphorylation of the translation initiation factor eIF2alpha and global down-regulation of protein synthesis. These three regulatory pathways are annotated here.

UnificationXref742
type: UnificationXref
id: P32905
db: UniProt

Evidence791
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18436705
xref: http://identifiers.org/pubmed/18038217
xref: http://identifiers.org/pubmed/17956313
xref: http://identifiers.org/pubmed/18048764
comment: PERK (EIF2AK3) is a single-pass transmembrane protein located in the endoplasmic reticulum (ER) membrane such that the N-terminus of PERK is luminal and the C-terminus is cytosolic. PERK is maintained in an inactive form by interaction of its luminal domain with BiP, an ER chaperone. BiP also binds unfolded proteins and so BiP dissociates from PERK when unfolded proteins accumulate in the ER. Dissociated PERK monomers spontaneously form homodimers and the homodimeric form of PERK possesses kinase activity in its cytosolic C-terminal domain. The kinase specifically phosphorylates the translation factor eIF2alpha at Ser52, resulting in an arrest of translation. Thus translation of proteins targeted to the ER is downregulated. The translation arrest also causes depletion of Cyclin D1, a rapidly turned over protein. The depletion of Cyclin D1 in turn causes arrest of the cell cycle in G1 phase.

UnificationXref743
type: UnificationXref
id: 5609412
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609412

Evidence794
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/1339386
comment: In the cytosol, choline O-acetyltransferase (CHAT) acetylates choline (Cho) to produce acetylcholine (AcCho) (Toussaint 1992). AcCho is synthesised in the cytoplasm of cholinergic neurons from acetyl-CoA and Cho by CHAT enzyme.

UnificationXref744
type: UnificationXref
id: P46654
db: UniProt

Evidence793
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Protein metabolism comprises the pathways of translation, post-translational modification and protein folding.

SequenceSite637
type: SequenceSite
position status: EQUAL
sequence position: 185

SequenceSite638
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite635
type: SequenceSite
position status: EQUAL
sequence position: 427

SequenceSite636
type: SequenceSite
position status: EQUAL
sequence position: 183

UnificationXref1717
type: UnificationXref
id: REACT_232488
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_232488.1

SequenceSite633
type: SequenceSite
position status: EQUAL
sequence position: 464

UnificationXref1718
type: UnificationXref
id: 5611999
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611999

SequenceSite634
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref1719
type: UnificationXref
id: REACT_224926
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_224926.2

SequenceSite631
type: SequenceSite
position status: EQUAL
sequence position: 424

SequenceSite632
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref1713
type: UnificationXref
id: REACT_238662
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_238662.1

UnificationXref3856
type: UnificationXref
id: 5613535
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613535

UnificationXref1714
type: UnificationXref
id: 5618271
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618271

SequenceSite630
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref3857
type: UnificationXref
id: 5613536
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613536

UnificationXref1715
type: UnificationXref
id: REACT_252690
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_252690.1

UnificationXref3854
type: UnificationXref
id: REACT_18116
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_18116.1

UnificationXref1716
type: UnificationXref
id: 5618015
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618015

UnificationXref3855
type: UnificationXref
id: P36421
db: UniProt

UnificationXref1710
type: UnificationXref
id: 5611311
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611311

UnificationXref1711
type: UnificationXref
id: REACT_231279
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_231279.1

UnificationXref3858
type: UnificationXref
id: 5613538
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613538

UnificationXref1712
type: UnificationXref
id: 5618270
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618270

UnificationXref3859
type: UnificationXref
id: REACT_220154
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_220154.2

UnificationXref772
type: UnificationXref
id: P0CX38
db: UniProt

UnificationXref3853
type: UnificationXref
id: 379785
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379785

UnificationXref773
type: UnificationXref
id: 5609378
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609378

UnificationXref3852
type: UnificationXref
id: CHEBI:29161
db: ChEBI

UnificationXref770
type: UnificationXref
id: 5609228
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609228

UnificationXref3851
type: UnificationXref
id: REACT_23144
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_23144.1

UnificationXref771
type: UnificationXref
id: 5609229
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609229

UnificationXref3850
type: UnificationXref
id: 379743
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379743

UnificationXref776
type: UnificationXref
id: 5609381
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609381

UnificationXref777
type: UnificationXref
id: P05756
db: UniProt

UnificationXref774
type: UnificationXref
id: P0CX37
db: UniProt

UnificationXref775
type: UnificationXref
id: 5609380
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609380

UnificationXref778
type: UnificationXref
id: 5609198
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609198

SequenceSite629
type: SequenceSite
position status: EQUAL
sequence position: 427

http://identifiers.org/pubmed/8541526
type: PublicationXref
id: 8541526
author: Park, JG
author: Hunter, S
author: Schreiber, AD
author: Indik, ZK
db: Pubmed
title: The molecular dissection of Fc gamma receptor mediated phagocytosis
source: Blood 86:4389-99
year: 1995

UnificationXref779
type: UnificationXref
id: P05750
db: UniProt

SequenceSite628
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite624
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite625
type: SequenceSite
position status: EQUAL
sequence position: 692

SequenceSite626
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite627
type: SequenceSite
position status: EQUAL
sequence position: 1312

UnificationXref1708
type: UnificationXref
id: 5611304
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611304

SequenceSite620
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref1709
type: UnificationXref
id: 5611310
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611310

SequenceSite621
type: SequenceSite
position status: EQUAL
sequence position: 345

UnificationXref1706
type: UnificationXref
id: 5611308
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611308

SequenceSite622
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref1707
type: UnificationXref
id: P26309
db: UniProt

SequenceSite623
type: SequenceSite
position status: EQUAL
sequence position: 854

UnificationXref1704
type: UnificationXref
id: REACT_249037
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_249037.1

UnificationXref3843
type: UnificationXref
id: REACT_17447
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_17447.1

UnificationXref1705
type: UnificationXref
id: P40958
db: UniProt

UnificationXref3844
type: UnificationXref
id: Q12109
db: UniProt

UnificationXref1702
type: UnificationXref
id: REACT_201908
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_201908.2

UnificationXref3845
type: UnificationXref
id: 5613528
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613528

http://identifiers.org/pubmed/9771708
type: PublicationXref
id: 9771708
author: Ahmad, W
author: Swank, RT
author: Krakow, D
author: King, LM
author: Cohn, DH
author: Abbas, H
author: Ahmad, M
author: Rusiniak, ME
author: Superti-Furga, A
author: Cantor, RM
author: ul Haque, MF
author: Haque, S
db: Pubmed
title: Mutations in orthologous genes in human spondyloepimetaphyseal dysplasia and the brachymorphic mouse
source: Nat Genet 20:157-62
year: 1998

UnificationXref1703
type: UnificationXref
id: 5618018
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618018

UnificationXref3846
type: UnificationXref
id: 5613529
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613529

UnificationXref1700
type: UnificationXref
id: REACT_220102
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_220102.2

UnificationXref3847
type: UnificationXref
id: 5613531
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613531

UnificationXref1701
type: UnificationXref
id: 5618017
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618017

UnificationXref3848
type: UnificationXref
id: REACT_216070
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_216070.2

UnificationXref3849
type: UnificationXref
id: CHEBI:29182
db: ChEBI

http://identifiers.org/pubmed/8631325
type: PublicationXref
id: 8631325
author: Peng, HL
author: Chao, YC
author: Chang, HY
author: Duggleby, RG
author: Huang, JG
db: Pubmed
title: Sequence differences between human muscle and liver cDNAs for UDPglucose pyrophosphorylase and kinetic properties of the recombinant enzymes expressed in Escherichia coli.
source: Eur J Biochem 235:173-9
year: 1996

UnificationXref3840
type: UnificationXref
id: REACT_15882
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15882.1

UnificationXref760
type: UnificationXref
id: 5609327
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609327

UnificationXref761
type: UnificationXref
id: 5609328
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609328

UnificationXref3842
type: UnificationXref
id: 379765
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379765

UnificationXref762
type: UnificationXref
id: P0CX35
db: UniProt

UnificationXref3841
type: UnificationXref
id: CHEBI:29159
db: ChEBI

UnificationXref763
type: UnificationXref
id: 5609365
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609365

UnificationXref764
type: UnificationXref
id: P0CX36
db: UniProt

UnificationXref765
type: UnificationXref
id: 5609367
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609367

UnificationXref766
type: UnificationXref
id: 5609368
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609368

UnificationXref767
type: UnificationXref
id: P02407
db: UniProt

SequenceSite618
type: SequenceSite
position status: EQUAL
sequence position: 1

http://identifiers.org/pubmed/9771710
type: PublicationXref
id: 9771710
author: Snead, O Carter
author: Andermann, Eva
author: Dunham, Ian
author: Fong, Chung-yan G
author: Soder, Sylvia
author: Tsui, LC
author: Satishchandra, P
author: Scherer, Stephen W
author: Jardim, L
author: Huizenga, Jack
author: Delgado-Escueta, Antonio V
author: Gardner, Rebecca
author: Lopes-Cendes, Iscia
author: Lee, Jeffrey R
author: Minassian, Berge A
author: Mungall, Andrew J
author: Herbrick, Jo-Anne
author: Rouleau, Guy A
author: Carpenter, Stirling
db: Pubmed
title: Mutations in a gene encoding a novel protein tyrosine phosphatase cause progressive myoclonus epilepsy
source: Nat. Genet. 20:171-4
year: 1998

UnificationXref768
type: UnificationXref
id: 5609224
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609224

SequenceSite617
type: SequenceSite
position status: EQUAL
sequence position: 636

UnificationXref769
type: UnificationXref
id: P14127
db: UniProt

SequenceSite619
type: SequenceSite
position status: EQUAL
sequence position: 398

UnificationXref8048
type: UnificationXref
id: CHEBI:29017
db: ChEBI

UnificationXref713
type: UnificationXref
id: 5609458
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609458

SequenceSite606
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref8049
type: UnificationXref
id: 1498738
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1498738

UnificationXref712
type: UnificationXref
id: REACT_4829
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4829.1

SequenceSite607
type: SequenceSite
position status: EQUAL
sequence position: 145

UnificationXref715
type: UnificationXref
id: 5609422
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609422

SequenceSite608
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref714
type: UnificationXref
id: P40217
db: UniProt

SequenceSite609
type: SequenceSite
position status: EQUAL
sequence position: 83

UnificationXref711
type: UnificationXref
id: 72393
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72393

UnificationXref710
type: UnificationXref
id: 5609457
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609457

UnificationXref8040
type: UnificationXref
id: CHEBI:45360
db: ChEBI

UnificationXref8041
type: UnificationXref
id: 1500661
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1500661

UnificationXref8042
type: UnificationXref
id: REACT_122049
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_122049.1

UnificationXref8043
type: UnificationXref
id: 5616248
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616248

UnificationXref8044
type: UnificationXref
id: 5616250
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616250

UnificationXref8045
type: UnificationXref
id: REACT_181254
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_181254.3

UnificationXref8046
type: UnificationXref
id: 5618597
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618597

UnificationXref8047
type: UnificationXref
id: REACT_188974
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_188974.3

UnificationXref8050
type: UnificationXref
id: REACT_123106
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_123106.1

SequenceSite610
type: SequenceSite
position status: EQUAL
sequence position: 1

http://identifiers.org/pubmed/20945529
type: PublicationXref
id: 20945529
author: Sistonen, Lea
author: Björk, Johanna K
db: Pubmed
title: Regulation of the members of the mammalian heat shock factor family
source: FEBS J. 277:4126-39
year: 2010

http://identifiers.org/pubmed/19443651
type: PublicationXref
id: 19443651
author: Wang, Jianghai
author: Fukui, Lisa
author: Lee, Brian
author: Cai, Sheng
author: Chen, Yuan
author: Hu, Weidong
db: Pubmed
title: Conformational transition associated with E1-E2 interaction in small ubiquitin-like modifications
source: J. Biol. Chem. 284:20340-8
year: 2009

SequenceSite612
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite611
type: SequenceSite
position status: EQUAL
sequence position: 83

UnificationXref716
type: UnificationXref
id: P06103
db: UniProt

SequenceSite614
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref717
type: UnificationXref
id: 5609430
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609430

SequenceSite613
type: SequenceSite
position status: EQUAL
sequence position: 133

UnificationXref718
type: UnificationXref
id: P38249
db: UniProt

SequenceSite616
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref719
type: UnificationXref
id: 5609434
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609434

SequenceSite615
type: SequenceSite
position status: EQUAL
sequence position: 133

UnificationXref8039
type: UnificationXref
id: 5616247
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616247

UnificationXref704
type: UnificationXref
id: 5609447
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609447

UnificationXref703
type: UnificationXref
id: P20459
db: UniProt

UnificationXref8037
type: UnificationXref
id: P39006
db: UniProt

UnificationXref702
type: UnificationXref
id: REACT_2875
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2875.1

UnificationXref8038
type: UnificationXref
id: 5616246
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616246

UnificationXref701
type: UnificationXref
id: 29438
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29438

UnificationXref700
type: UnificationXref
id: 5609443
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609443

UnificationXref8031
type: UnificationXref
id: REACT_260726
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_260726.1

UnificationXref8032
type: UnificationXref
id: CHEBI:18303
db: ChEBI

UnificationXref8030
type: UnificationXref
id: 5616154
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616154

UnificationXref8035
type: UnificationXref
id: 1524083
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1524083

UnificationXref8036
type: UnificationXref
id: REACT_124336
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_124336.1

UnificationXref8033
type: UnificationXref
id: 1500644
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1500644

UnificationXref8034
type: UnificationXref
id: REACT_123472
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_123472.1

http://identifiers.org/pubmed/20945530
type: PublicationXref
id: 20945530
author: Enoki, Yasuaki
author: Sakurai, Hiroshi
db: Pubmed
title: Novel aspects of heat shock factors: DNA recognition, chromatin modulation and gene expression
source: FEBS J. 277:4140-9
year: 2010

http://identifiers.org/pubmed/16738315
type: PublicationXref
id: 16738315
author: Lee, Hsiang-Ying
author: Gill, Grace
author: Catic, Andre
author: Di Bacco, A
author: Ouyang, Jian
author: Ploegh, Hidde
db: Pubmed
title: The SUMO-specific protease SENP5 is required for cell division
source: Mol. Cell. Biol. 26:4489-98
year: 2006

http://identifiers.org/pubmed/19957260
type: PublicationXref
id: 19957260
author: Lambert, DM
author: Ferrer, JL
author: Bauvois, C
author: Wouters, J
author: Borel, F
author: Labar, G
db: Pubmed
title: Crystal structure of the human monoacylglycerol lipase, a key actor in endocannabinoid signaling
source: Chembiochem 11:218-27
year: 2010

SequenceSite601
type: SequenceSite
position status: EQUAL
sequence position: 264

SequenceSite600
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref709
type: UnificationXref
id: 5609456
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609456

UnificationXref707
type: UnificationXref
id: P09064
db: UniProt

SequenceSite605
type: SequenceSite
position status: EQUAL
sequence position: 152

UnificationXref708
type: UnificationXref
id: 5609451
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609451

SequenceSite604
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref705
type: UnificationXref
id: P32481
db: UniProt

SequenceSite603
type: SequenceSite
position status: EQUAL
sequence position: 152

UnificationXref706
type: UnificationXref
id: 5609455
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609455

SequenceSite602
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref731
type: UnificationXref
id: 5609176
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609176

UnificationXref730
type: UnificationXref
id: Q08745
db: UniProt

UnificationXref733
type: UnificationXref
id: 5609180
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609180

UnificationXref732
type: UnificationXref
id: P46784
db: UniProt

UnificationXref8026
type: UnificationXref
id: P17898
db: UniProt

UnificationXref735
type: UnificationXref
id: P0CX33
db: UniProt

UnificationXref8027
type: UnificationXref
id: 5616150
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616150

UnificationXref734
type: UnificationXref
id: 5609181
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609181

UnificationXref8028
type: UnificationXref
id: 5616151
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616151

UnificationXref737
type: UnificationXref
id: P0CX34
db: UniProt

UnificationXref8029
type: UnificationXref
id: 5616152
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616152

UnificationXref736
type: UnificationXref
id: 5609347
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609347

UnificationXref8022
type: UnificationXref
id: 5616143
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616143

UnificationXref8023
type: UnificationXref
id: P22140
db: UniProt

UnificationXref8024
type: UnificationXref
id: 5616142
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616142

UnificationXref8025
type: UnificationXref
id: 5616144
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616144

UnificationXref8020
type: UnificationXref
id: 1500595
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1500595

UnificationXref8021
type: UnificationXref
id: REACT_122641
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_122641.1

http://identifiers.org/pubmed/15153069
type: PublicationXref
id: 15153069
author: Lake, S
author: Climent, I
author: Swiezewska, E
author: Forsgren, M
author: Attersand, A
author: Dallner, G
author: Grünler, J
db: Pubmed
title: Isolation and functional expression of human COQ2, a gene encoding a polyprenyl transferase involved in the synthesis of CoQ
source: Biochem J 382:519-26
year: 2004

http://identifiers.org/pubmed/11681785
type: PublicationXref
id: 11681785
author: Hruz, PW
author: Mueckler, MM
db: Pubmed
title: Structural analysis of the GLUT1 facilitative glucose transporter (review).
source: Mol Membr Biol 18:183-93
year: 2001

UnificationXref738
type: UnificationXref
id: 5609349
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609349

UnificationXref739
type: UnificationXref
id: 5609350
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609350

UnificationXref722
type: UnificationXref
id: Q04067
db: UniProt

UnificationXref721
type: UnificationXref
id: 5609438
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609438

UnificationXref8019
type: UnificationXref
id: REACT_124951
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_124951.1

UnificationXref720
type: UnificationXref
id: P32497
db: UniProt

UnificationXref8017
type: UnificationXref
id: CHEBI:16038
db: ChEBI

UnificationXref726
type: UnificationXref
id: 5609251
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609251

UnificationXref8018
type: UnificationXref
id: 1500581
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1500581

UnificationXref725
type: UnificationXref
id: Q3E7Y3
db: UniProt

UnificationXref8015
type: UnificationXref
id: 5616242
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616242

UnificationXref724
type: UnificationXref
id: 5609439
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609439

UnificationXref8016
type: UnificationXref
id: REACT_181233
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_181233.3

UnificationXref723
type: UnificationXref
id: 5609426
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609426

UnificationXref8013
type: UnificationXref
id: 5616239
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616239

UnificationXref8014
type: UnificationXref
id: 5616240
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616240

UnificationXref8011
type: UnificationXref
id: 5616237
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616237

UnificationXref8012
type: UnificationXref
id: 5616238
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616238

http://identifiers.org/pubmed/18555844
type: PublicationXref
id: 18555844
author: Buehrer, B
author: Madan, AK
author: Fain, JN
author: Bahouth, SW
author: Tichansky, DS
db: Pubmed
title: Comparison of messenger RNA distribution for 60 proteins in fat cells vs the nonfat cells of human omental adipose tissue
source: Metabolism 57:1005-15
year: 2008

UnificationXref8010
type: UnificationXref
id: 5616236
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616236

http://identifiers.org/pubmed/15276077
type: PublicationXref
id: 15276077
author: Chimienti, F
author: Seve, M
author: Favier, A
author: Coquerel, Y
author: Pennequin, A
author: Devergnas, S
author: Naud, N
author: Chantegrel, J
db: Pubmed
title: Differential regulation of zinc efflux transporters ZnT-1, ZnT-5 and ZnT-7 gene expression by zinc levels: a real-time RT-PCR study
source: Biochem Pharmacol 68:699-709
year: 2004

http://identifiers.org/pubmed/17266529
type: PublicationXref
id: 17266529
author: Hyde, JE
db: Pubmed
title: Targeting purine and pyrimidine metabolism in human apicomplexan parasites
source: Curr Drug Targets 8:31-47
year: 2007

UnificationXref729
type: UnificationXref
id: 5609256
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609256

UnificationXref727
type: UnificationXref
id: P0C0W1
db: UniProt

UnificationXref728
type: UnificationXref
id: 5609255
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609255

http://identifiers.org/pubmed/12700044
type: PublicationXref
id: 12700044
author: Maness, PF
author: Thelen, K
author: Panicker, AK
author: Buhusi, M
db: Pubmed
title: Cellular signalling mechanisms of neural cell adhesion molecules
source: Front Biosci 8:d900-11
year: 2003

UnificationXref8001
type: UnificationXref
id: 1500603
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1500603

Evidence701
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18597486
comment: Reactions for the synthesis of the small nucleotide-linked sugar substrates that are used in the synthesis of the N-glycan precursor and in the later steps of glycosylation are annotated here. All these nucleotide-linked sugar donors are synthesized in the cytosol; however, to participate in the later reactions of N-glycan precursor biosynthesis (when the glycan is oriented toward the lumen of the endoplasmic reticulum (ER)), these substrates must be attached to a dolichyl-phosphate molecule and then flipped toward the luminal side of the ER, through a mechanism which is still not known but which involves a different protein than the one that mediates the flipping of the LLO itself (Sanyal et al. 2008). Two of the genes encoding enzymes involved in these reactions, MPI and PMM2, are known to be associated with Congenital Disorders of Glycosylation (CDG) diseases of type I. Of these, CDG-Ia, associated with defects in PMM2, is the most frequent CDG disease reported.

UnificationXref8000
type: UnificationXref
id: CHEBI:16732
db: ChEBI

Evidence700
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Dolichyl-phosphate-glucose functions as a donor of glucose groups in reactions including three steps of N-glycan precursor biosynthesis. Dolichyl-phosphate-glucose itself is synthesized from UDP-glucose and dolichol phosphate on the cytosolic face of the endoplasmic reticulum membrane, then flipped to the luminal surface of that membrane.

UnificationXref8003
type: UnificationXref
id: P33412
db: UniProt

Evidence703
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16100110
comment: A second N-acetylglucosamine is added to the N-glycan precursor via a beta-1,4 linkage. This reaction is catalyzed by the ALG13:ALG14 complex, in which ALG13 functions as the catalyst and ALG14 functions as a membrane anchor which recruits ALG13 to the cytosolic face of ER (Gao XD et al, 2005).

UnificationXref8002
type: UnificationXref
id: REACT_124825
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_124825.1

Evidence702
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12872255
xref: http://identifiers.org/pubmed/9451016
comment: In the first step of N-glycan precursor (LLO) synthesis, N-acetylglucosamine is added, via an alpha-1,3 linkage, to a molecule of dolichyl phosphate, producing N-acetyl-D-glucosaminyl-diphosphodolichol (Eckert et al. 1998). This reaction is catalyzed by DPAGT1 (ALG7 in yeast), mutations in which are associated with CDG disorder type I-J (Wu et al. 2003). The dolichyl phosphate acts as an anchor for the LLO, so that subsequent sugar-addition reactions take place on a sugar anchored in the ER membrane.

UnificationXref8005
type: UnificationXref
id: 5616233
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616233

UnificationXref8004
type: UnificationXref
id: 5616232
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616232

UnificationXref8007
type: UnificationXref
id: REACT_181237
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_181237.3

UnificationXref8006
type: UnificationXref
id: 5616235
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616235

UnificationXref8009
type: UnificationXref
id: REACT_14559
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_14559.2

UnificationXref8008
type: UnificationXref
id: 217314
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=217314

Evidence704
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/14709599
xref: http://identifiers.org/pubmed/14973782
xref: http://identifiers.org/pubmed/14973778
xref: http://identifiers.org/pubmed/10704531
comment: A mannose is added to the N-glycan precursor via a beta-1,4 linkage. The reaction is catalyzed by ALG1 (Takahashi T et al, 2000). Defects in ALG1 lead to congenital disorder of glycosylation type 1K (CDG1K) (Schwarz et al. 2004; Kranz et al. 2004; Grubenmann et al. 2004).

Evidence705
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12684507
comment: A second mannose is added to the N-glycan precursor via an alpha-1,3 linkage. The reaction is catalyzed by the mannosyltransferase ALG2. This is a bifunctional enzyme with both alpha 1,3- and alpha 1,6-mannosyltransferase activities. In humans, only the alpha 1,3 activity used in this reaction has been elucidated (Thiel et al. 2003). Defects in ALG2 are the cause of ALG2-CDG (CDG-1i; MIM:607906) (Thiel et al. 2003).

Evidence706
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12684507
xref: http://identifiers.org/pubmed/19282279
xref: http://identifiers.org/pubmed/16878994
comment: A third mannose is added to the N-glycan precursor by ALG2 using its alpha1,6-mannosyltransferase activity. This has been demonstrated experimentally in yeast (O'Reilly MK et al, 2006; Kämpf M et al, 2009); the human reaction is inferred by homology. Defects in ALG2 are the cause for CDG1I (Thiel C et al, 2003).

Evidence707
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11278778
comment: A fourth mannose is added to the N-glycan precursor by ALG11. The addition of the fifth mannose, also by ALG11, is the last step occurring on the cytosolic side of the ER membrane (Cipollo JF et al, 2001). Both these reactions are alpha1,2 mannose additions.

Evidence708
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11807558
xref: http://identifiers.org/pubmed/18313027
xref: http://identifiers.org/pubmed/18597486
comment: The precursor of the N-glycan sugar, now in the form of (GlcNAc)2 (Man)5 (PP-Dol), is flipped across the ER membrane, moving it from the cytosolic side into the ER lumen. The exact mechanism of this translocation is not well understood: the protein RFT1 is known to be involved (Helenius et al. 2002), along with an unknown flippase, which is distinct from the one that flips the Dol-P linked precursors (Dol-P-Mannose and Dol-P-glucose) (Sanyal et al. 2008). Defects in RFT1 are associated with Congenital Disorder of Glycosylation 1N (CDG1N) (Haeuptle et al. 2008).

Evidence709
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12200473
xref: http://identifiers.org/pubmed/15840742
comment: The sixth mannose is added to the N-glycan precursor. This reaction occurs in the ER lumen and uses a different mannose donor (dolichyl-phosphate-mannose) than the previous steps. It has been proposed that ALG3, along with all the mannosyl- and glucosyltransferases in the N-glycan biosynthesis pathway that use dolichyl-phosphate-mannose or dolichyl-phosphate-glucose as donor, derive from duplications of a common ancestral enzyme (Oriol et al. 2002). Defects in ALG3 are associated with Congenital Disorder of Glycosylation 1D (CDG1D) (Sun et al. 2005).

Evidence710
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15148656
xref: http://identifiers.org/pubmed/16859551
xref: http://identifiers.org/pubmed/15945070
xref: http://identifiers.org/pubmed/12030331
comment: The seventh mannose is added to the N-glycan precursor. This reaction occurs in the ER lumen and uses dolichyl phosphate D-mannose as the mannose donor with ALG9 mediating the reaction. Defects in ALG9 are the cause of congenital disorder of glycosylation type 1L (CDG1L) (Frank CG et al, 2004; Weinstein M et al, 2005). For many years ALG9 has been thought to be involved in bipolar affective disorder (Baysal BE et al, 2002), but this hypothesis has been proven wrong (Baysal BE et al, 2006).

Evidence714
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16007612
xref: http://identifiers.org/pubmed/15235028
comment: The second glucose (supplied from the donor dolichol-phosphate-glucose) is added to the N-glycan precursor, mediated by ALG8 (Schollen E et al, 2004). Defects in ALG8 are the cause of congenital disorder of glycosylation type 1H (CDG1H) (Schollen E et al, 2004; Sun L et al, 2005).

Evidence713
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: PublicationXref1615
xref: http://identifiers.org/pubmed/10359825
comment: The first glucose is added to the N-glycan precursor, mediated by ALG6. Defects in ALG6 are associated with CDG-Ic disorder (Imbach T et al, 1999; Sun L et al, 2005). The donor is a dolichol-phosphate-glucose (synthesized by ALG5).

Evidence712
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15148656
xref: http://identifiers.org/pubmed/16859551
xref: http://identifiers.org/pubmed/15945070
xref: http://identifiers.org/pubmed/12030331
comment: The last mannose is added to the N-glycan precursor. This reaction occurs in the ER lumen, uses Dolichyl phosphate D-mannose as the mannose donor, and is catalyzed by ALG9. Defects in ALG9 are the cause of congenital disorder of glycosylation type 1L (CDG1L) (Frank CG et al, 2004; Weinstein M et al, 2005). For many years ALG9 was thought to be involved in bipolar affective disorder (Baysal BE et al, 2002), but this hypothesis has been proven wrong (Baysal BE et al, 2006).

Evidence711
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11983712
comment: The eighth mannose is added to the N-glycan precursor. This reaction occurs in the ER lumen and uses dolichyl phosphate D-mannose as a mannose donor. Defects in ALG12 are the cause of congenital disorder of glycosylation type 1G (CDG1G) (Chantret I et al, 2002).

http://identifiers.org/pubmed/15538381
type: PublicationXref
id: 15538381
author: Lu, M
author: Gherzi, R
author: Leuenberger, SA
author: Hemmings, BA
author: Stoecklin, G
author: Hess, D
author: Mallaun, M
author: Schmidlin, M
author: Moroni, C
author: Gross, B
db: Pubmed
title: The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B
source: EMBO J 23:4760-9
year: 2004

Evidence717
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10788335
xref: http://identifiers.org/pubmed/12145188
comment: After the glycosylated precursor is attached to the protein, the outer alpha-1,2-linked glucose is removed by glucosidase I (MOGS, GCS1 in yeast). This is a mandatory step for the protein folding control and glycan extension, and defects in MOGS are associated with congenital disorder of glycosylation type IIb (CDGIIb) (De Praeter et al. 2000, Völker et al. 2002).

Evidence718
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16431915
xref: http://identifiers.org/pubmed/10409699
comment: The enzyme ER Man I can slowly trim up to four of the mannoses on the N-glycan on unfolded proteins accumulated in the ER. This step describes the removal of the mannose in the B position (Gonzalez et al, 1999: Hirao et al, 2006).

Evidence715
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15710750
xref: http://identifiers.org/pubmed/9597543
comment: The last glucose is added to the N-glycan precursor. This reaction occurs inside the ER lumen and uses Dol-P-Glc as the glucose donor. In yeast, this reaction is catalyzed by ALG10 (Burda P and Aebi M,1998); however, this gene is duplicated in primates (Ciccarelli FD et al, 2005; Table 1), leading to two homologues, ALG10A and ALG10B, and to date there is no clear evidence to say which of these two paralogues (or both) is responsible for catalyzing this reaction in humans. No Congenital Disorders of Glycosylations are known to be associated with either gene.

Evidence716
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/20301507
comment: N-linked glycosylation commences with the 14-step synthesis of a dolichol lipid-linked oligosaccharide (LLO) consisting of 14 sugars (2 core GlcNAcs, 9 mannoses and 3 terminal GlcNAcs). This pathway is highly conserved in eukaryotes, and a closely related pathway is found in many eubacteria and Archaea. Mutations in the genes associated with N-glycan precursor synthesis lead to a diverse group of disorders collectively known as Congenital Disorders of Glycosylation (type I and II) (Sparks et al. 1993). The phenotypes of these disorders reflect the important role that N-glycosylation has during development, controlling the folding and the properties of proteins in the secretory pathway, and proteins that mediate cell-to-cell interactions or timing of development.

Evidence719
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16431915
comment: The enzyme ER Man I can slowly trim up to four of the mannoses on the N-glycan on unfolded proteins accumulated in the ER. This step describes the removal of the mannose in the C position (Hirao et al, 2006).

Evidence723
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17499246
comment: Proteins with major folding defects are extracted from futile folding cycles in the calnexin chaperone system and the ER Quality Control Compartment, and are translocated back to the citosol for degradation. The N-glycan is used as a signal to distinguish proteins to be degraded, upon recognition by EDEM1, EDEM2 and EDEM3, three ER-stress-induced members of the glycosyl hydrolase 47 family (see Olivari S, Molinari M 2007 for a review) and OS9 (Mikami K, 2010; Hosokawa N, 2009).

Evidence722
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18426978
xref: http://identifiers.org/pubmed/10694380
xref: http://identifiers.org/pubmed/12913004
comment: The enzymes UGGT1 and UGGT2 are able to distinguish proteins with minor folding defects in the ERQC and reglucosylate them, by adding a glucose on the alpha 1,3 branch (Arnold SM et al, 2000; Arnold SM et al, 2003). The major affinity of these enzymes for proteins with minor folding defects has been demonstrated, but the exact mechanism that enable them to distinguish proteins with major and minor defects is still unknown (Pearse BR et al, 2008).

Evidence725
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18337472
xref: http://identifiers.org/pubmed/18303019
comment: The unfolded protein is recognized by a chaperon protein (calnexin or calreticulin) and the folding process starts. The binding of these protein requires a mono-glucosylated glycan (Caramelo JJ and Parodi AJ, 2008), but in certain cases can occur even in the absence of glycosylation (Ireland BS et al, 2008).

Evidence724
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/20347046
xref: http://identifiers.org/pubmed/18003979
xref: http://identifiers.org/pubmed/19616933
xref: http://identifiers.org/pubmed/11408579
comment: Proteins that are released from the CNX or CRT complex with folding defects accumulate in a compartment of the ER called ERQC (Kamhi-Nesher et al. 2001). Here, the enzymes UGGG1 or UGGG2 are able to recognize glycoproteins with minor folding process and re-add the glucose on the alpha,1,3 branch; this is a signal for the transport of these glycoproteins back to the ER, where they can interact again with CNX or CRT in order to achieve a correct folding. At the same time that the glycoprotein is in the ERQC, the enzyme ER mannosidase I progressively removes the mannoses in position 1A, 2A, B, C on N-glycans; when the mannose on 1A is trimmed, UGGG1/UGGG2 is no longer able to re-add the glucose, and therefore the protein is destined for degradation. For years it has been thought that the removal of the mannose in position B of the N-glycan was the signal to direct proteins to degradation. However, this mechanism has been described better by Avezov et al (Avezov et al. 2008) and it has been demonstrated that even glycoproteins with Man8 or Man7 glycans can be re-glucosylated and interact again with CNX or CRT. For a review on this topic, see Lederkremer 2009 and Maattanen P et al, 2010.

Evidence721
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12829701
comment: Removal of the second mannose on the alpha 1,3 branch (Frenzel Z et al, 2003).

Evidence720
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16431915
xref: http://identifiers.org/pubmed/12829701
comment: The enzyme ER Man I can slowly trim up to four of the mannoses on the N-glycan on unfolded proteins accumulated in the ER. This step describes the removal of the mannose in the A position (Hirao et al, 2006; Frenkel et al, 2003).

Evidence726
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: PublicationXref1636
comment: After being synthesized in the ER membrane the 14-sugars lipid-linked oligosaccharide is co-translationally transferred to an unfolded protein, as described in the previous steps. After this point the N-glycan is progressively trimmed of the three glucoses and some of the mannoses before the protein is transported to the cis-Golgi. The role of these trimming reactions is that the N-glycan attached to an unfolded glycoprotein in the ER assume the role of 'tags' that direct the interactions of the glycoprotein with different elements that mediate its folding. The removal of the two outer glucoses leads to an N-glycan with only one glucose, which is a signal for the binding of either one of two chaperone proteins, calnexin (CNX) and calreticulin (CRT). These chaperones provide an environment where the protein can fold more easily. The interaction with these proteins is not transient and is terminated by the trimming of the last remaining glucose, after which the glycoprotein is released from CNX or CRT and directed to the ER Quality Control compartment (ERQC) if it still has folding defects, or transported to the Golgi if the folding is correct. The involvement of N-glycans in the folding quality control of proteins in the ER explains why this form of glycosylation is so important, and why defects in the enzymes involved in these reactions are frequently associated with congenital diseases. However, there are many unknown points in this process, as it is known that even proteins without N-glycosylation sites can be folded properly (Caramelo JJ and Parodi AJ, 2008).

Evidence727
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10825291
xref: http://identifiers.org/pubmed/10982397
comment: Sar1p-GTP recruits the cytoplasmic Sec23p-Sec24p complex. Though not represented in the subsequent steps, Sec23p-Sec24p would bind to members of the p24 protein family of possible cargo receptors, and together with Sar1p bind the appropiate v-SNARE, and Rab-GTP.

Evidence728
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17316621
xref: http://identifiers.org/pubmed/10825291
xref: http://identifiers.org/pubmed/10982397
comment: Sar1p-GTP hydrolysis is increased 15-30-fold by Sec23p. Sar1p-GDP is released as a result of this hydrolysis and used in further vesicle sculpting cycles. Sar1p-GTP hydrolysis occurs at two critical points during the cycle, first (as represented here) as a proofreading step, insuring that the cargo is loaded. Later in the cycle Sar1p-GTP hydrolysis triggers the uncoating of the budded vesicle.

http://identifiers.org/pubmed/11907280
type: PublicationXref
id: 11907280
author: Hagting, A
author: Pines, J
author: Jackman, M
author: Kubota, Y
author: Den Elzen, N
db: Pubmed
title: Cyclin A- and cyclin E-Cdk complexes shuttle between the nucleus and the cytoplasm
source: Mol Biol Cell 13:1030-45
year: 2002

Evidence729
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10825291
xref: http://identifiers.org/pubmed/10982397
comment: Cytosolic Sec13p-Sec31p complexes bind to pre-bound Sec23p-Sec24p complexes.

Evidence736
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16738331
xref: http://identifiers.org/pubmed/15487983
xref: http://identifiers.org/pubmed/12192048
xref: http://identifiers.org/pubmed/17591783
xref: http://identifiers.org/pubmed/16253240
xref: http://identifiers.org/pubmed/11896061
xref: http://identifiers.org/pubmed/14563852
comment: The SUMO1 precursor has 4 extra residues at the C-terminus which can be removed endoproteolytically by either SENP1, SENP2, or SENP5 (Zheng and Au, 2005, Mikolajczyk et al. 2007). The order of processing activity is: SENP1 greater than SENP2 greater than SENP5 (Mikolajczyk et al. 2007). Both SENP1 and SENP2 shuttle between the nucleus and cytoplasmic and both are predominantly nucleoplasmic (Bailey and O'Hare 2004, Kim et al. 2005, Zhang et al. 2002, Hang and Dasso 2002, Itahana et al. 2006).

Evidence735
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16807922
xref: http://identifiers.org/pubmed/10580125
xref: http://identifiers.org/pubmed/20301507
xref: http://identifiers.org/pubmed/20301244
xref: http://identifiers.org/pubmed/19616933
xref: http://identifiers.org/pubmed/19647993
comment: N-linked glycosylation is the most important form of post-translational modification for proteins synthesized and folded in the Endoplasmic Reticulum (Stanley et al. 2009). An early study in 1999 revealed that about 50% of the proteins in the Swiss-Prot database at the time were N-glycosylated (Apweiler et al. 1999). It is now established that the majority of the proteins in the secretory pathway require glycosylation in order to achieve proper folding. The addition of an N-glycan to a protein can have several roles (Shental-Bechor & Levy 2009). First, glycans enhance the solubility and stability of the proteins in the ER, the golgi and on the outside of the cell membrane, where the composition of the medium is strongly hydrophilic and where proteins, that are mostly hydrophobic, have difficulty folding properly. Second, N-glycans are used as signal molecules during the folding and transport process of the protein: they have the role of labels to determine when a protein must interact with a chaperon, be transported to the golgi, or targeted for degradation in case of major folding defects. Third, and most importantly, N-glycans on completely folded proteins are involved in a wide range of processes: they help determine the specificity of membrane receptors in innate immunity or in cell-to-cell interactions, they can change the properties of hormones and secreted proteins, or of the proteins in the vesicular system inside the cell. All N-linked glycans are derived from a common 14-sugar oligosaccharide synthesized in the ER, which is attached co-translationally to a protein while this is being translated inside the reticulum. The process of the synthesis of this glycan, known as Synthesis of the N-glycan precursor or LLO, constitutes one of the most conserved pathways in eukaryotes, and has been also observed in some eubacteria. The attachment usually happens on an asparagine residue within the consensus sequence asparagine-X-threonine by an complex called oligosacc…

http://identifiers.org/pubmed/10448521
type: PublicationXref
id: 10448521
author: Seetharam, B
db: Pubmed
title: Receptor-mediated endocytosis of cobalamin (vitamin B12)
source: Annu. Rev. Nutr. 19:173-95
year: 1999

Evidence734
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10412983
xref: http://identifiers.org/pubmed/3594573
xref: http://identifiers.org/pubmed/12717434
comment: At least two mechanisms of transport of proteins from the ER to the Golgi have been described. One is a general flow requiring no export signals (Wieland et al, 1987; Marti­nez-Menarguez et al, 1999). The other is mediated by LMAN1/MCFD2, mannose-binding lectins that recognize a glycan signal (Zhang B et al, 2003).

Evidence733
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11252894
comment: Secretory cargo destined to be secreted or to arrive at the plasma membrane (PM) leaves the ER via distinct exit sites. This cargo is destined for the Golgi apparatus.

Evidence732
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17316621
xref: http://identifiers.org/pubmed/11252894
comment: COPII components (known as Sec13p, Sec23p, Sec24p, Sec31p, and Sar1p in yeast) traffic cargo from the endoplasmic reticulum to the Golgi apparatus. COPII-coated vesicles were originally discovered in the yeast Saccharomyces cerevisiae using genetic approaches coupled with a cell-free assay. The mammalian counterpart of this pathway is represented here. Newly synthesized proteins destined for secretion are sorted into COPII-coated vesicles at specialized regions of the ER. These vesicles leave the ER, become uncoated and subsequently fuse with the Golgi apparatus membrane.

Evidence731
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17316621
xref: http://identifiers.org/pubmed/10825291
xref: http://identifiers.org/pubmed/10982397
comment: Vesicle uncoating is triggered by Sar1p-GTP hydrolysis leaving only the vesicle cargo and the v-SNARE to target the vesicle to the Golgi membrane.

Evidence730
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10825291
xref: http://identifiers.org/pubmed/10982397
comment: Once loaded the vesicles become fully sculpted, pinch off from the ER and bud into the cytosol.

http://identifiers.org/pubmed/9335335
type: PublicationXref
id: 9335335
author: Bell, SP
author: Aparicio, OM
author: Weinstein, DM
db: Pubmed
title: Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase.
source: Cell 91:59-69
year: 1997

http://identifiers.org/pubmed/16738331
type: PublicationXref
id: 16738331
author: Itahana, Yoko
author: Yeh, Edward T H
author: Zhang, Yanping
db: Pubmed
title: Nucleocytoplasmic shuttling modulates activity and ubiquitination-dependent turnover of SUMO-specific protease 2
source: Mol. Cell. Biol. 26:4675-89
year: 2006

Evidence739
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16738315
xref: http://identifiers.org/pubmed/16608850
xref: http://identifiers.org/pubmed/19923268
xref: http://identifiers.org/pubmed/20462400
xref: http://identifiers.org/pubmed/21102611
xref: http://identifiers.org/pubmed/16738331
xref: http://identifiers.org/pubmed/12192048
xref: http://identifiers.org/pubmed/17591783
xref: http://identifiers.org/pubmed/20674646
xref: http://identifiers.org/pubmed/16253240
xref: http://identifiers.org/pubmed/11896061
xref: http://identifiers.org/pubmed/14563852
comment: SUMO1, 2, and 3 are initially expressed as propeptides containing extra residues at the C-terminus. (SUMO1 has 4 residues, SUMO2 has 2 residues, and SUMO3 has 11 residues,) SENP1, 2, and 5 are endoproteases that process the precursors to produce the mature peptides (reviewed in Wang and Dasso 2009, Wilkinson and Henley 2010, Hannoun et al. 2010, Gareau and Lima 2010). SENP1 processes SUMO1 with greater efficiency than SUMO2 or SUMO3. SENP2 and SENP5 process SUMO2 with greater efficiency than SUMO1 or SUMO3 (Gong and Yeh 2006, Mikolajczyk et al. 2007). SENP1 shuttles between the cytosol and nuceoplasm and is predominantly nuclear (Bailey and O'hare 2004, Kim et al. 2005). SENP2 also shuttles (Itahana et al. 2006) and is mainly located on nucleoplasmic filaments of the nuclear pore complex (Hang and Dasso 2002, Zhang et al. 2002). SENP5 is located mostly in the nucleolus (Di Bacco et al. 2006, Gong and Yeh 2006).

Evidence737
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16738315
xref: http://identifiers.org/pubmed/16608850
xref: http://identifiers.org/pubmed/16738331
xref: http://identifiers.org/pubmed/15487983
xref: http://identifiers.org/pubmed/12192048
xref: http://identifiers.org/pubmed/17591783
xref: http://identifiers.org/pubmed/16253240
xref: http://identifiers.org/pubmed/11896061
xref: http://identifiers.org/pubmed/14563852
comment: The SUMO2 precursor has 2 extra residues at the C-terminus which can be removed endoproteolytically by SENP1, SENP2, or SENP5 (Zheng and Au, 2005, Gong and Yeh 2006, Mikolajczyk et al. 2007). The order of processing activity is: SENP1 greater than SENP2 greater than SENP5 (Mikolajczyk et al. 2007). SENP2 and SENP5 have highest activity on SUMO2, however the processing activity of SENP1 is higher overall (Mikolajczyk et al. 2007). SENP1 and SENP2 shuttle between the nucleus and cytosol and are predominantly nuclear (Bailey and O'Hare 2004, Kim et al. 2005, Zhang et al. 2002, Hang and Dasso 2002, Itahana et al. 2006). SENP5 is located in the nucleolus (Di Bacco et al. 2006, Gong and Yeh 2006).

Evidence738
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16738315
xref: http://identifiers.org/pubmed/16608850
xref: http://identifiers.org/pubmed/16738331
xref: http://identifiers.org/pubmed/15487983
xref: http://identifiers.org/pubmed/12192048
xref: http://identifiers.org/pubmed/17591783
xref: http://identifiers.org/pubmed/16253240
xref: http://identifiers.org/pubmed/11896061
xref: http://identifiers.org/pubmed/14563852
comment: The SUMO3 precursor has 11 extra residues at the C-terminus which can be removed endoproteolytically by SENP1, SENP2, or SENP5 (Zheng and Au, 2005, Gong and Yeh 2006, Mikolajczyk et al. 2007). The order of processing activity is: SENP1 greater than SENP2 greater than SENP5 (Mikolajczyk et al. 2007). Overall, processing of SUMO3 is the lowest of any SUMO (Mikolajczyk et al. 2007). SENP1 and SENP2 shuttle between the nucleus and cytosol and are predominantly nuclear (Bailey and O'Hare 2004, Kim et al. 2005, Zhang et al. 2002, Hang and Dasso 2002, Itahana et al. 2006). SENP5 is located in the nucleolus (Di Bacco et al. 2006, Gong and Yeh 2006).

http://identifiers.org/pubmed/7564244
type: PublicationXref
id: 7564244
author: Mooyer, P
author: Wanders, RJ
db: Pubmed
title: D-2-hydroxyglutaric acidaemia: identification of a new enzyme, D-2-hydroxyglutarate dehydrogenase, localized in mitochondria
source: J Inherit Metab Dis 18:194-6
year: 1995

http://identifiers.org/pubmed/15317809
type: PublicationXref
id: 15317809
author: Van Remmen, Holly
author: Muller, Florian L
author: Liu, Yuhong
db: Pubmed
title: Complex III releases superoxide to both sides of the inner mitochondrial membrane
source: J. Biol. Chem. 279:49064-73
year: 2004

http://identifiers.org/pubmed/10501970
type: PublicationXref
id: 10501970
author: Francomano, CA
author: Munnich, A
author: King, LM
author: Wilkin, DJ
author: Clarke, CF
author: Ho, N
author: Jonassen, T
author: Vajo, Z
db: Pubmed
title: Conservation of the Caenorhabditis elegans timing gene clk-1 from yeast to human: a gene required for ubiquinone biosynthesis with potential implications for aging
source: Mamm Genome 10:1000-4
year: 1999

http://identifiers.org/pubmed/15280035
type: PublicationXref
id: 15280035
author: Kissner, Reinhard
author: Nauser, Thomas
author: Koppenol, Willem H
author: Vander Stricht, Delphine
author: Clippe, André
author: Dubuisson, Marlène
author: Etienne, Florence
author: Rees, Jean-François
author: Knoops, Bernard
db: Pubmed
title: Human peroxiredoxin 5 is a peroxynitrite reductase
source: FEBS Lett. 571:161-5
year: 2004

http://identifiers.org/pubmed/10970868
type: PublicationXref
id: 10970868
author: Bell, SP
author: Klemm, RD
author: Lee, DG
author: Makhov, AM
db: Pubmed
title: Regulation of origin recognition complex conformation and ATPase activity: differential effects of single-stranded and double-stranded DNA binding.
source: EMBO J 19:4774-82
year: 2000

http://identifiers.org/pubmed/15519848
type: PublicationXref
id: 15519848
author: Reissmann, S
author: Meyer, AS
author: Frydman, J
author: Spiess, C
db: Pubmed
title: Mechanism of the eukaryotic chaperonin: protein folding in the chamber of secrets
source: Trends Cell Biol 14:598-604
year: 2004

http://identifiers.org/pubmed/12482854
type: PublicationXref
id: 12482854
author: Horton, JD
author: Moon, YA
db: Pubmed
title: Identification of two mammalian reductases involved in the two-carbon fatty acyl elongation cascade
source: J Biol Chem 278:7335-43
year: 2003

http://identifiers.org/pubmed/9712840
type: PublicationXref
id: 9712840
author: Kikuchi, Y
author: Mizutani, M
author: Katada, T
author: Imai, M
author: Hoshino, S
author: Hanaoka, F
author: Ui, M
db: Pubmed
title: Molecular cloning of a novel member of the eukaryotic polypeptide chain-releasing factors (eRF). Its identification as eRF3 interacting with eRF1.
source: J Biol Chem 273:22254-9
year: 1998

http://identifiers.org/pubmed/15534001
type: PublicationXref
id: 15534001
author: Allison, JG
author: Williams, CC
author: Beckman, BS
author: Jones, FE
author: Vidal, GA
author: Burow, ME
author: Marrero, L
db: Pubmed
title: The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone
source: J Cell Biol 167:469-78
year: 2004

http://identifiers.org/pubmed/12445824
type: PublicationXref
id: 12445824
author: Ganapathy, V
author: Inoue, K
author: Zhuang, L
db: Pubmed
title: Human Na+ -coupled citrate transporter: primary structure, genomic organization, and transport function
source: Biochem Biophys Res Commun 299:465-71
year: 2002

http://identifiers.org/pubmed/12445829
type: PublicationXref
id: 12445829
author: Visser, WF
author: van Roermund, CW
author: Waterham, HR
author: Wanders, RJ
db: Pubmed
title: Identification of human PMP34 as a peroxisomal ATP transporter
source: Biochem Biophys Res Commun 299:494-7
year: 2002

herbimycin
type: SmallMoleculeReference
name: herbimycin [ChEBI:5674]
xref: UnificationXref5821

http://identifiers.org/pubmed/9587028
type: PublicationXref
id: 9587028
author: Fowler, B
db: Pubmed
title: Genetic defects of folate and cobalamin metabolism
source: Eur. J. Pediatr. 157:S60-6
year: 1998

O2/CO2 exchange in erythrocytes
type: Pathway
data source: Provenance1
pathway component: REACT 202272.2
pathway component: REACT 206424.2
evidence: Evidence1637
xref: RelationshipXref1353
xref: UnificationXref10596
xref: UnificationXref10595
pathway order: PathwayStep1618
pathway order: PathwayStep1620
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

http://identifiers.org/pubmed/11896061
type: PublicationXref
id: 11896061
author: Hang, Jun
author: Dasso, Mary
db: Pubmed
title: Association of the human SUMO-1 protease SENP2 with the nuclear pore
source: J. Biol. Chem. 277:19961-6
year: 2002

Hexose transport
type: Pathway
data source: Provenance1
pathway component: REACT 260359.1
pathway component: BiochemicalReaction472
pathway component: BiochemicalReaction471
evidence: Evidence919
xref: UnificationXref6109
xref: RelationshipXref538
xref: UnificationXref6110
pathway order: PathwayStep895
pathway order: PathwayStep894
pathway order: PathwayStep903
display name: Hexose uptake
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

http://identifiers.org/pubmed/12474143
type: PublicationXref
id: 12474143
author: Carlson, Christopher G
author: Hoffbuhr, Kristen C
author: Kennaway, Nancy G
author: Glerum, D Moira
author: Antonicka, Hana
author: Leary, Scot C
author: Shoubridge, EA
author: Mattman, Andre
db: Pubmed
title: Mutations in COX15 produce a defect in the mitochondrial heme biosynthetic pathway, causing early-onset fatal hypertrophic cardiomyopathy
source: Am. J. Hum. Genet. 72:101-14
year: 2003

http://identifiers.org/pubmed/18173545
type: PublicationXref
id: 18173545
author: Calamita, G
author: Svelto, M
author: Portincasa, P
author: Palasciano, G
db: Pubmed
title: Aquaporins in the hepatobiliary tract. Which, where and what they do in health and disease
source: Eur J Clin Invest 38:1-10
year: 2008

Telomere C-strand (Lagging Strand) Synthesis
type: Pathway
data source: Provenance1
pathway component: REACT 233106.1
pathway component: REACT 235491.1
evidence: Evidence226
xref: RelationshipXref117
xref: UnificationXref1953
xref: UnificationXref1952
pathway order: PathwayStep222
pathway order: PathwayStep218
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref3940
type: UnificationXref
id: 379744
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379744

UnificationXref3941
type: UnificationXref
id: REACT_15607
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15607.1

UnificationXref3945
type: UnificationXref
id: REACT_215130
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_215130.2

UnificationXref3944
type: UnificationXref
id: 5613628
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613628

UnificationXref3943
type: UnificationXref
id: 5613626
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613626

UnificationXref3942
type: UnificationXref
id: P48525
db: UniProt

UnificationXref3949
type: UnificationXref
id: 113522
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113522

UnificationXref3948
type: UnificationXref
id: REACT_15900
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15900.1

UnificationXref3947
type: UnificationXref
id: 379740
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379740

UnificationXref3946
type: UnificationXref
id: CHEBI:29168
db: ChEBI

UnificationXref3950
type: UnificationXref
id: REACT_4410
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4410.2

UnificationXref3951
type: UnificationXref
id: CHEBI:29166
db: ChEBI

UnificationXref3952
type: UnificationXref
id: 379753
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379753

UnificationXref3954
type: UnificationXref
id: P13188
db: UniProt

UnificationXref3953
type: UnificationXref
id: REACT_15807
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15807.1

UnificationXref3956
type: UnificationXref
id: 5613687
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613687

UnificationXref3955
type: UnificationXref
id: 5613685
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613685

UnificationXref3958
type: UnificationXref
id: 159549
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159549

UnificationXref3957
type: UnificationXref
id: REACT_207043
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_207043.2

UnificationXref3959
type: UnificationXref
id: REACT_7329
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_7329.2

SHC1 events in ERBB4 signaling
type: Pathway
data source: Provenance1
pathway component: REACT 245154.1
evidence: Evidence439
xref: UnificationXref3021
xref: UnificationXref3022
pathway order: PathwayStep237
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

CCNB:p-T14-CDK1 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry453
component stoichiometry: Stoichiometry452
component: PhysicalEntity38
component: Protein610
xref: UnificationXref1692
cellular location: GO_0005829
comment: Reactome DB_ID: 5611803

UnificationXref3927
type: UnificationXref
id: 379698
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379698

CCNB:CDK1 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry451
component stoichiometry: Stoichiometry450
component: PhysicalEntity38
component: Protein609
xref: UnificationXref1690
cellular location: GO_0005829
comment: Reactome DB_ID: 5611802

UnificationXref3926
type: UnificationXref
id: CHEBI:29158
db: ChEBI

RNA primer-DNA primer:origin duplex with DNA damage (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry457
component stoichiometry: Stoichiometry456
component: PhysicalEntity30
component: PhysicalEntity40
xref: UnificationXref1739
cellular location: GO_0005654
comment: Reactome DB_ID: 5611219

UnificationXref3925
type: UnificationXref
id: REACT_5003
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5003.2

MAD2*CDC20 complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry455
component stoichiometry: Stoichiometry454
component: Protein613
component: Protein612
xref: UnificationXref1709
cellular location: GO_0005829
comment: Reactome DB_ID: 5611310

UnificationXref3924
type: UnificationXref
id: 113553
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113553

cytoplasmic Cyclin B1:Cdc2 complexes
type: Complex
data source: Provenance1
member physical entity: Cyclin B1:phospho-Cdc2 ( Thr 14) (name copied from entity in Homo sapiens)
member physical entity: Cyclin B1:phospho-Cdc2(Thr 161, Thr 14, Tyr 15) (name copied from entity in Homo sapiens)
member physical entity: phospho-cyclin B1(CRS):phosph-Cdc2(Thr 161) (name copied from entity in Homo sapiens)
xref: UnificationXref1775
cellular location: GO_0005829
comment: Reactome DB_ID: 5611777
comment: Converted from EntitySet in Reactome

UnificationXref3923
type: UnificationXref
id: REACT_15813
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15813.1

Cyclin B:Cdk1 complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry459
component stoichiometry: Stoichiometry458
component: Protein509
component: Protein614
xref: UnificationXref1744
cellular location: GO_0005654
comment: Reactome DB_ID: 5611247

UnificationXref3922
type: UnificationXref
id: 379715
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379715

http://identifiers.org/pubmed/8723348
type: PublicationXref
id: 8723348
author: Jefferson, AB
author: Pot, DA
author: Deuter-Reinhard, M
author: Masiarz, FR
author: Cousens, LS
author: Williams, LT
author: Chin, SM
author: Norris, FA
author: Kavanaugh, WM
author: Majerus, PW
db: Pubmed
title: Multiple forms of an inositol polyphosphate 5-phosphatase form signaling complexes with Shc and Grb2
source: Curr Biol 6:438-45
year: 1996

UnificationXref3921
type: UnificationXref
id: CHEBI:29186
db: ChEBI

Cyclin B1:phospho-Cdc2 ( Thr 14) (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry460
component stoichiometry: Stoichiometry461
component: Protein610
component: Protein539
xref: UnificationXref1764
cellular location: GO_0005829
comment: Reactome DB_ID: 5611741

UnificationXref3920
type: UnificationXref
id: REACT_220347
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_220347.2

RNA primer-DNA primer:origin duplex:PCNA (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry444
component stoichiometry: Stoichiometry445
component: Complex88
component: Complex98
xref: UnificationXref1608
cellular location: GO_0005654
comment: Reactome DB_ID: 5608178

phospho-Cdc25C:14-3-3 protein complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry449
component stoichiometry: Stoichiometry448
component: PhysicalEntity7
component: Protein608
xref: UnificationXref1681
cellular location: GO_0005829
comment: Reactome DB_ID: 5610390

UnificationXref3929
type: UnificationXref
id: P15179
db: UniProt

Ub-p-S123-CDC25A (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry446
component stoichiometry: Stoichiometry447
component: PhysicalEntity6
component: Protein601
xref: UnificationXref1651
cellular location: GO_0005829
comment: Reactome DB_ID: 5608195

UnificationXref3928
type: UnificationXref
id: REACT_16074
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_16074.1

http://identifiers.org/pubmed/1894595
type: PublicationXref
id: 1894595
author: Burbaum, JJ
author: Schimmel, P
db: Pubmed
title: Structural relationships and the classification of aminoacyl-tRNA synthetases
source: J Biol Chem 266:16965-8
year: 1991

UnificationXref3930
type: UnificationXref
id: 5613655
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613655

UnificationXref3936
type: UnificationXref
id: REACT_15650
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15650.1

UnificationXref3935
type: UnificationXref
id: 379754
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379754

UnificationXref3938
type: UnificationXref
id: REACT_4423
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4423.2

UnificationXref3937
type: UnificationXref
id: 113552
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113552

UnificationXref3932
type: UnificationXref
id: 5613658
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613658

UnificationXref3931
type: UnificationXref
id: 5613656
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613656

UnificationXref3934
type: UnificationXref
id: CHEBI:29175
db: ChEBI

UnificationXref3933
type: UnificationXref
id: REACT_212234
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_212234.2

UnificationXref3939
type: UnificationXref
id: CHEBI:29157
db: ChEBI

UnificationXref1684
type: UnificationXref
id: 5618102
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618102

UnificationXref1683
type: UnificationXref
id: REACT_221999
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_221999.2

UnificationXref1686
type: UnificationXref
id: 5618019
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618019

http://identifiers.org/pubmed/11851405
type: PublicationXref
id: 11851405
author: Lin, Zheng
author: Liu, Alice Y-C
author: Manalo, Dominador J
db: Pubmed
title: Redox-dependent regulation of the conformation and function of human heat shock factor 1
source: Biochemistry 41:2580-8
year: 2002

UnificationXref1685
type: UnificationXref
id: REACT_220678
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_220678.2

http://identifiers.org/pubmed/21173190
type: PublicationXref
id: 21173190
author: Agarwal, AK
author: Prasad, SS
author: Garg, A
db: Pubmed
title: Enzymatic activities of the human AGPAT isoform 3 and isoform 5: localization of AGPAT5 to mitochondria
source: J Lipid Res 52:451-62
year: 2011

UnificationXref1680
type: UnificationXref
id: 5610389
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610389

UnificationXref1682
type: UnificationXref
id: 5610391
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610391

UnificationXref1681
type: UnificationXref
id: 5610390
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610390

UnificationXref3908
type: UnificationXref
id: 5613643
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613643

UnificationXref3909
type: UnificationXref
id: 5613645
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613645

UnificationXref3906
type: UnificationXref
id: P38714
db: UniProt

UnificationXref3907
type: UnificationXref
id: 5613642
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613642

UnificationXref3900
type: UnificationXref
id: REACT_17365
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_17365.1

UnificationXref3901
type: UnificationXref
id: CHEBI:18366
db: ChEBI

UnificationXref1687
type: UnificationXref
id: REACT_212267
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_212267.2

UnificationXref3904
type: UnificationXref
id: Q05506
db: UniProt

UnificationXref1688
type: UnificationXref
id: 5611801
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611801

UnificationXref3905
type: UnificationXref
id: 5613638
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613638

UnificationXref1689
type: UnificationXref
id: 5611800
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611800

UnificationXref3902
type: UnificationXref
id: 379708
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379708

UnificationXref3903
type: UnificationXref
id: REACT_16098
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_16098.1

UnificationXref1697
type: UnificationXref
id: 5618311
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618311

UnificationXref1696
type: UnificationXref
id: REACT_191666
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_191666.3

UnificationXref1695
type: UnificationXref
id: 5611806
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611806

UnificationXref1694
type: UnificationXref
id: 5611804
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611804

UnificationXref1693
type: UnificationXref
id: P32944
db: UniProt

UnificationXref1692
type: UnificationXref
id: 5611803
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611803

UnificationXref1691
type: UnificationXref
id: 5611733
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611733

UnificationXref1690
type: UnificationXref
id: 5611802
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611802

NOD1/2 Signaling Pathway
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction159
evidence: Evidence321
xref: UnificationXref2477
xref: UnificationXref2478
xref: RelationshipXref165
pathway order: PathwayStep314
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref3917
type: UnificationXref
id: P25345
db: UniProt

UnificationXref3918
type: UnificationXref
id: 5613649
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613649

UnificationXref3919
type: UnificationXref
id: 5613651
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613651

http://identifiers.org/pubmed/16483939
type: PublicationXref
id: 16483939
author: Pacek, M
author: Kubota, Y
author: Takisawa, H
author: Tutter, AV
author: Walter, JC
db: Pubmed
title: Localization of MCM2-7, Cdc45, and GINS to the site of DNA unwinding during eukaryotic DNA replication
source: Mol Cell 21:581-7
year: 2006

http://identifiers.org/pubmed/8411712
type: PublicationXref
id: 8411712
author: Kamijo, K
author: Osumi, T
author: Hashimoto, T
db: Pubmed
title: PMP70, the 70-kDa peroxisomal membrane protein: a member of the ATP-binding cassette transporters
source: Nippon Rinsho 51:2343-52
year: 1993

UnificationXref3910
type: UnificationXref
id: REACT_204380
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_204380.2

UnificationXref3911
type: UnificationXref
id: 379703
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379703

UnificationXref3912
type: UnificationXref
id: REACT_15752
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15752.2

UnificationXref3913
type: UnificationXref
id: 379699
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379699

UnificationXref3914
type: UnificationXref
id: REACT_15719
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15719.1

http://identifiers.org/pubmed/9110970
type: PublicationXref
id: 9110970
author: Lingner, J
author: Shevchenko, A
author: Hughes, TR
author: Lundblad, V
author: Mann, M
author: Cech, TR
db: Pubmed
title: Reverse transcriptase motifs in the catalytic subunit of telomerase
source: Science 276:561-7
year: 1997

UnificationXref1698
type: UnificationXref
id: REACT_188488
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_188488.3

UnificationXref3915
type: UnificationXref
id: 379718
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379718

UnificationXref1699
type: UnificationXref
id: 5610388
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610388

UnificationXref3916
type: UnificationXref
id: REACT_16009
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_16009.1

http://identifiers.org/pubmed/3049610
type: PublicationXref
id: 3049610
author: Smith, BL
author: Agre, P
author: Denker, BM
author: Kuhajda, FP
db: Pubmed
title: Identification, purification, and partial characterization of a novel Mr 28,000 integral membrane protein from erythrocytes and renal tubules
source: J Biol Chem 263:15634-42
year: 1988

UnificationXref1660
type: UnificationXref
id: 5608216
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608216

UnificationXref1662
type: UnificationXref
id: REACT_253409
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_253409.1

UnificationXref1661
type: UnificationXref
id: 5608218
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608218

UnificationXref1664
type: UnificationXref
id: REACT_224831
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_224831.2

UnificationXref1663
type: UnificationXref
id: 5608202
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608202

http://identifiers.org/pubmed/16339074
type: PublicationXref
id: 16339074
author: Supakorndej, T
author: Tomlinson, RL
author: Terns, RM
author: Ziegler, TD
author: Terns, MP
db: Pubmed
title: Cell cycle-regulated trafficking of human telomerase to telomeres
source: Mol Biol Cell 17:955-65
year: 2006

ChEBI:58548 S-methyl-5-thio-D-ribulose 1-phosphate(2?)
type: SmallMoleculeReference
name: S-methyl-5-thio-D-ribulose 1-phosphate(2?)
xref: UnificationXref2645

UnificationXref1665
type: UnificationXref
id: 5618016
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618016

UnificationXref1666
type: UnificationXref
id: REACT_245870
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_245870.1

UnificationXref1667
type: UnificationXref
id: 5618012
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618012

UnificationXref1668
type: UnificationXref
id: REACT_259368
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_259368.1

UnificationXref1669
type: UnificationXref
id: 5618013
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618013

UnificationXref1671
type: UnificationXref
id: 5618014
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618014

UnificationXref1670
type: UnificationXref
id: REACT_229548
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_229548.1

Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
type: Pathway
data source: Provenance1
pathway component: Inflammasomes
pathway component: NOD1/2 Signaling Pathway
evidence: Evidence326
xref: UnificationXref2502
xref: UnificationXref2503
xref: RelationshipXref166
pathway order: PathwayStep319
pathway order: PathwayStep315
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref1675
type: UnificationXref
id: REACT_202187
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_202187.2

UnificationXref1674
type: UnificationXref
id: 5608221
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608221

http://identifiers.org/pubmed/17008356
type: PublicationXref
id: 17008356
author: Monroy, N
author: Kretz, C
author: Mandel, JL
author: Payrastre, B
author: Dondaine, N
author: Tronchère, H
author: Zanoteli, E
author: Rohde, HM
author: Tosch, V
author: Laporte, J
db: Pubmed
title: A novel PtdIns3P and PtdIns(3,5)P2 phosphatase with an inactivating variant in centronuclear myopathy
source: Hum Mol Genet 15:3098-106
year: 2006

UnificationXref1673
type: UnificationXref
id: 5608220
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608220

UnificationXref1672
type: UnificationXref
id: REACT_229583
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_229583.1

http://identifiers.org/pubmed/8325892
type: PublicationXref
id: 8325892
author: Froguel, P
author: Velho, G
author: Stoffel, M
author: Vionnet, N
author: Cohen, D
author: Takeda, J
author: St. Charles, R
author: Bell, GI
author: Vaxillaire, M
author: Pilkis, SJ
author: Weber, IT
author: Gidh-Jain, M
author: Shimada, F
author: Nishi, S
author: Harrison, RW
author: Makino, H
author: Xu, LZ
db: Pubmed
title: Structure/function studies of human beta-cell glucokinase. Enzymatic properties of a sequence polymorphism, mutations associated with diabetes, and other site-directed mutants.
source: J Biol Chem 268:15200-4
year: 1993

http://identifiers.org/pubmed/22649417
type: PublicationXref
id: 22649417
author: Siddle, Kenneth
db: Pubmed
title: Molecular basis of signaling specificity of insulin and IGF receptors: neglected corners and recent advances
source: Front Endocrinol (Lausanne) 3:34
year: 2012

UnificationXref1678
type: UnificationXref
id: 5610512
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610512

UnificationXref1679
type: UnificationXref
id: REACT_224577
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_224577.2

UnificationXref1676
type: UnificationXref
id: 5610384
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610384

UnificationXref1677
type: UnificationXref
id: 5610386
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610386

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P41939
data source: Provenance1
name: Isocitrate dehydrogenase 2 (NADP), mitochondrial
name: P41939
xref: UnificationXref8995
feature: FragmentFeature1629
cellular location: GO_0005759
comment: Reactome DB_ID: 5614854
display name: IDH2

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P21954
data source: Provenance1
name: Isocitrate dehydrogenase 2 (NADP), mitochondrial
name: P21954
xref: UnificationXref8994
feature: FragmentFeature1628
cellular location: GO_0005759
comment: Reactome DB_ID: 5614853
display name: IDH2

Homologues of IDH2
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref8997
cellular location: GO_0005759
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5614856

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: UniProt:P28241
data source: Provenance1
name: Isocitrate dehydrogenase (NAD) subunit alpha, mitochondrial precursor
name: isocitrate dehydrogenase 3 (NAD+) alpha
name: NAD+-specific ICDH
name: P28241
name: Isocitric dehydrogenase
xref: UnificationXref8989
feature: FragmentFeature1627
cellular location: GO_0005759
comment: Reactome DB_ID: 5608651
display name: IDH3A

SequenceSite799
type: SequenceSite
position status: EQUAL
sequence position: 440

SequenceSite798
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite797
type: SequenceSite
position status: EQUAL
sequence position: 189

SequenceSite796
type: SequenceSite
position status: EQUAL
sequence position: 205

UnificationXref1879
type: UnificationXref
id: 5611893
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611893

SequenceSite795
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref1878
type: UnificationXref
id: REACT_230653
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_230653.1

SequenceSite794
type: SequenceSite
position status: EQUAL
sequence position: 195

SequenceSite793
type: SequenceSite
position status: EQUAL
sequence position: 440

SequenceSite792
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref1875
type: UnificationXref
id: 5611891
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611891

SequenceSite791
type: SequenceSite
position status: EQUAL
sequence position: 373

UnificationXref1874
type: UnificationXref
id: 5611890
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611890

SequenceSite790
type: SequenceSite
position status: EQUAL
sequence position: 274

UnificationXref1877
type: UnificationXref
id: 5618315
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618315

UnificationXref1876
type: UnificationXref
id: REACT_245011
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_245011.1

Evidence649
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/2207149
xref: http://identifiers.org/pubmed/10368288
xref: http://identifiers.org/pubmed/3276514
comment: The eEF1B complex binds to eEF1A and regulates its activity by catalyzing the release of GDP. Subsequently, GTP is able to bind eEF1A allowing the formation of the ternary complex (eEF1A-GTP-aa-tRNA).In metazoans eEF1 protein family is composed of four subunits: eEF1A and eEF1B alpha, beta, and gamma (formerly EF-1alpha, EF-1beta, EF-1delta, and EF-1gamma, respectively). Both eEF1B alpha and eEF1B beta function as nucleotide exchange proteins. eEF1B gamma associates with eEF1B alpha and stimulates its exchange activity. This process is illustrated below with a GTP molecule in white and eEF1A protein in yellow.The three subunits of eEF1B are also shown.

UnificationXref1870
type: UnificationXref
id: 5611889
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611889

UnificationXref692
type: UnificationXref
id: 5609480
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609480

Evidence647
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: At the beginning of this reaction, 1 molecule of 'eEF2', and 1 molecule of 'GTP' are present. At the end of this reaction, 1 molecule of 'eEF2:GTP' is present. This reaction takes place in the 'cytosol'.

UnificationXref1871
type: UnificationXref
id: REACT_234485
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_234485.1

UnificationXref691
type: UnificationXref
id: P39935
db: UniProt

Evidence648
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12297040
comment: The mechanism of a peptide bond requires the movement of three protons. First the deprotonation of the ammonium ion generates a reactive amine, allowing a nucleophilic attack on the carbonyl group. This is followed by the loss of a proton from the reaction intermediate, only to be taken up by the oxygen on the leaving group (from the end of the amino acid chain bound to the tRNA in the P-site). The peptide bond formation results in the net loss of one water molecule, leaving a deacylated-tRNA in the P-site, and a nascent polypeptide chain one amino acid larger in the A-site. For the purpose of illustration, the figures used in the section show one amino acid being added to a peptidyl-tRNA with a growing peptide chain.

UnificationXref1872
type: UnificationXref
id: P53197
db: UniProt

UnificationXref690
type: UnificationXref
id: 5609476
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609476

Evidence645
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/1620067
xref: http://identifiers.org/pubmed/12297040
comment: The A- and P-sites of the ribosome positions the aa-tRNA and peptidyl-tRNA such that a nucleophilic attack can occur between the amine group of the A-site aa-tRNA and the carbonyl group of the growing peptide chain on the P-site tRNA, resulting in the formation of a peptide bond. The carboxyl end of the peptide chain is uncoupled from the tRNA molecule in the P-site and forms a new peptide bond with the amino acid that is in the A-site. This process is illustrated below with: a peptidyl-tRNA with a growing peptide,a deacylated tRNA with an -OH and a ribosome with A,P and E sites to accommodate these three forms of tRNA.

UnificationXref1873
type: UnificationXref
id: 5611863
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611863

Evidence646
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/1620067
xref: http://identifiers.org/pubmed/1703007
comment: Following peptide bond formation, GTP-bound eEF2 catalyzes the translocation of the deacylated tRNA in the P-site and the peptidyl-tRNA in the A-site (the pre-translocation state) into the E- and P- sites (the post-translocation state), respectively. Thus, the mRNA advances by three bases to expose the next codon in the A-site. After translocation, GDP-bound eEF2 leaves the ribosome to allow another round of elongation. eEF2 is reactivated by the release of GDP and binds GTP for subsequent rounds. This process is illustrated below with a peptidyl-tRNA with a growing peptide, a deacylated tRNA with an -OH and a ribosome with A,P and E sites to accommodate these three forms of tRNA is also shown.

UnificationXref696
type: UnificationXref
id: 5609467
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609467

Evidence643
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8722040
comment: Once the correct codon-anticodon match occurs between the mRNA and aa-tRNA, the decoding event triggers GTP hydrolysis on eEF1A. The resulting conformational change releases the aa-tRNA to the A-site, and GDP bound form eEF1A is released from the ribosome. Insight into the mechanics of this system has been obtained from earlier works with rabbit reticulocytes and the E.coli system. This process is illustrated below with: an amino acyl-tRNA with an amino acid, a peptidyl-tRNA with a growing peptide and a ribosome with A,P and E sites to accommodate these two forms of tRNA.

UnificationXref695
type: UnificationXref
id: 5609466
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609466

Evidence644
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/6568109
comment: Once the correct codon-anticodon match occurs between the mRNA and aa-tRNA, the decoding event triggers GTP hydrolysis on eEF1A. The resulting conformational change releases the aa-tRNA to the A-site, and GDP bound form of eEF1A is released from the ribosome. This process is illustrated below with: an amino acyl-tRNA with an amino acid,a peptidyl-tRNA with a growing peptide and a ribosome with A,P and E sites to accommodate these two forms of tRNA.

UnificationXref694
type: UnificationXref
id: P10081
db: UniProt

Evidence641
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: The cycle of elongation starts with an empty ribosomal A-site and the peptidyl-tRNA in the P-site. eEF1A is activated by GTP binding and allows for the subsequent binding of aminoacyl-tRNA (aa-tRNA).This process is illustrated below with a GTP molecule in white and eEF1A protein in yellow.

UnificationXref693
type: UnificationXref
id: 5609481
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609481

Evidence642
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/2207148
comment: The binding of eEF1A:GTP to aminoacyl tRNA (aa-tRNA) results in the formation of a ternary complex (eEF1A:GTP:aa-tRNA). Human eEF1A and rabbit eEF1A are 100% identical, and prokaryotic homologue of eEF1A (EF-Tu) shows 59% identity in the GTP-binding domain.This process is illustrated below with: a GTP molecule in white and eEF1A protein in yellow.

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P08679
data source: Provenance1
name: P08679
name: Citrate synthase, mitochondrial precursor
name: citrate synthase
xref: UnificationXref8968
feature: FragmentFeature1621
cellular location: GO_0005759
comment: Reactome DB_ID: 5608670
display name: CS

http://identifiers.org/pubmed/21356517
type: PublicationXref
id: 21356517
author: Roach, PJ
author: Glushka, John
author: Contreras, Christopher J
author: Ishihara, Mayumi
author: Heiss, Christian
author: Tagliabracci, Vincent S
author: Hurley, TD
author: Karthik, Chandra
author: Azadi, Parastoo
author: DePaoli-Roach, Anna A
db: Pubmed
title: Phosphate incorporation during glycogen synthesis and Lafora disease
source: Cell Metab. 13:274-82
year: 2011

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: ProteinReference946
data source: Provenance1
name: P00890
name: Citrate synthase, mitochondrial precursor
name: citrate synthase
xref: UnificationXref8970
feature: FragmentFeature1622
cellular location: GO_0005759
comment: Reactome DB_ID: 5608674
display name: CS

UnificationXref699
type: UnificationXref
id: P38912
db: UniProt

Evidence640
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: The process for translation of a protein destined for the endoplasmic reticulum (ER) branches from the canonical cytoslic translation process at the point when a nascent polypeptide containing a hydrophobic signal sequence is exposed on the surface of the cytosolic ribosome:mRNA:peptide complex. The signal sequence mediates the interaction of this complex with a cytosolic signal recognition particle (SRP) to form a complex which in turn docks with an SRP receptor complex on the ER membrane. There the ribosome complex is transferred from the SRP complex to a translocon complex embedded in the ER membrane and reoriented so that the nascent polypeptide protrudes through a pore in the translocon into the ER lumen. Translation, which had been halted by SRP binding, now resumes, the signal peptide is cleaved from the polypeptide, and elongation proceeds, with the growing polypeptide oriented into the ER lumen.

UnificationXref698
type: UnificationXref
id: 5609482
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609482

UnificationXref697
type: UnificationXref
id: 5609468
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609468

isocitrate dehydrogenase 3 (NAD+) gamma
type: Protein
entity reference: ProteinReference949
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Isocitrate dehydrogenase (NAD) subunit gamma, mitochondrial precursor
name: NAD+-specific ICDH
name: P28834
name: Isocitric dehydrogenase
xref: UnificationXref8986
feature: FragmentFeature1625
cellular location: GO_0005759
comment: Reactome DB_ID: 5608656
display name: IDH3G

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: ProteinReference949
data source: Provenance1
name: NAD+-specific ICDH
name: Isocitrate dehydrogenase (NAD) subunit beta, mitochondrial precursor
name: isocitrate dehydrogenase 3 (NAD+) beta
name: P28834
name: Isocitric dehydrogenase
xref: UnificationXref8987
feature: FragmentFeature1626
cellular location: GO_0005759
comment: Reactome DB_ID: 5608655
display name: IDH3B

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P43635
data source: Provenance1
name: P43635
name: Citrate synthase, mitochondrial precursor
name: citrate synthase
xref: UnificationXref8972
feature: FragmentFeature1623
cellular location: GO_0005759
comment: Reactome DB_ID: 5608678
display name: CS

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: ProteinReference948
data source: Provenance1
name: aconitase 2, mitochondrial
name: Aconitase
name: Aconitate hydratase, mitochondrial precursor
name: Citrate hydro-lyase
name: P19414
xref: UnificationXref8980
feature: FragmentFeature1624
cellular location: GO_0005759
comment: Reactome DB_ID: 5608664
display name: ACO2

Glycine cleavage system L protein
type: Protein
entity reference: Q02733
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Dihydrolipoamide dehydrogenase, mitochondrial
name: Q02733
xref: UnificationXref8943
feature: FragmentFeature1618
cellular location: GO_0005759
comment: Reactome DB_ID: 5608764
display name: DLD

Glycine cleavage system L protein
type: Protein
entity reference: P09624
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Dihydrolipoamide dehydrogenase, mitochondrial
name: P09624
xref: UnificationXref8941
feature: FragmentFeature1617
cellular location: GO_0005759
comment: Reactome DB_ID: 5608760
display name: DLD

SequenceSite789
type: SequenceSite
position status: EQUAL
sequence position: 216

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P53170
data source: Provenance1
name: Pyruvate dehydrogenase kinase isoform 1
name: P53170
xref: UnificationXref8957
feature: FragmentFeature1620
cellular location: GO_0005759
comment: Reactome DB_ID: 5612963
display name: PDK1

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P12695
data source: Provenance1
name: Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex
name: ODP2_HUMAN
name: PBC
name: pyruvate dehydrogenase E2 subunit
name: PDC-E2
name: 2xLipo-DLAT
name: P12695
name: M2 antigen complex 70 kDa subunit
name: Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial precursor
name: 70 kDa mitochondrial autoantigen of primary biliary cirrhosis
xref: UnificationXref8949
feature: ModificationFeature318
feature: FragmentFeature1619
feature: ModificationFeature317
cellular location: GO_0005759
comment: Reactome DB_ID: 5608890
display name: E2

SequenceSite786
type: SequenceSite
position status: EQUAL
sequence position: 491

Homologues of CS
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref8973
cellular location: GO_0005759
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5608679

SequenceSite785
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite788
type: SequenceSite
position status: EQUAL
sequence position: 603

SequenceSite787
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite782
type: SequenceSite
position status: EQUAL
sequence position: 1032

http://identifiers.org/pubmed/1939222
type: PublicationXref
id: 1939222
author: Cox, TM
author: Gardner, LC
author: Smith, SJ
db: Pubmed
title: Biosynthesis of delta-aminolevulinic acid and the regulation of heme formation by immature erythroid cells in man
source: J Biol Chem 266:22010-8
year: 1991

UnificationXref1869
type: UnificationXref
id: 5611887
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611887

SequenceSite781
type: SequenceSite
position status: EQUAL
sequence position: 1

http://identifiers.org/pubmed/12655297
type: PublicationXref
id: 12655297
author: Janicke, RU
author: Schulze-Osthoff, K
author: Fischer, U
db: Pubmed
title: Many cuts to ruin: a comprehensive update of caspase substrates
source: Cell Death Differ 10:76-100
year: 2003

UnificationXref1868
type: UnificationXref
id: 5611886
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611886

SequenceSite784
type: SequenceSite
position status: EQUAL
sequence position: 231

http://identifiers.org/pubmed/1939224
type: PublicationXref
id: 1939224
author: Manning, DR
author: Lounsbury, KM
author: Brass, LF
author: Casey, PJ
db: Pubmed
title: Phosphorylation of Gz in human platelets. Selectivity and site of modification
source: J Biol Chem 266:22051-6
year: 1991

UnificationXref1867
type: UnificationXref
id: 5611885
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611885

SequenceSite783
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref1866
type: UnificationXref
id: 5611876
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611876

UnificationXref1865
type: UnificationXref
id: P52286
db: UniProt

UnificationXref1864
type: UnificationXref
id: 5611884
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611884

SequenceSite780
type: SequenceSite
position status: EQUAL
sequence position: 330

UnificationXref1863
type: UnificationXref
id: P39014
db: UniProt

UnificationXref1861
type: UnificationXref
id: Q12018
db: UniProt

Evidence656
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Protein synthesis is accomplished through the process of translation of an mRNA sequence into a polypeptide chain. This process can be divided into three distinct stages: initiation, elongation and termination. During the initiation phase, the two subunits of the ribosome are brought together to the translation start site on the mRNA where the polypeptide chain is to begin. Extension of the polypeptide chain occurs when a specific aminoacyl-tRNA, as determined by the template mRNA, binds an elongating ribosome. The protein chain is released from the ribosome when any one of three stop codons in the relevant reading frame on the mRNA is reached. Individual reactions at each one of these stages are catalyzed by a number of initiation, elongation and release factors, respectively.

UnificationXref1862
type: UnificationXref
id: 5611880
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611880

Evidence657
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Gene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are processed. Most annotation is centered on the generation of messenger RNAs (mRNAs) by regulated RNA polymerase II (PolII) transcription, although the activities of PolI and PolIII are also covered briefly, as are some aspects of microRNA generation and function. Aspects of mRNA synthesis annotated here include the assembly of transcription factor complexes and their role in targeting specific genes for transcription, PolII-mediated transcription (RNA synthesis) itself, and the co- and post-translational processing of this RNA, via capping, splicing, and 3'-cleavage and polyadenylation to yield mature mRNA molecules that are exported from the nucleus. mRNA editing and nonsense-mediated decay are also annotated. Processes leading to mRNA breakdown are described: deadenylation-dependent mRNA decay, microRNA-mediated RNA cleavage, and regulation of mRNA stability by proteins that bind AU-rich elements. Other pathways included here are tRNA aminoacylation and snRNP assembly.

UnificationXref681
type: UnificationXref
id: 5611349
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611349

Evidence658
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/6120771
comment: Many biosynthetic reactions are coupled to the cleavage of ATP to yield AMP and pyrophosphate. These reactions are typically freely reversible when carried out with purified substrates and enzymes in vitro. In vivo, however, the pyrophosphate is rapdily and essentially irreversibly hydrolyzed by a ubiquitous inorganic pyrophosphatase. This hydrolysis has the effect of pulling the first reaction strongly in the direction of biosynthesis, at the expense of two high-energy phosphate bonds. Studies of human cells have identified two forms of the enzyme, one localized to the cytosol and the other to the mitochondrial matrix (Raja et al. 1981).

UnificationXref1860
type: UnificationXref
id: REACT_241497
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_241497.1

UnificationXref680
type: UnificationXref
id: 5609871
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609871

Evidence659
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10209023
comment: During the synthesis of actin and tubulin, the nascent ribosome-associated chains bind to the heteromeric chaperone protein, prefoldin (PFD) (Hansen et al., 1999).

UnificationXref683
type: UnificationXref
id: REACT_254484
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_254484.1

Evidence652
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9712840
xref: http://identifiers.org/pubmed/7990965
comment: Please note that this reaction was inferred from experiments performed using Saccharomyces cerevisiae.

UnificationXref682
type: UnificationXref
id: 5611350
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611350

Evidence653
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10358005
comment: Please note that this reaction was inferred from experiments performed using Saccharomyces cerevisiae.

UnificationXref685
type: UnificationXref
id: 5611340
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611340

Evidence654
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10358005
comment: Please note that this reaction was inferred from experiments performed using Saccharomyces cerevisiae.

UnificationXref684
type: UnificationXref
id: 5611338
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611338

Evidence655
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/2684966
xref: http://identifiers.org/pubmed/15314182
comment: The arrival of any of the three stop codons (UAA, UAG and UGA) into the ribosomal A-site triggers the binding of a release factor (RF) to the ribosome and subsequent polypeptide chain release. In eukaryotes, the RF is composed of two proteins, eRF1 and eRF3. eRF1 is responsible for the hydrolysis of the peptidyl-tRNA, while eRF3 provides a GTP-dependent function. The ribosome releases the mRNA and dissociates into its two complex subunits, which can reassemble on another molecule to begin a new round of protein synthesis. It should be noted that at present, there is no factor identified in eukaryotes that would be the functional equivalent of the bacterial ribosome release (or recycling) factor, RRF, that catalyzes dissociation of the ribosome from the mRNA following release of the polypeptide

UnificationXref687
type: UnificationXref
id: P07260
db: UniProt

UnificationXref686
type: UnificationXref
id: 5611341
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611341

UnificationXref689
type: UnificationXref
id: P39936
db: UniProt

Evidence650
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: At the beginning of this reaction, 1 molecule of 'eEF1B alpha', 1 molecule of 'eEF1B gamma', and 1 molecule of 'eEF1B beta' are present. At the end of this reaction, 1 molecule of 'eEF1B complex' is present. This reaction takes place in the 'cytosol'.

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38857
data source: Provenance1
name: Mitochondrial pyruvate carrier 2
name: P38857
name: BRP44
xref: UnificationXref8925
feature: FragmentFeature1613
cellular location: GO_0005743
comment: Reactome DB_ID: 5613394
display name: MPC2

UnificationXref688
type: UnificationXref
id: 5609472
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609472

Evidence651
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: PublicationXref1526
xref: http://identifiers.org/pubmed/15189156
xref: http://identifiers.org/pubmed/9265629
comment: The translation elongation cycle adds one amino acid at a time to a growing polypeptide according to the sequence of codons found in the mRNA. The next available codon on the mRNA is exposed in the aminoacyl-tRNA (aa-tRNA) binding site (A site) on the 30S subunit. A: Ternary complexes of aa -tRNA:eEF1A:GTP enter the ribosome and enable the anticodon of the tRNA to make a codon/anticodon interaction with the A-site codon of the mRNA. B: Upon cognate recognition, the eEF1A:GTP is brought into the GTPase activating center of the ribosome, GTP is hydrolyzed and eEF1A:GDP leaves the ribosome. C: The peptidyl transferase center of ribosome catalyses the formation of a peptide bond between the incoming amino acid and the peptide found in the peptidyl-tRNA binding site (P site). D: In the pre-translocation state of the ribosome, the eEF2:GTP enters the ribosome, physically translocating the peptidyl-tRNA out of the A site to P site and leaves the ribosome eEF2:GDP. This action of eEF2:GTP accounts for the precise movement of the mRNA by 3 nucleotides.Consequently, deacylated tRNA is shifted to the E site. A ribosome associated ATPase activity is proposed to stimulate the release of deacylated tRNA from the E site subsequent to translocation (Elskaya et al., 1991). In this post-translocation state, the ribosome is now ready to receive a new ternary complex. This process is illustrated below with: an amino acyl-tRNA with an amino acid, a peptidyl-tRNA with a growing peptide, a deacylated tRNA with an -OH, and a ribosome with A,P and E sites to accommodate these three forms of tRNA.

P53157
type: Protein
entity reference: P53157
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: BRP44L
name: Mitochondrial pyruvate carrier 1
xref: UnificationXref8928
feature: FragmentFeature1614
cellular location: GO_0005743
comment: Reactome DB_ID: 5613386
display name: MPC1

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P32473
data source: Provenance1
name: Pyruvate dehydrogenase E1 component beta subunit, mitochondrial precursor
name: ODPA_HUMAN
name: PDHE1-B
name: pyruvate dehydrogenase E1 beta apoprotein
name: P32473
xref: UnificationXref8933
feature: FragmentFeature1615
cellular location: GO_0005759
comment: Reactome DB_ID: 5608883
display name: PDHB

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P16387
data source: Provenance1
name: ODPA_HUMAN
name: P16387
name: pyruvate dehydrogenase E1 alpha apoprotein
name: Pyruvate dehydrogenase E1 component alpha subunit, somatic form, mitochondrial precursor
name: PDHE1-A type I
xref: UnificationXref8935
feature: FragmentFeature1616
cellular location: GO_0005759
comment: Reactome DB_ID: 5608879
display name: PDHA1

Homologues of DLD
type: Protein
data source: Provenance1
member physical entity: Glycine cleavage system L protein
xref: UnificationXref8944
cellular location: GO_0005759
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5608765

CDC28
type: ProteinReference
name: UniProt:P00546
xref: UnificationXref1071
organism: http://identifiers.org/taxonomy/4932

Intrinsic Pathway for Apoptosis
type: Pathway
data source: Provenance1
pathway component: Release of apoptotic factors from the mitochondria
evidence: Evidence40
xref: UnificationXref314
xref: UnificationXref313
xref: RelationshipXref19
pathway order: PathwayStep38
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

RelationshipXref7
type: RelationshipXref
id: GO:0004676
db: GENE ONTOLOGY
relationship type: MI:0355

http://identifiers.org/pubmed/16311595
type: PublicationXref
id: 16311595
author: Forgetta, Vince
author: Tirone, Jamie C
author: Rosenblatt, DS
author: Watkins, D
author: Fujiwara, T Mary
author: Morel, Chantal F
author: Dunbar, Gail V
author: Dobson, C Melissa
author: Atkinson, Janet L
author: Shoubridge, EA
author: Pawelek, Peter D
author: Gravel, RA
author: Lerner-Ellis, Jordan P
author: Moras, Emily
author: Coulton, James W
author: Leclerc, Daniel
author: Doré, Carole
author: Morgan, Kenneth
author: Antonicka, Hana
author: Lepage, Pierre
author: Hosack, Angela R
author: Rommens, JM
db: Pubmed
title: Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type
source: Nat. Genet. 38:93-100
year: 2006

RelationshipXref8
type: RelationshipXref
id: 5614438
db: Reactome Database ID Release 49
relationship type: RelationshipTypeVocabulary2
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5614438

P53311
type: Protein
entity reference: P53311
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Mitochondrial pyruvate carrier 2
name: BRP44
xref: UnificationXref8923
feature: FragmentFeature1612
cellular location: GO_0005743
comment: Reactome DB_ID: 5613390
display name: MPC2

RelationshipXref9
type: RelationshipXref
id: GO:0047372
db: GENE ONTOLOGY
relationship type: MI:0355

Homologues of MPC2
type: Protein
data source: Provenance1
member physical entity: P53311
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref8926
cellular location: GO_0005743
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5613395

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P51601
data source: Provenance1
name: GTP cyclohydrolase 1
name: P51601
name: GCH1_HUMAN
xref: UnificationXref8904
feature: FragmentFeature1611
cellular location: GO_0005829
comment: Reactome DB_ID: 5616070
display name: GCH1

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P39692
data source: Provenance1
name: MyrG-NOS3
name: N-myristoylated eNOS (Gly2)
xref: UnificationXref8894
feature: FragmentFeature1610
feature: ModificationFeature200
cellular location: GO_0000139
comment: Reactome DB_ID: 5612909
display name: P39692

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: UniProt:Q12354
data source: Provenance1
name: Q12354
name: LYPLA1
xref: UnificationXref8890
feature: FragmentFeature1609
cellular location: GO_0005829
comment: Reactome DB_ID: 5612951
display name: APT1

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P39692
data source: Provenance1
name: 2xPalmC-MyrG-NOS3
name: palmitylated, N-myristoylated eNOS
xref: UnificationXref8879
feature: ModificationFeature200
feature: ModificationFeature198
feature: FragmentFeature1608
feature: ModificationFeature199
cellular location: GO_0000139
comment: Reactome DB_ID: 5612945
display name: P39692

UnificationXref1897
type: UnificationXref
id: REACT_235796
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_235796.1

UnificationXref1896
type: UnificationXref
id: 5618273
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618273

Evidence629
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9732867
xref: http://identifiers.org/pubmed/7000367
xref: http://identifiers.org/pubmed/592399
xref: http://identifiers.org/pubmed/641056
xref: PublicationXref1504
comment: The 80S ribosome bound to the mRNA moves along the mRNA molecule from its initial site to the initiation codon and forms a 48S complex, in which the initiation codon is base paired to the anticodon of the Met-tRNAi. Proper recognition of the AUG initiation codon depends on base pairing with the anticodon of the Met-tRNAi and requires eIF1, eIF1A, eIF2 and eIF5.

UnificationXref1899
type: UnificationXref
id: REACT_238910
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_238910.1

Evidence628
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9732867
xref: PublicationXref1504
comment: The AUG initiation codon in the mRNA is recognized by base pairing with the anticodon of the Met-tRNAi. This reaction requires eIF1, eIF1A, eIF2 and eIF5.

http://identifiers.org/pubmed/18240029
type: PublicationXref
id: 18240029
author: Luttrell, LM
db: Pubmed
title: Reviews in molecular biology and biotechnology: transmembrane signaling by G protein-coupled receptors
source: Mol Biotechnol 39:239-64
year: 2008

UnificationXref1898
type: UnificationXref
id: 5618274
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618274

Evidence627
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10364207
xref: http://identifiers.org/pubmed/7000367
xref: http://identifiers.org/pubmed/9045610
xref: http://identifiers.org/pubmed/592399
xref: http://identifiers.org/pubmed/641056
xref: http://identifiers.org/pubmed/8943342
comment: The mRNA-bound ribosomal complex moves along the 5'-untranslated region (5'-UTR) of the mRNA from its initial site to the initiation codon to form a 48S complex, in which the initiation codon (AUG) is base paired to the anticodon of the Met-tRNAi. It is not known whether eIF4A (or another ATPase, such as DED1) facilitates scanning by melting mRNA secondary structures or by actively propelling the ribosome.

Mitotic G2-G2/M phases
type: Pathway
data source: Provenance1
pathway component: REACT 236569.1
evidence: Evidence201
xref: UnificationXref1860
xref: UnificationXref1859
pathway order: PathwayStep197
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref674
type: UnificationXref
id: 5609812
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609812

Evidence621
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/1104615
comment: The ternary complex forms upon binding of the initiator methionyl-tRNA to the active eIF2:GTP complex.

UnificationXref673
type: UnificationXref
id: 5609811
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609811

Evidence622
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: PublicationXref1495
xref: http://identifiers.org/pubmed/592399
xref: http://identifiers.org/pubmed/641056
xref: http://identifiers.org/pubmed/429297
comment: The ternary complex (Met-tRNAi:eIF2:GTP) binds to the complex formed by the 40S subunit, eIF3 and eIF1A, to form the 43S complex. eIF1A promotes binding of the ternary complex to the 40S subunit within 43S. The initiator methionyl-tRNA from the ternary complex is positioned at the ribosomal P site.

UnificationXref1890
type: UnificationXref
id: 5611869
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611869

UnificationXref672
type: UnificationXref
id: 5609810
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609810

UnificationXref1891
type: UnificationXref
id: 5611870
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611870

UnificationXref671
type: UnificationXref
id: 5609526
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609526

Evidence620
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/1104615
comment: Activation of eIF2 through direct binding of GTP.

http://identifiers.org/pubmed/8325954
type: PublicationXref
id: 8325954
author: Ciaraldi, TP
author: Hueckstaedt, TP
author: Wilkinson, W
author: Olefsky, JM
author: Garvey, WT
author: Pilch, PF
db: Pubmed
title: Insulin-responsive human adipocytes express two glucose transporter isoforms and target them to different vesicles
source: J Clin Endocrinol Metab 77:286-9
year: 1993

UnificationXref1892
type: UnificationXref
id: 5611872
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611872

UnificationXref670
type: UnificationXref
id: P05317
db: UniProt

Evidence625
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/291969
xref: http://identifiers.org/pubmed/6853548
comment: The factor eIF4E within the eIF4F (cap-binding) complex directly binds the 5'-cap on eukaryotic mRNAs. Note that the mRNA is in complex with cytoplasmic proteins constituting an mRNP complex.

UnificationXref1893
type: UnificationXref
id: REACT_260659
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_260659.1

Evidence626
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9732867
xref: http://identifiers.org/pubmed/6853548
xref: http://identifiers.org/pubmed/592399
xref: http://identifiers.org/pubmed/641056
comment: The cap-binding complex is constituted by the initiation factors eIF4A, eIF4G and eIF4E. First, eIF4E must be released from the inactive eIF4E:4E-BP complex. Then eIF4A interacts with eIF4G, and eIF4E binds to the amino-terminal domain of eIF4G, resulting in the formation of the cap-binding complex eIF4F. eIF4A together with eIF4B or eIF4H is thought to unwind RNA secondary structures near the 5'-end of the mRNA. The translation initiation complex is formed when the 43S complex binds the cap-bound mRNA.

UnificationXref1894
type: UnificationXref
id: 5618314
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618314

Evidence623
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: PublicationXref1495
xref: http://identifiers.org/pubmed/592399
xref: http://identifiers.org/pubmed/641056
xref: http://identifiers.org/pubmed/1104615
xref: http://identifiers.org/pubmed/429297
comment: Binding of the methionyl-tRNA initiator to the active eIF2:GTP complex results in the formation of the ternary complex. Subsequently, this Met-tRNAi:eIF2:GTP (ternary) complex binds to the complex formed by the 40S subunit, eIF3 and eIF1A, to form the 43S complex.

UnificationXref1895
type: UnificationXref
id: REACT_253415
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_253415.1

Evidence624
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8449919
comment: eIF4A interacts with eIF4G, and eIF4E interacts with the amino-terminal domain of eIF4G to form the cap-binding complex eIF4F.

Metabolism of nitric oxide
type: Pathway
data source: Provenance1
pathway component: REACT 189005.3
evidence: Evidence1393
xref: UnificationXref8920
xref: RelationshipXref1044
xref: UnificationXref8921
pathway order: PathwayStep1376
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P43637
data source: Provenance1
name: P43637
name: LKB-1
xref: UnificationXref8858
feature: FragmentFeature1606
cellular location: GO_0005654
comment: Reactome DB_ID: 5611565
display name: STK11

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P39692
data source: Provenance1
name: MyrG-NOS3
name: N-myristoylated eNOS (Gly2)
xref: UnificationXref8876
feature: ModificationFeature200
feature: FragmentFeature1607
cellular location: GO_0005829
comment: Reactome DB_ID: 5612907
display name: P39692

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P06782
data source: Provenance1
name: P06782
name: AMPK alpha2
xref: UnificationXref8849
feature: FragmentFeature1604
cellular location: GO_0005654
comment: Reactome DB_ID: 5611510
display name: PRKAA2

RelationshipXref2
type: RelationshipXref
id: 5614058
db: Reactome Database ID Release 49
relationship type: RelationshipTypeVocabulary2
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5614058

phospho-p-T172-PRKAA2
type: Protein
entity reference: P06782
data source: Provenance1
xref: UnificationXref8855
feature: FragmentFeature1605
feature: ModificationFeature196
cellular location: GO_0005654
comment: Reactome DB_ID: 5611560

UnificationXref679
type: UnificationXref
id: 5609783
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609783

RelationshipXref1
type: RelationshipXref
id: GO:0004517
db: GENE ONTOLOGY
relationship type: MI:0355

UnificationXref678
type: UnificationXref
id: 5609782
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609782

RelationshipXref4
type: RelationshipXref
id: 5614064
db: Reactome Database ID Release 49
relationship type: RelationshipTypeVocabulary2
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5614064

UnificationXref677
type: UnificationXref
id: P49166
db: UniProt

RelationshipXref3
type: RelationshipXref
id: GO:0047555
db: GENE ONTOLOGY
relationship type: MI:0355

UnificationXref676
type: UnificationXref
id: 5609778
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609778

RelationshipXref6
type: RelationshipXref
id: 5614053
db: Reactome Database ID Release 49
relationship type: RelationshipTypeVocabulary2
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5614053

http://identifiers.org/pubmed/14739288
type: PublicationXref
id: 14739288
author: Dowd, LO
author: Augustin, R
author: Phay, JE
author: Moley, JF
author: Moley, KH
author: Carayannopoulos, MO
db: Pubmed
title: Identification and characterization of human glucose transporter-like protein-9 (GLUT9): alternative splicing alters trafficking
source: J Biol Chem 279:16229-36
year: 2004

UnificationXref675
type: UnificationXref
id: P51402
db: UniProt

RelationshipXref5
type: RelationshipXref
id: GO:0005388
db: GENE ONTOLOGY
relationship type: MI:0355

http://identifiers.org/pubmed/16321791
type: PublicationXref
id: 16321791
author: Joseph, JW
author: MacDonald, PE
author: Rorsman, P
db: Pubmed
title: Glucose-sensing mechanisms in pancreatic beta-cells
source: Philos Trans R Soc Lond B Biol Sci 360:2211-25
year: 2005

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P34164
data source: Provenance1
name: P34164
name: AMPK beta2
xref: UnificationXref8847
feature: FragmentFeature1602
cellular location: GO_0005654
comment: Reactome DB_ID: 5611514
display name: PRKAB2

adenine nucleotide translocator 3
type: Protein
entity reference: ProteinReference932
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Adenine nucleotide translocator 3
name: ADP/ATP translocase 3 monomer
name: P04710
name: SLC25A6
name: ADP/ATP translocase 3
name: ADP,ATP carrier protein, liver isoform T2
xref: UnificationXref8829
feature: FragmentFeature1601
cellular location: GO_0005743
comment: Reactome DB_ID: 5611496
display name: ANT 3

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P12904
data source: Provenance1
name: AMPK gamma2
name: P12904
xref: UnificationXref8848
feature: FragmentFeature1603
cellular location: GO_0005654
comment: Reactome DB_ID: 5611518
display name: PRKAG2

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P41735
data source: Provenance1
name: P41735
name: COQ7_HUMAN
name: Ubiquinone biosynthesis protein COQ7 homolog
xref: UnificationXref8804
feature: FragmentFeature1598
cellular location: GO_0005743
comment: Reactome DB_ID: 5616873
display name: COQ7

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: UniProt:P49017
data source: Provenance1
name: COQ5_HUMAN
name: P49017
name: 2-methoxy-6-polyprenyl-1,4-benzoquinol methylase, mitochondrial ecNumber2.1.1.201/ecNumber
xref: UnificationXref8795
feature: FragmentFeature1597
cellular location: GO_0005759
comment: Reactome DB_ID: 5616863
display name: COQ5

Adenine nucleotide translocator 2
type: Protein
entity reference: AAC3
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: adenine nucleotide translocator 2
name: ADP/ATP translocase 2 monomer
name: SLC25A5
name: P18238
name: ADP,ATP carrier protein, fibroblast isoform
name: ADP/ATP translocase 2
xref: UnificationXref8826
feature: FragmentFeature1600
cellular location: GO_0005743
comment: Reactome DB_ID: 5611491
display name: ANT 2

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: PET9
data source: Provenance1
name: ADP/ATP translocase 1
name: ADP,ATP carrier protein, heart/skeletal muscle isoform T1
name: SLC25A4
name: P18239
name: adenine nucleotide translocator 1
name: Adenine nucleotide translocator 1
name: ADP/ATP translocase 1 monomer
xref: UnificationXref8823
feature: FragmentFeature1599
cellular location: GO_0005743
comment: Reactome DB_ID: 5611486
display name: ANT 1

UnificationXref1888
type: UnificationXref
id: REACT_5692
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5692.2

Evidence639
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9631292
xref: http://identifiers.org/pubmed/12853463
comment: The SRP receptor in the the endoplasmic reticulum (ER) membrane binds via its alpha subunit to the the SRP54 subunit of the Signal Recognition Particle (SRP), which itself is bound to a ribosome:mRNA:polypeptide complex. This interaction tethers the ribosome to the ER membrane, oriented so that the nacent polypeptide will traverse the ER membrane and enter the ER lumen. This process has been characterized in detail in cultured canine cells; this human event is inferred by homology from its canine counterpart.

UnificationXref1887
type: UnificationXref
id: 111294
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111294

Evidence638
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/20444697
comment: The synthesis of a protein destined for the endoplasmic reticulum starts with the canonical events of cytosolic translation initiation and proceeds to the point where a nascent polypeptide chain containing a signal sequence protrudes from the mRNA:ribosome complex. Merrick (2010) provides an overview of these events.

UnificationXref1886
type: UnificationXref
id: CHEBI:29888
db: ChEBI

UnificationXref1885
type: UnificationXref
id: 5611865
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611865

UnificationXref1889
type: UnificationXref
id: Q00684
db: UniProt

UnificationXref661
type: UnificationXref
id: 5609847
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609847

Evidence630
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/1095581
xref: http://identifiers.org/pubmed/10659855
comment: Once the 60S subunit joins the translation initiation complex, eIF5B hydrolyzes its GTP and is released from the now 80S monosome. The fully assembled 80s ribosome is now ready to start elongation of the polypeptide chain.

UnificationXref1880
type: UnificationXref
id: 5611894
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611894

UnificationXref660
type: UnificationXref
id: P17076
db: UniProt

Evidence631
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/1095581
xref: http://identifiers.org/pubmed/10659855
xref: http://identifiers.org/pubmed/592398
comment: Joining of the 60S subunit to form the 80S ribosome is catalyzed by the presence of GTP-bound eIF5B.

UnificationXref663
type: UnificationXref
id: 5609851
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609851

Evidence632
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/1095581
xref: http://identifiers.org/pubmed/10659855
xref: http://identifiers.org/pubmed/592398
xref: http://identifiers.org/pubmed/11018020
xref: http://identifiers.org/pubmed/592399
xref: http://identifiers.org/pubmed/641056
xref: http://identifiers.org/pubmed/429297
xref: http://identifiers.org/pubmed/1856230
comment: Hydrolysis of eIF2-GTP occurs after the Met-tRNAi has recognized the AUG. This reaction is catalyzed by eIF5 (or eIF5B) and is thought to cause dissociation of all other initiation factors and allow joining of the large 60S ribosomal subunit. The 60S subunit joins - a reaction catalyzed by eIF5 or eIF5B - resulting in a translation-competent 80S ribosome. Following 60S subunit joining, eIF5B hydrolyzes its GTP and is released from the 80S ribosome, which is now ready to start elongating the polypeptide chain.

UnificationXref662
type: UnificationXref
id: P29453
db: UniProt

Evidence633
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/2491852
xref: http://identifiers.org/pubmed/3356695
comment: Inactive eIF2:GDP binds eIF2B to form an eIF2:GDP:eIF2B intermediate.

UnificationXref1883
type: UnificationXref
id: 5618272
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618272

Evidence634
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/2491852
xref: http://identifiers.org/pubmed/3356695
comment: eIF2B is a guanine nucleotide releasing factor that is required to cause GDP release so that a new GTP molecule can bind and activate eIF2, so that it can be reused.

UnificationXref1884
type: UnificationXref
id: REACT_188466
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_188466.3

Evidence635
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/7063012
comment: The active eIF2:GTP complex may be formed by direct binding of GTP to free eIF2 or by GDP-GTP exchange on the eIF2:GDP:eIF2B complex. The eIF2:GDP complex binds eIF2B forming an eIF2:GDP:eIF2B intermediate complex. eIF2B is a guanine nucleotide releasing factor required to cause GDP release so that a new GTP molecule can bind and activate eIF2. Phosphorylated eIF2:GDP sequesters all eIF2B as an inactive complex, and thus, reuse of eIF2 is inhibited as a consequence of the tight bond it forms with eIF2B, which prevents nucleotide exchange. Therefore, in the absence of free eIF2B, excess eIF2 remains in its inactive GDP-bound form and protein synthesis slows dramatically.

UnificationXref1881
type: UnificationXref
id: 5611896
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611896

Evidence636
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Translation initiation is a complex process in which the Met-tRNAi initiator, 40S, and 60S ribosomal subunits are assembled by eukaryotic initiation factors (eIFs) into an 80S ribosome at the start codon of an mRNA. The basic mechanism for this process can be described as a series of five steps: 1) formation of a pool of free 40S subunits, 2) formation of the ternary complex (Met-tRNAi/eIF2/GTP), and subsequently, the 43S complex (comprising the 40S subunit, Met-tRNAi/eIF2/GTP, eIF3 and eIF1A), 3) activation of the mRNA upon binding of the cap-binding complex eIF4F, and factors eIF4A, eIF4B and eIF4H, with subsequent binding to the 43S complex, 4) ribosomal scanning and start codon recognition, and 5) GTP hydrolysis and joining of the 60S ribosomal subunit.

http://identifiers.org/pubmed/14638855
type: PublicationXref
id: 14638855
author: Voos, W
author: Müller, H
author: Pfanner, N
author: Truscott, KN
author: Guiard, B
author: Meyer, HE
author: Meisinger, C
author: Sickmann, A
author: Lind, M
author: Rehling, P
author: Frazier, AE
author: Geissler, A
author: Dudek, J
author: Li, Y
db: Pubmed
title: A J-protein is an essential subunit of the presequence translocase-associated protein import motor of mitochondria
source: J Cell Biol 163:707-13
year: 2003

UnificationXref1882
type: UnificationXref
id: REACT_191689
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_191689.3

Evidence637
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/20444697
comment: Initiation of translation in the majority of eukaryotic cellular mRNAs depends on the 5'-cap (m7GpppN) and involves ribosomal scanning of the 5' untranslated region (5'-UTR) for an initiating AUG start codon. Therefore, this mechanism is often called cap-dependent translation initiation. Proximity to the cap, as well as the nucleotides surrounding an AUG codon, influence the efficiency of the start site recognition during the scanning process. However, if the recognition site is poor enough, scanning ribosomal subunits will ignore and skip potential starting AUGs, a phenomenon called leaky scanning. Leaky scanning allows a single mRNA to encode several proteins that differ in their amino-termini. Merrick (2010) provides an overview of this process and hghlights several features of it that remain incompletely understood. Several eukaryotic cell and viral mRNAs initiate translation by an alternative mechanism that involves internal initiation rather than ribosomal scanning. These mRNAs contain complex nucleotide sequences, called internal ribosomal entry sites, where ribosomes bind in a cap-independent manner and start translation at the closest downstream AUG codon. Initiation on several viral and cellular mRNAs is cap-independent and is mediated by binding of the ribosome to internal ribosome entry site (IRES) elements. These elements are often found in characteristically long structured regions on the 5'-UTR of an mRNA that may or may not have regulatory upstream open reading frames (uORFs). Both of these features on the 5'-end of the mRNA hinder ribosomal scanning, and thus promote a cap-independent translation initiation mechanism. IRESs act as specific translational enhancers that allow translation initiation to occur in response to specific stimuli and under the control of different trans-acting factors, as for example when cap-dependent protein synthesis is shut off during viral infection. Such regulatory elements have been identified in the mRNAs of growth fa…

UnificationXref669
type: UnificationXref
id: 5609834
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609834

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: Q06147
data source: Provenance1
name: Q06147
name: CERK1_HUMAN
name: Ceramide kinase
xref: UnificationXref8748
feature: FragmentFeature1594
cellular location: GO_0005886
comment: Reactome DB_ID: 5616294
display name: CERK

UnificationXref668
type: UnificationXref
id: 5609833
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609833

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P53318
data source: Provenance1
name: Ubiquinone biosynthesis monooxygenase COQ6 ecNumber1.14.13.-/ecNumber
name: P53318
name: COQ6_HUMAN
xref: UnificationXref8771
feature: FragmentFeature1595
cellular location: GO_0005743
comment: Reactome DB_ID: 5616856
display name: COQ6

COQ3_HUMAN
type: Protein
entity reference: P27680
data source: Provenance1
name: Hexaprenyldihydroxybenzoate methyltransferase, mitochondrial ecNumber2.1.1.114/ecNumber
name: Note: the coordinates are copied over from Homo sapiens.
name: P27680
name: COQ3(?-369)
xref: UnificationXref8785
feature: FragmentFeature1596
cellular location: GO_0005759
comment: Reactome DB_ID: 5616850
display name: COQ3

CDC19
type: ProteinReference
name: UniProt:P00549
xref: UnificationXref2120
organism: http://identifiers.org/taxonomy/4932

UnificationXref665
type: UnificationXref
id: P05739
db: UniProt

UnificationXref664
type: UnificationXref
id: 5609852
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609852

UnificationXref667
type: UnificationXref
id: Q02326
db: UniProt

UnificationXref666
type: UnificationXref
id: 5609829
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609829

UnificationXref1834
type: UnificationXref
id: 5618310
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618310

SequenceSite750
type: SequenceSite
position status: EQUAL
sequence position: 360

UnificationXref3977
type: UnificationXref
id: REACT_210344
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_210344.2

UnificationXref1835
type: UnificationXref
id: REACT_188487
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_188487.3

SequenceSite751
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref3978
type: UnificationXref
id: CHEBI:29174
db: ChEBI

UnificationXref1836
type: UnificationXref
id: 5611842
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611842

UnificationXref3975
type: UnificationXref
id: 5613666
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613666

http://identifiers.org/pubmed/9792106
type: PublicationXref
id: 9792106
author: Hazlett, TL
author: Sanchez, SA
author: Jameson, DM
author: Brunet, JE
db: Pubmed
title: Aggregation states of mitochondrial malate dehydrogenase
source: Protein Sci 7:2184-2189
year: 1998

UnificationXref1837
type: UnificationXref
id: 5611843
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611843

UnificationXref3976
type: UnificationXref
id: 5613668
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613668

UnificationXref1830
type: UnificationXref
id: REACT_8297
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_8297.1

UniProt:P00560
type: ProteinReference
name: PGK1
xref: UnificationXref6195
organism: http://identifiers.org/taxonomy/4932

UnificationXref1831
type: UnificationXref
id: 5611833
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611833

UnificationXref1832
type: UnificationXref
id: 5611835
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611835

UnificationXref3979
type: UnificationXref
id: 379750
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379750

UnificationXref1833
type: UnificationXref
id: REACT_191721
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_191721.3

SequenceSite758
type: SequenceSite
position status: EQUAL
sequence position: 602

SequenceSite759
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite756
type: SequenceSite
position status: EQUAL
sequence position: 601

SequenceSite757
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref1838
type: UnificationXref
id: 5611845
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611845

SequenceSite754
type: SequenceSite
position status: EQUAL
sequence position: 589

UnificationXref1839
type: UnificationXref
id: REACT_216773
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_216773.2

SequenceSite755
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite752
type: SequenceSite
position status: EQUAL
sequence position: 816

http://identifiers.org/pubmed/12573255
type: PublicationXref
id: 12573255
author: Hegele, RA
author: Cao, H
author: Mok, A
db: Pubmed
title: Genomic basis of mucopolysaccharidosis type IIID (MIM 252940) revealed by sequencing of GNS encoding N-acetylglucosamine-6-sulfatase
source: Genomics 81:1-5
year: 2003

SequenceSite753
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref655
type: UnificationXref
id: P51401
db: UniProt

Evidence684
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Glycosylphosphatidyl inositol (GPI) acts as a membrane anchor for many cell surface proteins. GPI is synthesized in the endoplasmic reticulum. In humans, a single pathway consisting of eleven reactions appears to be responsible for the synthesis of the major GPI species involved in membrane protein anchoring. As a nascent protein fated to become GPI-anchored moves into the lumen of the endoplasmic reticulum, it is attacked by a transamidase complex that cleaves it near its carboxy terminus and attaches an acylated GPI moiety. The GPI moiety is deacylated, yielding a protein-GPI conjugate that can be efficiently transported to the Golgi apparatus.

UnificationXref656
type: UnificationXref
id: 5609865
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609865

Evidence683
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15632136
xref: http://identifiers.org/pubmed/15208306
xref: http://identifiers.org/pubmed/11102867
comment: Glycosylphosphatidyl inositol (GPI) acts as a membrane anchor for many cell surface proteins. GPI is synthesized in the endoplasmic reticulum. In humans, a single pathway consisting of nine reactions appears to be responsible for the synthesis of the major GPI species involved in membrane protein anchoring. This pathway is shown in the figure. Two additional reactions, not shown, allow the synthesis of variant forms of GPI, one with an additional mannose residue and one with an additional ethanolamine (Tauron et al. 2004; Shishioh et al. 2005). These variant GPI molecules may be used for tissue-specific protein modifications, or may function independently. The steps of GPI synthesis were first identified by isolating large numbers of mutant cell lines that had lost the ability to express GPI anchored proteins on their surfaces. Somatic cell hybrid analyses of these lines allowed the definition of complementation groups corresponding to distinct mutated genes, and cDNAs corresponding to normal forms of these genes were identified on the basis of their abilities to restore normal cell surface protein expression in mutant cells. Co-precipitation experiments with tagged cloned proteins have allowed the identification of additional proteins involved in GPI anchor biosynthesis.

UnificationXref653
type: UnificationXref
id: 5609569
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609569

Evidence682
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15632136
comment: Most human GPI anchors have ethanolamine phosphate groups attached to their first and third mannose residues, but GPI anchors with ethanolamine phosphates attached to all three mannose residues have also been identified. Addition of the third ethanolamine phosphate can be catalyzed by a complex of PIG-F and a newly described human protein, GPI7. The donor of the ethanolamine phosphate for this reaction is unknown (Shishioh et al. 2005).

UnificationXref654
type: UnificationXref
id: 5609570
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609570

Evidence681
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10781593
xref: http://identifiers.org/pubmed/8463218
comment: The final step in the main pathway for the synthesis of GPI moieties in human cells is the addition of an ethanolamine phosphate to the third mannose residue of the glycolipid, donated by phosphatidylethanolamine. This reaction has been experimentally characterized in the mouse, where studies with mutated cell lines defective in GPI biosynthesis have established the role of two proteins, PIG-F and PIG-O, in this reaction (Hong et al. 2000). While a human PIG-F protein has been identified and shown to be involved in this event (Inoue et al. 1993), the human event has not been fully characterized and is therefore annotated here as inferred from studies of the mouse event.

http://identifiers.org/pubmed/15476407
type: PublicationXref
id: 15476407
author: Tsai, AL
author: Gao, D
author: Yeh, HC
author: Kiran, F
author: Berka, V
db: Pubmed
title: Redox function of tetrahydrobiopterin and effect of L-arginine on oxygen binding in endothelial nitric oxide synthase
source: Biochemistry 43:13137-48
year: 2004

UnificationXref659
type: UnificationXref
id: 5609870
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609870

Evidence680
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8861954
comment: In the eighth reaction of GPI synthesis, a third mannose residue is added, catalyzed by PIG-B (Takahashi et al. 1996).

http://identifiers.org/pubmed/8246982
type: PublicationXref
id: 8246982
author: Wagner, BJ
author: Brewer, G
author: DeHaven, K
author: Schaefer, AW
author: Long, L
author: Crater, D
author: Ehrenman, K
author: Zhang, W
author: DeMaria, CT
db: Pubmed
title: Purification, characterization, and cDNA cloning of an AU-rich element RNA-binding protein, AUF1
source: Mol Cell Biol 13:7652-65
year: 1993

UnificationXref657
type: UnificationXref
id: P05738
db: UniProt

UnificationXref658
type: UnificationXref
id: 5609869
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609869

SequenceSite749
type: SequenceSite
position status: EQUAL
sequence position: 2

RMTs methylate histone arginines
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction250
evidence: Evidence533
xref: UnificationXref3600
xref: UnificationXref3601
pathway order: PathwayStep523
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref3970
type: UnificationXref
id: 379695
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379695

Evidence689
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/21384228
comment: Dolichol is a polyisoprenol lipid comprised of five-carbon isoprene units linked linearly in a head-to-tail fashion. Almost all eukaryotic membranes contain dolichol and its phosphorylated form is used in the N-glycosylation of proteins where it is used as an anchor for the N-glycan sugar to the ER membrane, and as an initiation point for the synthesis. Dolichol biosynthesis occurs on the cytoplasmic face of the ER membrane, which is where N-glycosylation occurs too, so is perfectly placed to serve as a substrate for this process. Dolichyl phosphate can be obtained either from direct phosphorylation of dolichol, formed in a series of reactions from mevalonate 5-pyrophosphate, or a salvage reaction by de-phosphorylation of dolichyl diphosphate, released at the end of N-glycan biosynthesis (Cantagrel & Lefeber 2011).

UnificationXref651
type: UnificationXref
id: 5609565
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609565

UnificationXref3974
type: UnificationXref
id: REACT_15671
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15671.1

Evidence688
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/6243292
comment: In the last step of the N-glycan precursor biosynthesis pathway, the mature N-glycan (Glc3Man9GlcNAc2) is removed from the dolichyl diphosphate (DOLDP) molecule upon which it has been synthesized and attached to a nascent protein. The released DOLDP molecule is de-phosphorylated by dolichyl diphosphatase 1 (DOLPP1) to dolichyl phosphate (DOLP). DOLP is thus salvaged and be used as substrate for the synthesis of another N-glycan oligosaccharide (Wedgwood & Strominger 1980).

http://identifiers.org/pubmed/15215243
type: PublicationXref
id: 15215243
author: Graf, SA
author: Shirihai, OS
author: Corson, ED
author: Haigh, SE
db: Pubmed
title: Targeting, import, and dimerization of a mammalian mitochondrial ATP binding cassette (ABC) transporter, ABCB10 (ABC-me)
source: J Biol Chem 279:42954-63
year: 2004

UnificationXref652
type: UnificationXref
id: P0C0W9
db: UniProt

UnificationXref3973
type: UnificationXref
id: 379764
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379764

Evidence687
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12213788
xref: http://identifiers.org/pubmed/17273964
comment: Dolichol kinase (DOLK, TMEM15) mediates the phosphorylation of dolichol (DCHOL) to form dolichyl phosphate (DOLP) in the ER membrane (Fernandez et al. 2002). Defects in DOLK cause congenital disorder of glycosylation type 1M (CDG1M aka dolichol kinase deficiency; MIM:610768), a severe mutisystem disorder characterised by under-glycosylated serum glycoproteins which results in nervous system under-development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. Death occurs in early life (Kranz et al. 2007).

UnificationXref3972
type: UnificationXref
id: REACT_17378
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_17378.1

Evidence686
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/14652022
xref: http://identifiers.org/pubmed/21295283
xref: http://identifiers.org/pubmed/7374371
comment: The ER membrane-associated enzyme dehydrodolichyl diphosphate synthase (DHDDS) mediates the sequential head-to-tail cis addition of multiple isopentyl pyrophosphate (IPP) molecules to farnesyl pyrophosphate (E,E-FPP) to produce polyprenol pyrophosphate (pPPP) (Shridas et al. 2003). Dolichol in humans contain homologues ranging from 17-23 isoprene units, the most common homologues contain 19 or 20 isoprene units (Freeman et al. 1980). Defects in DHDDS cause retinitis pigmentosa 59 (RP59; MIM:613861), a pigment retinopathy, characterised by retinal pigment deposits (visible on fundus examination) and primary loss of rod photoreceptors followed by secondary loss of cone photoreceptors. Sufferers typically have night vision blindness and loss of mid to peripheral vision. As the condition progresses, they lose far peripheral vision and eventually central vision (Zuchner et al. 2011).

UnificationXref650
type: UnificationXref
id: P36519
db: UniProt

UnificationXref3971
type: UnificationXref
id: 379752
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379752

Evidence685
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8626466
comment: Mevalonate pyrophosphate decarboxylase (MPD) decarboxylates mevalonate-5-pyrophosphate (MVA5PP) into isopentenyl pyrophosphate (IPPP) while hydrolysing ATP to ADP and orthophosphate (Toth & Huwyler 1996).

UnificationXref1825
type: UnificationXref
id: 5611832
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611832

UnificationXref3964
type: UnificationXref
id: 5613676
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613676

UnificationXref1826
type: UnificationXref
id: REACT_205025
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_205025.2

UnificationXref3965
type: UnificationXref
id: 5613677
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613677

UnificationXref1823
type: UnificationXref
id: 5611330
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611330

UnificationXref3966
type: UnificationXref
id: 5613678
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613678

UnificationXref1824
type: UnificationXref
id: 5611830
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611830

SequenceSite740
type: SequenceSite
position status: EQUAL
sequence position: 220

UnificationXref3967
type: UnificationXref
id: 5613679
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613679

UnificationXref1821
type: UnificationXref
id: 5611839
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611839

UnificationXref3968
type: UnificationXref
id: 5613681
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613681

UnificationXref1822
type: UnificationXref
id: REACT_213983
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_213983.2

UnificationXref3969
type: UnificationXref
id: REACT_209470
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_209470.2

CDC8
type: ProteinReference
name: UniProt:P00572
xref: UnificationXref9495
organism: http://identifiers.org/taxonomy/4932

UnificationXref1820
type: UnificationXref
id: 5611838
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611838

SequenceSite745
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite746
type: SequenceSite
position status: EQUAL
sequence position: 379

SequenceSite747
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite748
type: SequenceSite
position status: EQUAL
sequence position: 360

UnificationXref1829
type: UnificationXref
id: 182620
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=182620

SequenceSite741
type: SequenceSite
position status: EQUAL
sequence position: 2

http://identifiers.org/pubmed/8428933
type: PublicationXref
id: 8428933
author: Doroshow, JH
author: Esworthy, RS
author: Chu, FF
db: Pubmed
title: Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI
source: J Biol Chem 268:2571-6
year: 1993

SequenceSite742
type: SequenceSite
position status: EQUAL
sequence position: 816

UnificationXref1827
type: UnificationXref
id: 170150
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=170150

SequenceSite743
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref1828
type: UnificationXref
id: REACT_6526
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_6526.1

SequenceSite744
type: SequenceSite
position status: EQUAL
sequence position: 379

UniProt:P07807
type: ProteinReference
name: DFR1
xref: UnificationXref1723
organism: http://identifiers.org/taxonomy/4932

UnificationXref642
type: UnificationXref
id: 5609664
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609664

Evidence693
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11707391
comment: Cytosolic UAP1 catalyzes the reaction of N-acetyl-D-glucosamine 1-phosphate (GlcNAc1P) and UTP to UDP-N-acetyl-D-glucosamine and pyrophosphate. Structural studies indicate that the active form of the enzyme is a dimer (Peneff C et al, 2001).

UniProt:P07806
type: ProteinReference
name: VAS1
xref: UnificationXref3866
organism: http://identifiers.org/taxonomy/4932

UnificationXref643
type: UnificationXref
id: Q12672
db: UniProt

Evidence692
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12174217
comment: Cytosolic PGM3 catalyzes the isomerization of N-acetyl-D-glucosamine 6-phosphate (GlcNAc6P) to form N-acetyl-D-glucosamine 1-phosphate (GlcNAc1P) (Pang H et al, 2002).

UnificationXref644
type: UnificationXref
id: 5609655
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609655

Evidence695
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8307007
xref: http://identifiers.org/pubmed/10980531
comment: Mannose-6-phosphate isomerase (MPI) isomerizes fructose 6-phosphate (Fru6P) to mannose 6-phosphate (Man6P) (Proudfoot et al. 1994). Defects in this gene are associated with congenital disorder of glycosylation type 1B (CDG1B). Oral administration of mannose is an efficient therapy against this defect (Schollen et al. 2000).

UnificationXref645
type: UnificationXref
id: Q02753
db: UniProt

Evidence694
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: UDP-acetylglucosamine acts as a donor for the first two steps of the N-glycan precursor biosynthesis pathway, and is later used as a substrate for further modifications after the precursor has been attached to the protein. It is synthesized from fructose 6-phosphate, glutamine, acetyl-CoA, and UTP in four steps.

UnificationXref646
type: UnificationXref
id: 5609659
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609659

SequenceSite739
type: SequenceSite
position status: EQUAL
sequence position: 218

UnificationXref647
type: UnificationXref
id: 5609660
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609660

SequenceSite738
type: SequenceSite
position status: EQUAL
sequence position: 473

UnificationXref648
type: UnificationXref
id: Q3E757
db: UniProt

Evidence691
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18675810
comment: Cytosolic GNPNAT1 catalyzes the reaction of glucosamine 6-phosphate and acetyl-CoA to form N-acetyl-glucosamine 6-phosphate (GlcNAc6P) and CoA-SH. Structural studies indicate that the active form of the enzyme is a dimer (Wang J et al, 2008).

UnificationXref649
type: UnificationXref
id: 5609561
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609561

Evidence690
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/1460020
xref: http://identifiers.org/pubmed/10198162
xref: http://identifiers.org/pubmed/21310273
comment: Glucosamine-fructose 6-phosphate aminotransferases 1 and 2 (GFPT1,2) are the first and rate-limiting enzymes in the hexosamine synthesis pathway, and thus formation of hexosamines like N-acetylglucosamine (GlcNAc). These enzymes probably plays a role in limiting the availability of substrates for the N- and O- linked glycosylation of proteins (McKnight et al. 1992, Oki et al. 1999). GFPT1 and 2 are required for normal functioning of neuromuscular synaptic transmission. Defects in GFPT1 leads to altered muscle fibre morphology and impaired neuromuscular junction development (Senderek et al. 2011).

UnificationXref3961
type: UnificationXref
id: REACT_16111
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_16111.1

Evidence697
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/5946626
xref: http://identifiers.org/pubmed/11082198
comment: Mannose 1-phosphate is converted to GDP-Mannose by mannose-1-phosphate guanyltransferase alpha and beta forms (GMPPA/B). This enzyme had originally been characterized from rat and bovine sources (Verachtert H et al, 1966) and more recently from pig (Ning B and Elbein AD, 2000).

UnificationXref3960
type: UnificationXref
id: 379770
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379770

Evidence696
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9119384
xref: http://identifiers.org/pubmed/9140401
xref: http://identifiers.org/pubmed/9070917
comment: Phosphomannomutases 1 and 2 (PMM1 and PMM2) catalyze the isomerization of mannose 6-phosphate (Man6P) to mannose 1-phosphate (Man1P) in the cytosol of cells (Wada & Sakamoto 1997, Matthijs et al. 1997). Mutations in the PMM2 gene are one of the causes of Jaeken syndrome. a disease of glycosylation, type CDGIa. (Matthijs et al. 1997b).

http://identifiers.org/pubmed/6323448
type: PublicationXref
id: 6323448
author: Cline, A
author: Moulton, AD
author: Nienhuis, AW
author: Chen, MJ
author: Humphries, RK
author: Shimada, T
author: Maizel, J
db: Pubmed
title: The functional human dihydrofolate reductase gene
source: J Biol Chem 259:3933-43
year: 1984

UnificationXref640
type: UnificationXref
id: 5609606
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609606

UnificationXref3963
type: UnificationXref
id: REACT_15734
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15734.1

Evidence699
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10359825
comment: Dolichyl-phosphate beta-glucosyltransferase (ALG5) associated with the endoplasmic reticulum (ER) membrane catalyzes the reaction of cytosolic UDP-glucose with dolichyl phosphate exposed on the cytosolic face of the ER membrane to form Dolichyl-P-glucose with its glucose moiety oriented toward the cytosol (Imbach T et al, 1999).

UnificationXref641
type: UnificationXref
id: P05749
db: UniProt

UnificationXref3962
type: UnificationXref
id: 379781
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379781

Evidence698
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: GDP-mannose is the mannose donor for the first 5 mannose addition reactions in the N-glycan precursor synthesis, and also for the synthesis of Dolichyl-phosphate-mannose involved in other mannose transfer reactions. It is synthesized from fructose 6-phosphate and GTP in three steps.

UnificationXref1852
type: UnificationXref
id: 5611411
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611411

UnificationXref1853
type: UnificationXref
id: 5611412
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611412

UnificationXref1854
type: UnificationXref
id: REACT_248716
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_248716.1

UnificationXref1855
type: UnificationXref
id: 5618276
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618276

UnificationXref1856
type: UnificationXref
id: REACT_259128
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_259128.1

SequenceSite772
type: SequenceSite
position status: EQUAL
sequence position: 690

UnificationXref3999
type: UnificationXref
id: 5613611
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613611

UnificationXref1857
type: UnificationXref
id: 5618277
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618277

SequenceSite773
type: SequenceSite
position status: EQUAL
sequence position: 1

ChEBI:60125 N-epsilon-(1-(1-carboxy)ethyl)lysine
type: SmallMoleculeReference
name: N-epsilon-(1-(1-carboxy)ethyl)lysine
xref: UnificationXref2515

UnificationXref1858
type: UnificationXref
id: REACT_236569
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_236569.1

SequenceSite770
type: SequenceSite
position status: EQUAL
sequence position: 328

UnificationXref3997
type: UnificationXref
id: REACT_18097
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_18097.1

UnificationXref1859
type: UnificationXref
id: 5618278
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618278

SequenceSite771
type: SequenceSite
position status: EQUAL
sequence position: 27

UnificationXref3998
type: UnificationXref
id: P11325
db: UniProt

SequenceSite776
type: SequenceSite
position status: EQUAL
sequence position: 778

SequenceSite777
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite774
type: SequenceSite
position status: EQUAL
sequence position: 1097

SequenceSite775
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite778
type: SequenceSite
position status: EQUAL
sequence position: 1522

UnificationXref639
type: UnificationXref
id: 5609605
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609605

SequenceSite779
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref637
type: UnificationXref
id: 5609601
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609601

UnificationXref638
type: UnificationXref
id: P38754
db: UniProt

UnificationXref635
type: UnificationXref
id: 5609642
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609642

UnificationXref636
type: UnificationXref
id: P36105
db: UniProt

UnificationXref633
type: UnificationXref
id: P0CX24
db: UniProt

Evidence662
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9153422
xref: http://identifiers.org/pubmed/7909354
comment: The interaction between CCT and unfolded target proteins is thought to occur when CCT is in its ADP-bound state. ADP is then exchanged for ATP in CCT.

UnificationXref634
type: UnificationXref
id: 5609641
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609641

Evidence661
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11580269
comment: Unfolded actins and tubulins bound to prefoldin are transferred to CCT via a docking mechanism (McCormack and Willison, 2001).

UnificationXref631
type: UnificationXref
id: P0CX23
db: UniProt

Evidence660
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8104191
comment: Unfolded actins and tubulins compete efficiently for binding to TriC/CCT and their chaperonin binding sites appear to be at least in part overlapping (Melki et al., 1993).

UnificationXref632
type: UnificationXref
id: 5609639
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609639

UnificationXref3996
type: UnificationXref
id: 379773
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379773

Evidence666
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9630229
xref: http://identifiers.org/pubmed/1351421
xref: http://identifiers.org/pubmed/8104191
comment: Nucleotide-independent transfer of beta-actin from prefoldin to CCT occurs when prefoldin binds to CCT (Vainberg et al., 1998). Following ATP- dependent folding within CCT (Gao et al., 1992), beta-actin is released as a soluble, monomeric protein.

UnificationXref630
type: UnificationXref
id: 5609720
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609720

UnificationXref3995
type: UnificationXref
id: CHEBI:16624
db: ChEBI

Evidence665
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9153422
xref: http://identifiers.org/pubmed/7909354
comment: The interaction between CCT and unfolded target proteins is thought to occur when CCT is in its ADP-bound state. ADP is then exchanged for ATP in CCT.

UnificationXref3994
type: UnificationXref
id: REACT_4213
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4213.2

Evidence664
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8096061
xref: http://identifiers.org/pubmed/1361170
xref: http://identifiers.org/pubmed/11868281
xref: http://identifiers.org/pubmed/9265649
comment: TriC/CCT forms a binary complex with unfolded alpha- or beta-tubulin (Frydman et al., 1992; Gao et al., 1993). The tubulin folding intermediates produced by TriC are unstable (Gao et al., 1993). Five additional protein cofactors (cofactor A-E) are required for the generation of properly folded alpha- and beta-tubulin and for the formation of alpha/beta-tubulin heterodimers (Gao et al., 1993) (Tian et al., 1997, Cowan and Lewis 2001).

UnificationXref3993
type: UnificationXref
id: 113580
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113580

Evidence663
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12732144
comment: Group II chaperonins enclose substrate proteins following substrate binding through the formation of a "built- in" lid over the central cavity. Upon ATP binding, lid formation is triggered by the transition state of ATP hydrolysis (Meyer, et al., 2003). In the case of CCT-mediated tubulin folding, one or more rounds of ATP hydrolysis are likely required before the association of non-exchangeable GTP with chaperonin-bound alpha tubulin.

UnificationXref3992
type: UnificationXref
id: REACT_17073
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_17073.1

UnificationXref3991
type: UnificationXref
id: 379788
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379788

Evidence669
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19011634
comment: TRiC has broad recognition specificities, but in the cell it interacts with only a defined set of substrates (Yam et al. 2008). Many of its substrates that are targeted during biosynthesis are conserved between mammals and yeast (Yam et al. 2008).

UnificationXref1851
type: UnificationXref
id: 5611409
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611409

UnificationXref3990
type: UnificationXref
id: CHEBI:29169
db: ChEBI

Evidence668
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18775504
comment: CCT/TRiC facilitates folding of newly translated SK1 into its mature active form (Zebol et al., 2008)

UnificationXref1850
type: UnificationXref
id: REACT_217065
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_217065.2

Evidence667
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9630229
comment: In the case of actin and tubulin folding, and perhaps other substrates, the emerging polypeptide chain is transferred from the ribosome to TRiC via Prefoldin (Vainberg et al., 1998).

UnificationXref1843
type: UnificationXref
id: 5617324
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617324

UnificationXref1844
type: UnificationXref
id: 5617325
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617325

UnificationXref1841
type: UnificationXref
id: REACT_205363
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_205363.2

UnificationXref1842
type: UnificationXref
id: 5617323
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617323

UnificationXref1847
type: UnificationXref
id: REACT_188776
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_188776.3

UnificationXref3986
type: UnificationXref
id: P48526
db: UniProt

UnificationXref1848
type: UnificationXref
id: 5611334
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611334

SequenceSite760
type: SequenceSite
position status: EQUAL
sequence position: 309

UnificationXref3987
type: UnificationXref
id: 5613593
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613593

UnificationXref1845
type: UnificationXref
id: REACT_187982
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_187982.3

SequenceSite761
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref3988
type: UnificationXref
id: 5613595
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613595

UnificationXref1846
type: UnificationXref
id: 5618670
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618670

SequenceSite762
type: SequenceSite
position status: EQUAL
sequence position: 309

UnificationXref3989
type: UnificationXref
id: REACT_206500
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_206500.2

SequenceSite763
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite764
type: SequenceSite
position status: EQUAL
sequence position: 623

UnificationXref1849
type: UnificationXref
id: 5611336
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611336

SequenceSite765
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite766
type: SequenceSite
position status: EQUAL
sequence position: 348

UnificationXref629
type: UnificationXref
id: 5609690
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609690

SequenceSite767
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref628
type: UnificationXref
id: 5609689
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609689

SequenceSite768
type: SequenceSite
position status: EQUAL
sequence position: 293

SequenceSite769
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref624
type: UnificationXref
id: 5609721
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609721

UnificationXref625
type: UnificationXref
id: P04449
db: UniProt

UnificationXref626
type: UnificationXref
id: 5609685
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609685

http://identifiers.org/pubmed/22946059
type: PublicationXref
id: 22946059
author: Kunzelmann, Karl
author: Schreiber, Rainer
author: Tian, Yuemin
db: Pubmed
title: Anoctamins are a family of Ca2+ activated Cl- channels
source: J. Cell. Sci.
year: 2012

UnificationXref627
type: UnificationXref
id: P24000
db: UniProt

http://identifiers.org/pubmed/19129477
type: PublicationXref
id: 19129477
author: Akerfelt, Malin
author: Sistonen, Lea
author: Jolly, Caroline
author: Nymalm, Yvonne
author: Vourc'h, Claire
author: Chitikova, Zhanna
author: Salminen, Tiina A
author: Björk, Johanna K
author: Grichine, Alexei
author: Sandqvist, Anton
db: Pubmed
title: Heterotrimerization of heat-shock factors 1 and 2 provides a transcriptional switch in response to distinct stimuli
source: Mol. Biol. Cell 20:1340-7
year: 2009

UnificationXref620
type: UnificationXref
id: P40525
db: UniProt

Evidence671
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18395510
xref: http://identifiers.org/pubmed/15459659
xref: http://identifiers.org/pubmed/15519848
comment: Due to the crowded envirnoment within the cell, many proteins must interact with molecular chaperones to attain their native conformation (reviewed in Young et al., 2004). Chaperones recognize and associate with proteins in their non-native state and facilitate their folding by stabilizing the conformation of productive folding intermediates. Chaperones that take part broadly in de novo protein folding, such as the Hsp70s and the chaperonins, facilitate the folding process through cycles of substrate binding and release regulated by their ATPase activity (see Young et al., 2004; Spiess et al., 2004; Bigotti and Clarke, 2008).

UnificationXref621
type: UnificationXref
id: 5609746
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609746

Evidence670
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9630229
xref: http://identifiers.org/pubmed/12354605
xref: http://identifiers.org/pubmed/11868281
xref: http://identifiers.org/pubmed/18708324
xref: http://identifiers.org/pubmed/10753735
xref: http://identifiers.org/pubmed/11580265
xref: http://identifiers.org/pubmed/15519848
xref: http://identifiers.org/pubmed/12697815
comment: The eukaryotic chaperonin TCP-1 ring complex (TRiC/ CCT) plays an essential role in the folding of a subset of proteins prominent among which are the actins and tubulins (reviewed in Altschuler and Willison, 2008). CCT/TRiC is an example of a type II chaperonin, defined (in contrast to type I) as functioning in the absence of a cochaperonin. TriC/CCT is a multisubunit toroidal complex that forms a cylinder containing two back-to-back stacked rings enclosing a cavity where substrate folding occurs in an ATP dependent process (reviewed in Altschuler and Willison, 2008 ). CCT/TriC contains eight paralogous subunits that are conserved throughout eukaryotic organisms (Leroux and Hartl 2000; Archibald et al. 2001; Valpuesta et al. 2002). CCT-mediated folding of non-native substrate protein involves capture through hydrophobic contacts with multiple chaperonin subunits followed by transfer of the protein into the central ring cavity where it folds. Although folding is initiated within this central cavity, only 5%-20% of proteins that are released have partitioned to the native state. The remaining portion is then recaptured by other chaperonin molecules (Cowan and Lewis 2001). This cycling process may be repeated multiple times before a target protein partitions to the native state. In the cell, binding to CCT occurs via presentation of target protein bound to upstream chaperones. During translation, the emerging polypeptide chain may be transferred from the ribosome to CCT via the chaperone Prefoldin (Vainberg et al., 1998) or the Hsp70 chaperone machinery (Melville et al., 2003). While the majority of CCT substrates ultimately partition to the native state as soluble, monomeric proteins, alpha and beta tubulin are unusual in that they require additional cofactors that are required to assemble the tubulin heterodimer (Cowan and Lewis 2001).

UnificationXref622
type: UnificationXref
id: 5609747
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609747

Evidence673
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16452303
comment: The reaction of EIF5A, spermidine, and NAD+ to form EIF5A(Dhp), 1,3-diaminopropane, and NADH + H+ is reversible in vitro. Under physiological conditions, the reverse reaction is probably minimized by the rapid, irreversible conversion of FIF5A(Dhp) to EIF5A(Hyp).

UnificationXref623
type: UnificationXref
id: P14126
db: UniProt

Evidence672
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16452303
xref: http://identifiers.org/pubmed/9188485
xref: http://identifiers.org/pubmed/7673224
xref: http://identifiers.org/pubmed/14622290
comment: Cytosolic deoxyhypusine synthase catalyzes the reaction of EIF5A protein, spermidine, and NAD+ to convert lysine-50 of EIF5A to deoxyhypusine, generating 1,3-diaminopropane and NADH + H+ in the process (Park 2006). Although the reaction is reversible, the reverse reaction is probably minimized under physiological conditions by the rapid, irreversible conversion of EIF5A(Dhp) to EIF5A(Hyp).

UnificationXref3983
type: UnificationXref
id: CHEBI:29160
db: ChEBI

Evidence675
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16452303
comment: Cytosolic eIF5A undergoes a unique two-step post-translational modification at Lys 50 via deoxyhypusine (Dhp) to hypusine (Hyp). In the first step deoxyhypusine synthase transfers the aminobutyl group of spermidine to the epsilon-amino group of lysine 50, using NAD+ as a cofactor. Hydroxylation of the C2 of the newly added moiety in the second step is catalyzed by deoxyhypusine hydroxylase/monooxygenase with molecular oxygen as the source. The molecular function of eIF5A is unknown, but the protein is required for viability in eukaryotic cells and its normal function requires hypusinylation. eIF5A is the only protein known to undergo hypusinylation (Park 2006).

UnificationXref3982
type: UnificationXref
id: REACT_4106
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4106.2

Evidence674
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17213197
xref: http://identifiers.org/pubmed/16533814
xref: http://identifiers.org/pubmed/14622290
comment: Cytosolic deoxyhypusine hydroxylase catalyzes the irreversible conversion of peptidyl-deoxyhypusine to peptidyl-hypusine. The only known substrate for this enzyme is the modified lysine at residue 50 of eIF5A (Kang et al. 2007; Kim et al. 2006).

UnificationXref3985
type: UnificationXref
id: REACT_16053
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_16053.1

Evidence677
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/14742432
xref: http://identifiers.org/pubmed/10089216
comment: In the second step of GPI synthesis, N-acetylglucosaminyl-PI is hydrolyzed to yield glucosaminyl-PI and acetate. The phosphatidylinositol (PI) derivatives involved in this reaction are located in the endoplasmic reticulum membrane, as is the PIG-L enzyme that catalyzes it (Sharma et al. 1999; Pottekat and Menon 2004).

UnificationXref3984
type: UnificationXref
id: 379769
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379769

Evidence676
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: After translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the body. These modifications include the vitamin K-dependent attachment of carboxyl groups to glutamate residues and the conversion of lysine residues to hypusine.

UnificationXref1840
type: UnificationXref
id: 5618312
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618312

Evidence679
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11159918
xref: http://identifiers.org/pubmed/10574991
xref: http://identifiers.org/pubmed/10069808
comment: In the sixth step of GPI synthesis, a phosphoethanolamine group is transferred from phosphatidylethanolamine onto the first mannose of the GPI precursor. The human protein that catalyzes this reaction was first identified because it could complement a yeast mutant strain defective for GPI synthesis (Gaynor et al. 1999); its specific function in phosphoethanolamine transfer is inferred from functional studies of the homologous mouse protein (Hong et al. 1999). The reaction is annotated here with phosphatidylethanolamine as the donor of the phosphoethanolamine group on the basis of studies in yeast (Imhof et al. 2000).

Evidence678
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/14517336
comment: In the fourth step of GPI synthesis, an acyl group (typically palmitate) is transferred from acyl CoA to glucosaminyl-PI. Mutagenesis and cloning studies suggest that a single protein, PIG-W, catalyzes this reaction (Murakami et al. 2003).

UnificationXref3981
type: UnificationXref
id: 113537
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113537

UnificationXref3980
type: UnificationXref
id: REACT_15750
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15750.1

http://identifiers.org/pubmed/17560368
type: PublicationXref
id: 17560368
author: Peters, L
author: Meister, G
db: Pubmed
title: Argonaute proteins: mediators of RNA silencing
source: Mol Cell 26:611-23
year: 2007

UnificationXref610
type: UnificationXref
id: P05740
db: UniProt

SequenceSite709
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref612
type: UnificationXref
id: 5609624
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609624

UnificationXref611
type: UnificationXref
id: 5609623
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609623

UnificationXref614
type: UnificationXref
id: 5609539
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609539

SequenceSite705
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref613
type: UnificationXref
id: P05319
db: UniProt

SequenceSite706
type: SequenceSite
position status: EQUAL
sequence position: 360

UnificationXref616
type: UnificationXref
id: 5609543
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609543

SequenceSite707
type: SequenceSite
position status: EQUAL
sequence position: 185

UnificationXref615
type: UnificationXref
id: P02400
db: UniProt

SequenceSite708
type: SequenceSite
position status: EQUAL
sequence position: 187

UnificationXref617
type: UnificationXref
id: 5609544
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609544

SequenceSite713
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref618
type: UnificationXref
id: P87262
db: UniProt

SequenceSite712
type: SequenceSite
position status: EQUAL
sequence position: 187

UnificationXref619
type: UnificationXref
id: 5609742
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609742

SequenceSite715
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite714
type: SequenceSite
position status: EQUAL
sequence position: 360

SequenceSite711
type: SequenceSite
position status: EQUAL
sequence position: 185

SequenceSite710
type: SequenceSite
position status: EQUAL
sequence position: 360

http://identifiers.org/pubmed/6311078
type: PublicationXref
id: 6311078
author: Hammarström, Sven
db: Pubmed
title: Leukotrienes
source: Annu Rev Biochem 52:355-77
year: 1983

http://identifiers.org/pubmed/17785525
type: PublicationXref
id: 17785525
author: Boyault, Cyril
author: Garrido, Carmen
author: Gilquin, Benoit
author: Kwon, So Hee
author: Caron, Cécile
author: Fritah, Sabrina
author: Khochbin, Saadi
author: Vourc'h, Claire
author: Yao, Tso-Pang
author: Matthias, Patrick
author: Zhang, Yu
db: Pubmed
title: HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates
source: Genes Dev. 21:2172-81
year: 2007

http://identifiers.org/pubmed/8892014
type: PublicationXref
id: 8892014
author: Treacy, E
author: Thompson, GN
author: Pitt, JJ
author: Cotton, RG
author: Seller, K
author: Ramus, S
db: Pubmed
title: In vivo disposal of phenylalanine in phenylketonuria: a study of two siblings
source: J Inherit Metab Dis 19:595-602
year: 1996

UnificationXref601
type: UnificationXref
id: P05744
db: UniProt

UnificationXref600
type: UnificationXref
id: 5609588
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609588

UnificationXref605
type: UnificationXref
id: 5609765
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609765

UnificationXref604
type: UnificationXref
id: 5609764
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609764

UnificationXref603
type: UnificationXref
id: P41056
db: UniProt

UnificationXref602
type: UnificationXref
id: 5609760
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609760

UnificationXref608
type: UnificationXref
id: P46990
db: UniProt

SequenceSite704
type: SequenceSite
position status: EQUAL
sequence position: 360

UnificationXref609
type: UnificationXref
id: 5609619
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609619

SequenceSite703
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref606
type: UnificationXref
id: P41805
db: UniProt

SequenceSite702
type: SequenceSite
position status: EQUAL
sequence position: 400

UnificationXref607
type: UnificationXref
id: 5609548
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609548

SequenceSite701
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite700
type: SequenceSite
position status: EQUAL
sequence position: 379

Homologues of APRT
type: Protein
data source: Provenance1
member physical entity: Adenine phosphoribosyltransferase
xref: UnificationXref9326
cellular location: GO_0005829
comment: Reactome DB_ID: 5610252
comment: Converted from EntitySet in Reactome

Adenine phosphoribosyltransferase
type: Protein
entity reference: P36973
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: P36973
xref: UnificationXref9323
feature: FragmentFeature1670
cellular location: GO_0005829
comment: Reactome DB_ID: 5610247
display name: APRT

Adenine phosphoribosyltransferase
type: Protein
entity reference: P49435
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: P49435
xref: UnificationXref9325
feature: FragmentFeature1671
cellular location: GO_0005829
comment: Reactome DB_ID: 5610251
display name: APRT

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: Q07729
data source: Provenance1
name: GAH
name: Guanase
name: Guanine deaminase
name: Q07729
name: p51-nedasin
name: Guanine aminohydrolase
name: Guanine aminase
xref: UnificationXref9340
feature: FragmentFeature1672
cellular location: GO_0005829
comment: Reactome DB_ID: 5610283
display name: GDA

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P06785
data source: Provenance1
name: TYMS
name: TSase
name: P06785
name: Thymidylate synthase
xref: UnificationXref9403
feature: FragmentFeature1677
cellular location: GO_0005829
comment: Reactome DB_ID: 5609956
display name: TS

SequenceSite727
type: SequenceSite
position status: EQUAL
sequence position: 408

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: Q06549
data source: Provenance1
name: Q06549
name: Cytidine deaminase
name: Cytidine aminohydrolase
xref: UnificationXref9424
feature: FragmentFeature1678
cellular location: GO_0005829
comment: Reactome DB_ID: 5609964
display name: CDA

SequenceSite728
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite729
type: SequenceSite
position status: EQUAL
sequence position: 507

http://identifiers.org/pubmed/11572773
type: PublicationXref
id: 11572773
author: Blackburn, EH
db: Pubmed
title: Switching and signaling at the telomere
source: Cell 106:661-73
year: 2001

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P07259
data source: Provenance1
name: Aspartate carbamoyltransferase
name: P07259
name: Dihydroorotase
name: carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase
name: CAD protein (Includes: Glutamine-dependent carbamoyl-phosphate synthase (EC 6.3.5.5); Aspartate carbamoyltransferase (EC 2.1.3.2); Dihydroorotase (EC 3.5.2.3))
name: Glutamine-dependent carbamoyl-phosphate synthase
xref: UnificationXref9352
feature: FragmentFeature1673
cellular location: GO_0005829
comment: Reactome DB_ID: 5609910
display name: CAD

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P03962
data source: Provenance1
name: Orotate phosphoribosyltransferase
name: P03962
name: OMPdecase
name: OPRtase
name: UMP synthase
name: uridine monophosphate synthetase (orotate phosphoribosyl transferase and orotidine-5'-decarboxylase)
name: Uridine 5'-monophosphate synthase
name: Uridine 5'-monophosphate synthase (UMP synthase) (Includes: Orotate phosphoribosyltransferase (EC 2.4.2.10) (OPRtase); Orotidine 5'- phosphate decarboxylase (EC 4.1.1.23) (OMPdecase))
name: Orotidine 5'- phosphate decarboxylase
xref: UnificationXref9373
feature: FragmentFeature1674
cellular location: GO_0005829
comment: Reactome DB_ID: 5609901
display name: UMPS

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P06773
data source: Provenance1
name: Deoxycytidylate deaminase
name: P06773
name: dCMP deaminase
xref: UnificationXref9386
feature: FragmentFeature1675
cellular location: GO_0005829
comment: Reactome DB_ID: 5609945
display name: DCTD

P33317
type: Protein
entity reference: P33317
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: deoxyuridine triphosphatase isoform 2
name: dUTP pyrophosphatase
xref: UnificationXref9396
feature: FragmentFeature1676
cellular location: GO_0005654
comment: Reactome DB_ID: 5610000
display name: DUT-2

UnificationXref1819
type: UnificationXref
id: REACT_191659
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_191659.3

SequenceSite731
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref1818
type: UnificationXref
id: 5611826
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611826

SequenceSite730
type: SequenceSite
position status: EQUAL
sequence position: 408

UnificationXref1817
type: UnificationXref
id: REACT_191660
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_191660.3

SequenceSite733
type: SequenceSite
position status: EQUAL
sequence position: 396

UnificationXref1816
type: UnificationXref
id: 5611825
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611825

SequenceSite732
type: SequenceSite
position status: EQUAL
sequence position: 507

SequenceSite735
type: SequenceSite
position status: EQUAL
sequence position: 473

SequenceSite734
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite737
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite736
type: SequenceSite
position status: EQUAL
sequence position: 396

UnificationXref1811
type: UnificationXref
id: 5611836
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611836

UnificationXref1810
type: UnificationXref
id: REACT_208983
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_208983.2

UnificationXref1815
type: UnificationXref
id: 5611823
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611823

UnificationXref1814
type: UnificationXref
id: REACT_222568
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_222568.2

UnificationXref1813
type: UnificationXref
id: 5611841
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611841

UnificationXref1812
type: UnificationXref
id: 5611837
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611837

Homologues of AMPD2
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref9271
cellular location: GO_0005829
comment: Reactome DB_ID: 5610634
comment: Converted from EntitySet in Reactome

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P40361
data source: Provenance1
name: AMP deaminase isoform L
name: P40361
name: AMP deaminase 2 (EC 3.5.4.6) (AMP deaminase isoform L)
name: AMP deaminase 2
xref: UnificationXref9269
feature: FragmentFeature1663
cellular location: GO_0005829
comment: Reactome DB_ID: 5610632
display name: AMPD2

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38150
data source: Provenance1
name: AMP deaminase 1 (EC 3.5.4.6) (Myoadenylate deaminase) (AMP deaminase isoform M)
name: Myoadenylate deaminase
name: AMP deaminase isoform M
name: myoadenylate deaminase
name: AMP deaminase 1
name: P38150
xref: UnificationXref9266
feature: FragmentFeature1662
cellular location: GO_0005829
comment: Reactome DB_ID: 5610629
display name: AMPD1

Q05788
type: Protein
entity reference: Q05788
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: nucleoside phosphorylase
name: Purine nucleoside phosphorylase (EC 2.4.2.1) (Inosine phosphorylase) (PNP)
name: Inosine phosphorylase
name: PNP
xref: UnificationXref9310
feature: FragmentFeature1669
cellular location: GO_0005829
comment: Reactome DB_ID: 5610272
display name: NP

SequenceSite718
type: SequenceSite
position status: EQUAL
sequence position: 360

SequenceSite719
type: SequenceSite
position status: EQUAL
sequence position: 1

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P15274
data source: Provenance1
name: AMP deaminase 3
name: Erythrocyte AMP deaminase
name: AMP deaminase 3 (EC 3.5.4.6) (AMP deaminase isoform E) (Erythrocyte AMP deaminase)
name: P15274
name: AMP deaminase isoform E
name: erythrocyte AMP deaminase
xref: UnificationXref9276
feature: FragmentFeature1667
cellular location: GO_0005829
comment: Reactome DB_ID: 5610641
display name: AMPD3

SequenceSite716
type: SequenceSite
position status: EQUAL
sequence position: 360

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P53909
data source: Provenance1
name: Adenosine deaminase-like protein
name: P53909
xref: UnificationXref9288
feature: FragmentFeature1668
cellular location: GO_0005829
comment: Reactome DB_ID: 5616813
display name: ADAL

SequenceSite717
type: SequenceSite
position status: EQUAL
sequence position: 2

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P40361
data source: Provenance1
name: P40361
name: AMP deaminase 3
name: Erythrocyte AMP deaminase
name: AMP deaminase 3 (EC 3.5.4.6) (AMP deaminase isoform E) (Erythrocyte AMP deaminase)
name: AMP deaminase isoform E
name: erythrocyte AMP deaminase
xref: UnificationXref9273
feature: FragmentFeature1665
cellular location: GO_0005829
comment: Reactome DB_ID: 5610636
display name: AMPD3

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38150
data source: Provenance1
name: AMP deaminase 3
name: Erythrocyte AMP deaminase
name: AMP deaminase 3 (EC 3.5.4.6) (AMP deaminase isoform E) (Erythrocyte AMP deaminase)
name: AMP deaminase isoform E
name: P38150
name: erythrocyte AMP deaminase
xref: UnificationXref9274
feature: FragmentFeature1666
cellular location: GO_0005829
comment: Reactome DB_ID: 5610637
display name: AMPD3

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38150
data source: Provenance1
name: AMP deaminase isoform L
name: AMP deaminase 2 (EC 3.5.4.6) (AMP deaminase isoform L)
name: AMP deaminase 2
name: P38150
xref: UnificationXref9270
feature: FragmentFeature1664
cellular location: GO_0005829
comment: Reactome DB_ID: 5610633
display name: AMPD2

Homologues of AMPD3
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref9277
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5610642

UnificationXref1806
type: UnificationXref
id: 5611813
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611813

SequenceSite722
type: SequenceSite
position status: EQUAL
sequence position: 507

UnificationXref1805
type: UnificationXref
id: P30822
db: UniProt

SequenceSite721
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref1808
type: UnificationXref
id: 5611819
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611819

SequenceSite720
type: SequenceSite
position status: EQUAL
sequence position: 507

UnificationXref1807
type: UnificationXref
id: 5611818
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611818

SequenceSite726
type: SequenceSite
position status: EQUAL
sequence position: 473

UnificationXref1809
type: UnificationXref
id: 5611820
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611820

SequenceSite725
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite724
type: SequenceSite
position status: EQUAL
sequence position: 473

SequenceSite723
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref1800
type: UnificationXref
id: 5611817
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611817

'NF-Y (name copied from entity in Homo sapiens) [nucleoplasm]' positively regulates 'Expression of BIP (78 kDa Glucose-regulated protein, GRP78, HSPA5)'
type: TemplateReactionRegulation
data source: Provenance1
xref: UnificationXref5231
controlled: TemplateReaction12
control type: ACTIVATION
controller: Complex424

UnificationXref1802
type: UnificationXref
id: 5611814
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611814

http://identifiers.org/pubmed/20110263
type: PublicationXref
id: 20110263
author: Kersten, S
author: de Groot, PJ
author: de Vries, SC
author: Muller, M
author: Degenhardt, T
author: Carlberg, C
author: Vaisanen, S
author: Heinaniemi, M
author: van der Meer, DL
db: Pubmed
title: Profiling of promoter occupancy by PPAR{alpha} in human hepatoma cells via ChIP-chip analysis
source: Nucleic Acids Res
year: 2010

UnificationXref1801
type: UnificationXref
id: REACT_259379
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_259379.1

http://identifiers.org/pubmed/15276183
type: PublicationXref
id: 15276183
author: Gangloff, M
author: Gay, NJ
db: Pubmed
title: MD-2: the Toll 'gatekeeper' in endotoxin signalling
source: Trends Biochem Sci 29:294-300
year: 2004

UnificationXref1804
type: UnificationXref
id: 5611815
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611815

UnificationXref1803
type: UnificationXref
id: REACT_191661
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_191661.3

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38625
data source: Provenance1
name: guanine monophosphate synthetase
name: Glutamine amidotransferase
name: GMP synthetase
name: P38625
name: GMP synthase (glutamine-hydrolyzing)
xref: UnificationXref9212
feature: FragmentFeature1656
cellular location: GO_0005829
comment: Reactome DB_ID: 5610015
display name: GMPS

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38697
data source: Provenance1
name: IMP (inosine monophosphate) dehydrogenase 1
name: Inosine-5'-monophosphate dehydrogenase 1 (EC 1.1.1.205) (IMP dehydrogenase 1) (IMPDH-I) (IMPD 1)
name: IMP dehydrogenase 1
name: IMPDH-I
name: P38697
name: Inosine-5'-monophosphate dehydrogenase 1
name: IMPD 1
xref: UnificationXref9205
feature: FragmentFeature1655
cellular location: GO_0005829
comment: Reactome DB_ID: 5610037
display name: IMPDH1

IMP--aspartate ligase 2
type: Protein
entity reference: P80210
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Adenylosuccinate synthetase (EC 6.3.4.4) (IMP--aspartate ligase) (AdSS) (AMPSase)
name: AMPSase 2
name: Adenylosuccinate synthetase 2
name: adenylosuccinate synthetase
name: AdSS 2
name: P80210
xref: UnificationXref9222
feature: FragmentFeature1658
cellular location: GO_0005829
comment: Reactome DB_ID: 5611041
display name: ADSS

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P80210
data source: Provenance1
name: IMP--aspartate ligase 1
name: AMPSase 1
name: Adenylosuccinate synthetase isozyme 1
name: AdSS 1
name: adenylosuccinate synthetase 1
name: P80210
name: adenylosuccinate synthetase like 1
xref: UnificationXref9219
feature: FragmentFeature1657
cellular location: GO_0005829
comment: Reactome DB_ID: 5611038
display name: ADSSL1

P47143
type: Protein
entity reference: P47143
data source: Provenance1
name: Adenosine kinase
name: Note: the coordinates are copied over from Homo sapiens.
name: ADK
name: Adenosine 5'-phosphotransferase
xref: UnificationXref9259
feature: FragmentFeature1660
cellular location: GO_0005829
comment: Reactome DB_ID: 5610780
display name: AK

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P53909
data source: Provenance1
name: Adenosine aminohydrolase
name: P53909
name: Adenosine deaminase
xref: UnificationXref9254
feature: FragmentFeature1659
cellular location: GO_0005829
comment: Reactome DB_ID: 5610265
display name: ADA

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P40361
data source: Provenance1
name: AMP deaminase 1 (EC 3.5.4.6) (Myoadenylate deaminase) (AMP deaminase isoform M)
name: Myoadenylate deaminase
name: AMP deaminase isoform M
name: P40361
name: myoadenylate deaminase
name: AMP deaminase 1
xref: UnificationXref9264
feature: FragmentFeature1661
cellular location: GO_0005829
comment: Reactome DB_ID: 5610625
display name: AMPD1

Homologues of AMPD1
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref9267
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5610630

Evidence602
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10559216
xref: http://identifiers.org/pubmed/17486099
xref: http://identifiers.org/pubmed/12944492
xref: http://identifiers.org/pubmed/9346902
xref: http://identifiers.org/pubmed/18573886
xref: http://identifiers.org/pubmed/14976220
xref: http://identifiers.org/pubmed/18240226
xref: http://identifiers.org/pubmed/15257295
xref: http://identifiers.org/pubmed/11124962
xref: http://identifiers.org/pubmed/12819195
xref: http://identifiers.org/pubmed/19074427
xref: http://identifiers.org/pubmed/8246982
xref: http://identifiers.org/pubmed/12819194
comment: AUF1 monomers form dimers which bind the U-rich sequences in AU-rich elements of mRNAs. Binding of the mRNA causes the dimers of AUF1 to form tetramers. Nonphosphorylated AUF1 isoform p40 causes the mRNA to form a rigid structure whereas p40 that is phosphorylated at serines 83 and 87 does not. This difference may cause nonphosphorylated p40 to fail to destabilize the bound mRNA.

Evidence601
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19412884
xref: http://identifiers.org/pubmed/15741316
xref: http://identifiers.org/pubmed/17560368
xref: http://identifiers.org/pubmed/19239886
xref: http://identifiers.org/pubmed/21755468
xref: http://identifiers.org/pubmed/16510870
xref: http://identifiers.org/pubmed/19165215
comment: In this module, the biology of various types of regulatory non-coding RNAs are described. Currently, biogenesis and functions of small interfering RNAs (siRNAs) and microRNAs are annotated.

Evidence604
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10205060
xref: http://identifiers.org/pubmed/15257295
xref: http://identifiers.org/pubmed/12136087
xref: http://identifiers.org/pubmed/11842200
comment: Ubiquitin-dependent proteolysis of AUF1 and nuclease-dependent destruction of AUF1-bound mRNA are coupled in an unknown way. It is possible that ubiquitinated AUF1 targets other members of the AUF1 and signal transduction regulated complex (ASTRC), such as polyA-binding protein, for degradation and this renders the mRNA susceptible to nucleases.

Evidence603
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10559216
xref: http://identifiers.org/pubmed/10205060
xref: http://identifiers.org/pubmed/12136087
xref: http://identifiers.org/pubmed/11842200
comment: AUF1 is ubiquitinated at unknown sites. The number of ubiquitin molecules conjugated to AUF1 and their linkage is unknown. Ubiquitination is required for subsequent degradation of both AUF1 and the mRNA bound by AUF1. It is uncertain if AUF1 is in a larger complex when it is ubiquitinated.

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P39567
data source: Provenance1
name: IMP (inosine monophosphate) dehydrogenase 1
name: Inosine-5'-monophosphate dehydrogenase 1 (EC 1.1.1.205) (IMP dehydrogenase 1) (IMPDH-I) (IMPD 1)
name: IMP dehydrogenase 1
name: P39567
name: IMPDH-I
name: Inosine-5'-monophosphate dehydrogenase 1
name: IMPD 1
xref: UnificationXref9203
feature: FragmentFeature1654
cellular location: GO_0005829
comment: Reactome DB_ID: 5610033
display name: IMPDH1

Evidence600
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15944707
xref: http://identifiers.org/pubmed/15364901
xref: http://identifiers.org/pubmed/17099701
xref: http://identifiers.org/pubmed/19330724
xref: http://identifiers.org/pubmed/17057362
xref: http://identifiers.org/pubmed/15372072
xref: http://identifiers.org/pubmed/14744438
xref: http://identifiers.org/pubmed/21755468
xref: http://identifiers.org/pubmed/19477631
xref: http://identifiers.org/pubmed/15211354
xref: http://identifiers.org/pubmed/19165215
xref: http://identifiers.org/pubmed/8252621
xref: http://identifiers.org/pubmed/15145345
xref: http://identifiers.org/pubmed/15525708
comment: Biogenesis of microRNAs (miRNAs) can be summarized in five steps (reviewed in Ketting 2011, Nowotny and Yang 2009, Kim et al. 2009, Chua et al. 2009, Hannon and He 2004): 1. Transcription. miRNA transcripts may come from autonomously transcribed genes, they may be contained in cotranscripts with other genes, or they may be located in introns of host genes. Most miRNAs are transcribed by RNA polymerase II, however a few miRNAs originate as RNA polymerase III cotranscripts with neighboring repetitive elements. The initial transcript, termed a primary microRNA (pri-miRNA), contains an imperfectly double-stranded region within a hairpin loop. Longer sequences extend from the 5' and 3' ends of the hairpin and may also contain double-stranded regions. 2. Cleavage by Drosha. The 5' and 3' ends of the pri-miRNA are removed during endoribonucleolytic cleavage by the Drosha nuclease in a complex with the RNA-binding protein DGCR8 (the Microprocessor complex). The cleavage product is a short hairpin of about 60 to 70 nt called the pre-microRNA (pre-miRNA). 3. Nuclear export by Exportin-5. The resulting pre-miRNA is bound by Exportin-5 in a complex with Ran and GTP. The complex translocates the pre-miRNA through the nuclear pore into the cytoplasm. 4. Cleavage by Dicer. Once in the cytoplasm the pre-miRNA is bound and cleaved by the Dicer ribonuclease in complex with the RNA-binding protein TRBP (TAR binding protein). The product is an imperfectly double-stranded miRNA of about 21 to 23 nucleotides. At this stage the double-stranded miRNA has protruding single-stranded 3' ends of 2-3 nt. 5. Strand selection and incorporation into RNA-Induced Silencing Complex (RISC). At this stage the miRNA has two strands: the passenger strand, which will be removed and degraded, and the guide strand, which will be retained and guides the RISC to target mRNAs. An Argonaute protein is already bound to the Dicer:miRNA complex or subsequently binds the complex (the order is unknown). The human ge…

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P50095
data source: Provenance1
name: IMP (inosine monophosphate) dehydrogenase 1
name: Inosine-5'-monophosphate dehydrogenase 1 (EC 1.1.1.205) (IMP dehydrogenase 1) (IMPDH-I) (IMPD 1)
name: IMP dehydrogenase 1
name: P50095
name: IMPDH-I
name: Inosine-5'-monophosphate dehydrogenase 1
name: IMPD 1
xref: UnificationXref9201
feature: FragmentFeature1653
cellular location: GO_0005829
comment: Reactome DB_ID: 5610029
display name: IMPDH1

Evidence609
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19729507
xref: http://identifiers.org/pubmed/15117938
xref: http://identifiers.org/pubmed/18367721
xref: http://identifiers.org/pubmed/12646273
xref: http://identifiers.org/pubmed/10330172
xref: http://identifiers.org/pubmed/12705825
xref: http://identifiers.org/pubmed/17369404
xref: http://identifiers.org/pubmed/12324455
xref: http://identifiers.org/pubmed/12639954
xref: http://identifiers.org/pubmed/17133347
comment: Tristetraprolin (TTP) binds UUAUUUAUU motifs in the AU-rich elements of mRNAs. TTP binds Transportin-1 (Importin beta-2) which plays a role in shuttling TTP between P-bodies and stress granules.

Evidence605
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12704645
xref: http://identifiers.org/pubmed/12440953
xref: http://identifiers.org/pubmed/18573886
xref: http://identifiers.org/pubmed/10205060
xref: http://identifiers.org/pubmed/16391004
xref: http://identifiers.org/pubmed/12819195
comment: AUF1 (hnRNP D0) dimers bind U-rich regions of AU-rich elements (AREs) in the 3' untranslated regions of mRNAs. The binding causes AUF1 dimers to assemble into higher order tetrameric complexes. Diphosphorylated AUF1 bound to RNA recruits additional proteins, including eIF4G, polyA-binding protein, Hsp, Hsc70, Hsp27, NSEP-1, NSAP-1, and IMP-2 which target the mRNA and AUF1 for degradation. Unphosphorylated AUF1 is thought to be less able to recruit additional proteins. AUF1 also interacts directly or indirectly with HuR and the RNA-induced silencing complex (RISC). AUF1 complexed with RNA and other proteins is ubiquitinated and targeted for destruction by the proteasome while the bound mRNA is degraded. Inhibition of ubiquitin addition to AUF1 blocks mRNA degradation. The mechanism by which ubiquitin-dependent proteolysis is coupled to mRNA degradation is unknown. At least 4 isoforms of AUF1 exist: p45 (45 kDa) contains all exons, p42 lacks exon 2, p40 lacks exon 7, and p37 lacks exons 2 and 7. The presence of exon 7 in p42 and p45 seems to block ubiquitination while the absence of exon 7 (p37 and p40) targets AUF1 for ubiquitination and destabilizes bound RNAs. Lack of exon 2 (p37 and p42) is associated with higher affinity for RNA and 14-3-3sigma (SFN). AUF1 binds and destabilizes mRNAs encoding Interleukin-1 beta (IL1B), Tumor Necrosis Factor alpha (TNFA), Cyclin-dependent kinase inhibitor 1 (CDNK1A, p21), Cyclin-D1 (CCND1), Granulocyte-macrophage colony stimulating factor (GM-CSF, CSF2), inducible Nitric oxide synthase (iNOS, NOS2), Proto-oncogene cFos (FOS), Myc proto-oncogene (MYC), Apoptosis regulator Bcl-2 (BCL2).

Evidence606
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17030608
xref: http://identifiers.org/pubmed/15538381
xref: http://identifiers.org/pubmed/18326031
xref: http://identifiers.org/pubmed/12198173
comment: Butyrate response factor 1 (BRF1) binds AU-rich elements in the 3' untranslated region of mRNAs.

Evidence607
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17030608
xref: http://identifiers.org/pubmed/15538381
xref: http://identifiers.org/pubmed/12198173
comment: BRF1 is phosphorylated at Serine92 and Serine203 by Protein kinase B/AKT. Protein kinase B is activated by phosphatidylinositol 3-kinase. Phosphorylation of BRF1 does not interfere with the ability of BRF1 to bind RNA or interact with enzymes that catalyze RNA degradation therefore larger complexes may contain phosphorylated BRF1.

Evidence608
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12704645
xref: http://identifiers.org/pubmed/12440953
xref: http://identifiers.org/pubmed/16391004
xref: http://identifiers.org/pubmed/15687258
xref: http://identifiers.org/pubmed/11719186
comment: Butyrate Response Factor 1 (BRF1, ZFP36L1, not to be confused with transcription factor IIIB) binds AU-rich elements in the 3' region of mRNAs. After binding, BRF1 recruits exonucleases (XRN1 and the exosome) and decapping enzymes (DCP1a and DCP2) to hydrolyze the RNA. The ability of BRF1 to direct RNA degradation is controlled by phosphorylation of BRF1. Protein kinase B/AKT1 phosphorylates BRF1 at serines 92 and 203. Phosphorylated BRF1 can still bind RNA but is sequestered by binding 14-3-3 protein, preventing BRF1 from destabilizing RNA. BRF1 is also phosphorylated by MK2 at serines 54, 92, 203, and at an unknown site in the C-terminus. It is unknown if this particular phosphorylated form of BRF1 binds 14-3-3.

p53-Independent G1/S DNA damage checkpoint
type: Pathway
data source: Provenance1
pathway component: REACT 259368.1
evidence: Evidence151
xref: UnificationXref1670
xref: UnificationXref1669
pathway order: PathwayStep147
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

RPL24B
type: ProteinReference
name: UniProt:P24000
xref: UnificationXref627
organism: http://identifiers.org/taxonomy/4932

Homologues of ATIC
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref9187
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5610051

ASASE
type: Protein
entity reference: Q05911
data source: Provenance1
name: Adenylosuccinase
name: Note: the coordinates are copied over from Homo sapiens.
name: Adenylosuccinate lyase
name: ADSL
name: Q05911
xref: UnificationXref9176
feature: FragmentFeature1648
cellular location: GO_0005829
comment: Reactome DB_ID: 5610060
display name: ASL

FGAM synthase
type: Protein
entity reference: P38972
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: FGAMS
name: Formylglycinamide ribotide synthetase
name: P38972
name: Phosphoribosylformylglycinamidine synthase
name: Formylglycinamide ribotide amidotransferase
name: FGARAT
xref: UnificationXref9158
feature: FragmentFeature1647
cellular location: GO_0005829
comment: Reactome DB_ID: 5610073
display name: PFAS

phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase
type: Protein
entity reference: P07244
data source: Provenance1
name: GAR transformylase
name: Trifunctional purine biosynthetic protein adenosine-3 (Includes: Phosphoribosylamine--glycine ligase (EC 6.3.4.13) (GARS) (Glycinamide ribonucleotide synthetase) (Phosphoribosylglycinamide synthetase); Phosphoribosylformylglycinamidine cyclo-ligase (EC 6.3.3.1) (AIRS) (Phosphoribosyl-aminoimidazole synthetase) (AIR synthase); Phosphoribosylglycinamide formyltransferase (EC 2.1.2.2) (GART) (GAR transformylase) (5'-phosphoribosylglycinamide transformylase))
name: Trifunctional purine biosynthetic protein adenosine-3
name: GARS
name: AIRS
name: 5'-phosphoribosylglycinamide transformylase
name: Phosphoribosylamine--glycine ligase
name: Glycinamide ribonucleotide synthetase
name: Note: the coordinates are copied over from Homo sapiens.
name: AIR synthase
name: Phosphoribosylformylglycinamidine cyclo-ligase
name: Phosphoribosylglycinamide formyltransferase
name: Phosphoribosyl-aminoimidazole synthetase
name: P07244
name: Phosphoribosylglycinamide synthetase
xref: UnificationXref9143
feature: FragmentFeature1646
cellular location: GO_0005829
comment: Reactome DB_ID: 5610067
display name: GART

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P50094
data source: Provenance1
name: IMP (inosine monophosphate) dehydrogenase 1
name: Inosine-5'-monophosphate dehydrogenase 1 (EC 1.1.1.205) (IMP dehydrogenase 1) (IMPDH-I) (IMPD 1)
name: IMP dehydrogenase 1
name: P50094
name: IMPDH-I
name: Inosine-5'-monophosphate dehydrogenase 1
name: IMPD 1
xref: UnificationXref9197
feature: FragmentFeature1651
cellular location: GO_0005829
comment: Reactome DB_ID: 5610021
display name: IMPDH1

Homologues of IMPDH1
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref9206
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5610038

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38009
data source: Provenance1
name: Inosinicase
name: Bifunctional purine biosynthesis protein PURH (Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase (EC 2.1.2.3) (AICAR transformylase); IMP cyclohydrolase (EC 3.5.4.10) (Inosinicase) (IMP synthetase) (ATIC))
name: 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase
name: IMP cyclohydrolase
name: Bifunctional purine biosynthesis protein PURH
name: P38009
name: IMP synthetase
name: AICAR transformylase
name: Phosphoribosylaminoimidazolecarboxamide formyltransferase
xref: UnificationXref9186
feature: FragmentFeature1650
cellular location: GO_0005829
comment: Reactome DB_ID: 5610050
display name: ATIC

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P54113
data source: Provenance1
name: Inosinicase
name: P54113
name: Bifunctional purine biosynthesis protein PURH (Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase (EC 2.1.2.3) (AICAR transformylase); IMP cyclohydrolase (EC 3.5.4.10) (Inosinicase) (IMP synthetase) (ATIC))
name: 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase
name: IMP cyclohydrolase
name: Bifunctional purine biosynthesis protein PURH
name: IMP synthetase
name: AICAR transformylase
name: Phosphoribosylaminoimidazolecarboxamide formyltransferase
xref: UnificationXref9184
feature: FragmentFeature1649
cellular location: GO_0005829
comment: Reactome DB_ID: 5610046
display name: ATIC

Evidence615
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17517897
xref: http://identifiers.org/pubmed/11834731
xref: http://identifiers.org/pubmed/11018049
xref: http://identifiers.org/pubmed/16484227
xref: http://identifiers.org/pubmed/14981256
comment: HuR binds AU-rich elements of mRNAs. Bound HuR can form oligomers on longer AU-rich elements. Phosphorylated HuR binds mRNA more tightly than unphosphorylated HuR does.

Evidence614
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/20086103
xref: http://identifiers.org/pubmed/18285462
comment: HuR phosphorylated on ser221 and ser318 binds AU-rich regions of mRNAs. Phosphorylation on ser318 appears to affect RNA binding and phosphorylation of ser221 affects nucleocytoplasmic shuttling.

Evidence613
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17392515
comment: HuR (ELAV1) phosphorylated on serine221 and serine158 binds COX-2 mRNA in the nucleus. The phosphorylation of serine 158 appears to affect RNA-binding while phosphorylation on serine 221 affects nucleocytoplasmic shuffling.

Evidence612
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18285462
comment: Protein kinase C delta (PKCdelta) phosphorylates HuR (ELAVL1) at serine 221 and serine 318.

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P04046
data source: Provenance1
name: GPAT
name: Glutamine phosphoribosylpyrophosphate amidotransferase
name: Amidophosphoribosyltransferase precursor (EC 2.4.2.14) (Glutamine phosphoribosylpyrophosphate amidotransferase) (ATASE) (GPAT)
name: ATASE
name: Amidophosphoribosyltransferase precursor
name: phosphoribosyl pyrophosphate amidotransferase
name: P04046
name: glutamine phosphoribosylpyrophosphate amidotransferase
name: amidophosphoribosyltransferase
xref: UnificationXref9120
feature: FragmentFeature1645
cellular location: GO_0005829
comment: Reactome DB_ID: 5610083
display name: PPAT

Evidence611
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17392515
comment: Protein kinase C alpha (PKCalpha) phosphorylates HuR (ELAVL1) on serine221 and serine 158.

Evidence610
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12704645
xref: http://identifiers.org/pubmed/12440953
xref: http://identifiers.org/pubmed/16391004
xref: http://identifiers.org/pubmed/18481987
comment: Tristetraproline (TTP) binds RNAs that contain AU-rich elements and recruits enzymes that degrade RNA. TTP interacts with the exosome (3' to 5' exonuclease), XRN1 (5' to 3' exonuclease), and the decapping enzymes DCP1 and DCP2a. The activity of TTP is regulated by phosphorylation. MK2 phosphorylates TTP, which then binds 14-3-3.The interaction with 14-3-3 prevents phosphorylated TTP from entering stress granules and stabilizes mRNA bound by phosphorylated TTP. Tristetraproline is known to bind AU-rich elements in the following mRNAs: Tumor necrosis factor alpha (TNFA), Granulocyte-macrophage colony stimulating factor (CSF2, GM-CSF), Interleukin-2 (IL-2), and Proto-oncogene C-FOS (FOS, c-fos). Mice deficient in TTP exhibit arthritis, weight loss, skin lesions, autoimmunity, and myeloid hyperplasia.

Evidence618
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: PublicationXref1490
comment: 80S monosomes dissociate into 40S and 60S ribosomal subunits. eIF1A promotes this dissociation.

Evidence619
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: The 80S ribosome dissociates into free 40S (small) and 60S (large) ribosomal subunits. Each ribosomal subunit is constituted by several individual ribosomal proteins and rRNA.

Evidence616
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12704645
xref: http://identifiers.org/pubmed/12440953
xref: http://identifiers.org/pubmed/18285462
xref: http://identifiers.org/pubmed/14976220
xref: http://identifiers.org/pubmed/16391004
xref: http://identifiers.org/pubmed/17392515
comment: HuR (ELAVL1) is a ubiquitous protein that binds AU-rich elements in mRNAs and acts to stabilize the mRNAs. HuR activity is controlled by phosphorylation, with PKC alpha and PCK delta enhancing the ability of HuR to bind and stabilize mRNAs. Binding of mRNAs occurs in the nucleus and HuR then interacts with the CRM1 export pathway to transfer the mRNA to the cytoplasm. The mechanism by which HuR shields the mRNA from degradation is unknown. HuR also regulates translation of some mRNAs, in some cases repressing translation and in some cases enhancing translation of bound mRNAs by recruiting them to polysomes. HuR binds and regulates mRNAs encoding Cyclooxygenase-2 (COX2, PTGS2), Cyclin A (CCNA, CCNA2), Cyclin D1 (CCND1), Cyclin B1 (CCNB1), CD83 antigen (CD83), and proto-oncogene c-Fos (FOS). HuR is a member of a family of proteins that also contains HuD (ELAVL4), HuB (ELAVL2), and HuC (ELAVL3). HuB, HuC, and HuD are specifically expressed in neural tissue. HuR participates in apoptosis. During lethal stress HuR becomes mostly cytoplasmic and is a target of Caspase-3 and Caspase-7. The cleavage products of HuR in turn promote apoptosis.

Evidence617
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15460540
xref: http://identifiers.org/pubmed/12704645
xref: http://identifiers.org/pubmed/12440953
xref: http://identifiers.org/pubmed/16391004
comment: RNA elements rich in adenine and uracil residues (AU-rich elements) bind specific proteins which either target the RNA for degradation or, more rarely, stabilize the RNA. The activity of the AU-element binding proteins is regulated, usually by phosphorylation but also by subcellular localization.

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: O42831
data source: Provenance1
name: IMP (inosine monophosphate) dehydrogenase 1
name: Inosine-5'-monophosphate dehydrogenase 1 (EC 1.1.1.205) (IMP dehydrogenase 1) (IMPDH-I) (IMPD 1)
name: IMP dehydrogenase 1
name: O42831
name: IMPDH-I
name: Inosine-5'-monophosphate dehydrogenase 1
name: IMPD 1
xref: UnificationXref9199
feature: FragmentFeature1652
cellular location: GO_0005829
comment: Reactome DB_ID: 5610025
display name: IMPDH1

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P46681
data source: Provenance1
name: P46681
name: D-2-hydroxyglutarate dehydrogenase
xref: UnificationXref9062
feature: FragmentFeature1642
cellular location: GO_0005759
comment: Reactome DB_ID: 5615237
display name: D2HGDH

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P39976
data source: Provenance1
name: P39976
name: D-2-hydroxyglutarate dehydrogenase
xref: UnificationXref9060
feature: FragmentFeature1641
cellular location: GO_0005759
comment: Reactome DB_ID: 5615233
display name: D2HGDH

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P42940
data source: Provenance1
name: Electron Transfer Flavoprotein beta subunit
name: P42940
name: ETF-beta
xref: UnificationXref9099
feature: FragmentFeature1643
cellular location: GO_0005759
comment: Reactome DB_ID: 5611719
display name: ETFB

P10127
type: Protein
entity reference: P10127
data source: Provenance1
xref: UnificationXref9077
cellular location: GO_0005759
comment: Reactome DB_ID: 5615227

Succinate dehydrogenase (ubiquinone) iron-sulfur protein, mitochondrial
type: Protein
entity reference: P21801
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: SDHB
name: Succinate Dehydrogenase complex subunit B
name: P21801
name: Iron-sulfur subunit of complex II
xref: UnificationXref9041
feature: FragmentFeature1639
cellular location: GO_0005743
comment: Reactome DB_ID: 5608719
display name: Ip

P33421
type: Protein
entity reference: P33421
data source: Provenance1
name: Succinate Dehydrogenase complex subunit C
name: Note: the coordinates are copied over from Homo sapiens.
name: Succinate dehydrogenase complex subunit C
name: CYBL
name: QPS1
name: Succinate-ubiquinone oxidoreductase cytochrome B large subunit
name: Succinate dehydrogenase cytochrome b560 subunit, mitochondrial precursor
name: Integral membrane protein CII-3
name: QPs-1
xref: UnificationXref9036
feature: FragmentFeature1638
cellular location: GO_0005743
comment: Reactome DB_ID: 5608728
display name: SDHC

Homologues of D2HGDH
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref9063
cellular location: GO_0005759
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5615238

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P08417
data source: Provenance1
name: P08417
name: Fumarase
name: fumarate hydratase
name: Fumarate hydratase, mitochondrial
xref: UnificationXref9047
feature: FragmentFeature1640
cellular location: GO_0005759
comment: Reactome DB_ID: 5608702
display name: FH

http://identifiers.org/pubmed/8163052
type: PublicationXref
id: 8163052
author: Gomis, R
author: Malaisse, WJ
author: Sener, A
author: Fernandez-Alvarez, J
author: Conget, I
author: Rasschaert, J
db: Pubmed
title: Enzymatic, metabolic and secretory patterns in human islets of type 2 (non-insulin-dependent) diabetic patients
source: Diabetologia 37:177-81
year: 1994

http://identifiers.org/pubmed/15080793
type: PublicationXref
id: 15080793
author: Wenk, MR
author: De Camilli, Pietro
author: Uhlén, P
author: Lee, E
author: Ehrlich, BE
author: Degray, B
author: Johenning, FW
db: Pubmed
title: InsP3-mediated intracellular calcium signalling is altered by expression of synaptojanin-1
source: Biochem J 382:687-94
year: 2004

Q12480
type: Protein
entity reference: Q12480
data source: Provenance1
xref: UnificationXref9101
cellular location: GO_0005759
comment: Reactome DB_ID: 5611715

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: Q08822
data source: Provenance1
name: Q08822
xref: UnificationXref9107
feature: FragmentFeature1644
cellular location: GO_0005759
comment: Reactome DB_ID: 5611727
display name: ETFDH

SDHA
type: Protein
entity reference: UniProt:Q00711
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Flavoprotein subunit of complex II
name: Succinate Dehydrogenase complex subunit A
name: Succinate dehydrogenase (ubiquinone) flavoprotein subunit, mitochondrial
name: Q00711
xref: UnificationXref9028
feature: FragmentFeature1635
cellular location: GO_0005743
comment: Reactome DB_ID: 5608709
display name: Fp

Homologues of SDHA
type: Protein
data source: Provenance1
member physical entity: SDHA
xref: UnificationXref9031
cellular location: GO_0005743
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5608714

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P53312
data source: Provenance1
name: Succinyl-CoA synthetase, betaA chain
name: P53312
xref: UnificationXref9020
feature: FragmentFeature1634
cellular location: GO_0005759
comment: Reactome DB_ID: 5608741
display name: SUCLA2

http://identifiers.org/pubmed/15359280
type: PublicationXref
id: 15359280
author: Truscott, KN
author: Chacinska, A
author: Guiard, B
author: Meisinger, C
author: Kozjak, V
author: Pfannschmidt, S
author: Schulze-Specking, A
author: Sanjuán Szklarz, LK
author: Pfanner, N
author: Wiedemann, N
db: Pubmed
title: Essential role of Mia40 in import and assembly of mitochondrial intermembrane space proteins
source: EMBO J 23:3735-46
year: 2004

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P53598
data source: Provenance1
name: P53598
name: Succinyl-CoA synthetase, alpha-chain
xref: UnificationXref9018
feature: FragmentFeature1633
cellular location: GO_0005759
comment: Reactome DB_ID: 5608737
display name: SUCLG1

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P20967
data source: Provenance1
name: 2-oxoglutarate dehydrogenase E1 component, mitochondrial precursor
name: P20967
name: 2-oxoglutarate dehydrogenase E1
name: ODO1_HUMAN
name: Alpha-ketoglutarate dehydrogenase
name: alpha-ketoglutarate dehydrogenase E1 apoenzyme
xref: UnificationXref9011
feature: FragmentFeature1632
cellular location: GO_0005759
comment: Reactome DB_ID: 5608748
display name: OGDH

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P19262
data source: Provenance1
name: alpha-ketoglutarate dehydrogenase E2
name: P19262
name: Dihydrolipoamide succinyltransferase
name: Lipo-DLST
xref: UnificationXref9005
feature: ModificationFeature319
feature: FragmentFeature1631
cellular location: GO_0005759
comment: Reactome DB_ID: 5608755
display name: DLST

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P53982
data source: Provenance1
name: Isocitrate dehydrogenase 2 (NADP), mitochondrial
name: P53982
xref: UnificationXref8996
feature: FragmentFeature1630
cellular location: GO_0005759
comment: Reactome DB_ID: 5614855
display name: IDH2

Eukaryotic Translation Termination
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction337
pathway component: BiochemicalReaction338
pathway component: BiochemicalReaction336
evidence: Evidence655
xref: UnificationXref4460
xref: UnificationXref4461
xref: RelationshipXref124
pathway order: PathwayStep644
pathway order: PathwayStep642
pathway order: PathwayStep643
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

Succinate Dehydrogenase complex subunit C
type: Protein
entity reference: Q04487
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Succinate dehydrogenase complex subunit C
name: Q04487
name: CYBL
name: QPS1
name: Succinate-ubiquinone oxidoreductase cytochrome B large subunit
name: Succinate dehydrogenase cytochrome b560 subunit, mitochondrial precursor
name: Integral membrane protein CII-3
name: QPs-1
xref: UnificationXref9034
feature: FragmentFeature1637
cellular location: GO_0005743
comment: Reactome DB_ID: 5608724
display name: SDHC

SDHA
type: Protein
entity reference: P47052
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Flavoprotein subunit of complex II
name: P47052
name: Succinate Dehydrogenase complex subunit A
name: Succinate dehydrogenase (ubiquinone) flavoprotein subunit, mitochondrial
xref: UnificationXref9030
feature: FragmentFeature1636
cellular location: GO_0005743
comment: Reactome DB_ID: 5608713
display name: Fp

Homologues of SDHC
type: Protein
data source: Provenance1
member physical entity: P33421
member physical entity: Succinate Dehydrogenase complex subunit C
xref: UnificationXref9037
cellular location: GO_0005743
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5608729

http://identifiers.org/pubmed/10843998
type: PublicationXref
id: 10843998
author: Koduru, SB
author: Hamada, M
author: Sakulich, AL
author: Maraia, RJ
db: Pubmed
title: Transcription termination by RNA polymerase III in fission yeast. A genetic and biochemically tractable model system.
source: J Biol Chem 275:29076-81
year: 2000

UniProt:P14242
type: ProteinReference
name: PMS1
xref: UnificationXref11677
organism: http://identifiers.org/taxonomy/4932

http://identifiers.org/pubmed/12640110
type: PublicationXref
id: 12640110
author: Rapaport, D
author: Neupert, W
author: Brix, J
author: Stan, T
author: Schneider-Mergener, J
author: Pfanner, N
db: Pubmed
title: Mitochondrial protein import: recognition of internal import signals of BCS1 by the TOM complex
source: Mol Cell Biol 23:2239-50
year: 2003

http://identifiers.org/pubmed/12482742
type: PublicationXref
id: 12482742
author: Busse, R
author: Fleming, I
db: Pubmed
title: Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase
source: Am J Physiol Regul Integr Comp Physiol 284:R1-12
year: 2003

ENA5
type: ProteinReference
name: UniProt:Q12691
xref: UnificationXref57
organism: http://identifiers.org/taxonomy/4932

RPL13A
type: ProteinReference
name: UniProt:Q12690
xref: UnificationXref596
organism: http://identifiers.org/taxonomy/4932

http://identifiers.org/pubmed/6434529
type: PublicationXref
id: 6434529
author: Chuang, DT
author: Cox, RP
author: Markovitz, PJ
db: Pubmed
title: Familial hyperlysinemias. Purification and characterization of the bifunctional aminoadipic semialdehyde synthase with lysine-ketoglutarate reductase and saccharopine dehydrogenase activities.
source: J Biol Chem 259:11643-6
year: 1984

http://identifiers.org/pubmed/8946167
type: PublicationXref
id: 8946167
author: Blanch, L
author: Anson, D S
author: Hopwood, J J
author: Scott, H S
author: Guo, X H
author: Karageorgos, L E
author: Weber, B
db: Pubmed
title: Structure and sequence of the human sulphamidase gene
source: DNA Res. 3:269-71
year: 1996

http://identifiers.org/pubmed/22910329
type: PublicationXref
id: 22910329
author: Marinelli, Raúl Alberto
author: Carnovale, Cristina Ester
author: Marchissio, Maria Julia
author: Francés, Daniel Eleazar Antonio
db: Pubmed
title: Mitochondrial aquaporin-8 knockdown in human hepatoma HepG2 cells causes ROS-induced mitochondrial depolarization and loss of viability
source: Toxicol. Appl. Pharmacol. 264:246-54
year: 2012

http://identifiers.org/pubmed/11447121
type: PublicationXref
id: 11447121
author: Morimoto, R I
author: Eriksson, J E
author: MacKintosh, C
author: Mikhailov, A
author: Hietakangas, V
author: Kallio, M
author: Sistonen, L
author: Morrice, N
author: Rantanen, J O
author: Hellman, J
author: Meinander, A
author: Holmberg, C I
db: Pubmed
title: Phosphorylation of serine 230 promotes inducible transcriptional activity of heat shock factor 1
source: EMBO J. 20:3800-10
year: 2001

UniProt:P28000 RPC19
type: ProteinReference
name: RPC19
name: N1937
name: YNL113W
xref: UnificationXref935
comment: MISCELLANEOUS Present with 8680 molecules/cell in log phase SD medium.SIMILARITY Belongs to the archaeal RpoL/eukaryotic RPB11/RPC19 RNA polymerase subunit family.
organism: http://identifiers.org/taxonomy/4932

http://identifiers.org/pubmed/8755247
type: PublicationXref
id: 8755247
author: Migliaccio, E
author: Bonfini, L
author: Pelicci, PG
author: Pelicci, G
author: Lanfrancone, L
db: Pubmed
title: Not all Shc's roads lead to Ras
source: Trends Biochem Sci 21:257-61
year: 1996

Transport to the Golgi and subsequent modification
type: Pathway
data source: Provenance1
pathway component: REACT 232878.1
evidence: Evidence734
xref: UnificationXref5057
xref: UnificationXref5058
pathway order: PathwayStep721
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

http://identifiers.org/pubmed/9469823
type: PublicationXref
id: 9469823
author: Watanabe, H
author: Gu, L
author: Hong, Y
author: Li, G M
author: McCulloch, S
db: Pubmed
title: ATP-dependent interaction of human mismatch repair proteins and dual role of PCNA in mismatch repair
source: Nucleic Acids Res. 26:1173-8
year: 1998

http://identifiers.org/pubmed/11742412
type: PublicationXref
id: 11742412
author: Saltiel, AR
author: Kahn, CR
db: Pubmed
title: Insulin signalling and the regulation of glucose and lipid metabolism
source: Nature 414:799-806
year: 2001

8-oxoguanine [ChEBI:29116]
type: SmallMoleculeReference
name: 8-oxoguanine
xref: UnificationXref11352

http://identifiers.org/pubmed/18660845
type: PublicationXref
id: 18660845
author: Zhao, FQ
author: Keating, AF
db: Pubmed
title: Functional properties and genomics of glucose transporters
source: Curr Genomics 8:113-28
year: 2007

http://identifiers.org/pubmed/22615488
type: PublicationXref
id: 22615488
author: Hahn, Yoonsoo
author: Baek, Hee Jo
author: Son, Hye-Ju
author: Kook, Hyun
author: Kee, Hae Jin
author: Pak, Jhang Ho
author: Chakravarti, Debabrata
author: Eom, Gwang Hyeon
author: Kook, Hoon
author: Seo, Sang-Beom
author: Kim, Ji-Young
author: Choe, Nakwon
author: Kim, Kee-Beom
author: Oh, Si-Taek
author: Kim, Dong-Wook
db: Pubmed
title: KDM3B is the H3K9 demethylase involved in transcriptional activation of lmo2 in leukemia
source: Mol. Cell. Biol. 32:2917-33
year: 2012

DNF3
type: ProteinReference
name: UniProt:Q12674
xref: UnificationXref11242
organism: http://identifiers.org/taxonomy/4932

DNF2
type: ProteinReference
name: UniProt:Q12675
xref: UnificationXref11234
organism: http://identifiers.org/taxonomy/4932

RPL21B
type: ProteinReference
name: UniProt:Q12672
xref: UnificationXref643
organism: http://identifiers.org/taxonomy/4932

http://identifiers.org/pubmed/12669019
type: PublicationXref
id: 12669019
author: Desjardins, M
db: Pubmed
title: ER-mediated phagocytosis: a new membrane for new functions
source: Nat Rev Immunol 3:280-91
year: 2003

ChEBI:29265 Asn-tRNA(Asn)
type: SmallMoleculeReference
name: Asn-tRNA(Asn)
xref: UnificationXref3761

http://identifiers.org/pubmed/6434534
type: PublicationXref
id: 6434534
author: Gracy, RW
author: Yuan, PM
author: Lu, HS
db: Pubmed
title: Primary structure of human triosephosphate isomerase
source: J Biol Chem 259:11958-68
year: 1984

http://identifiers.org/pubmed/15274629
type: PublicationXref
id: 15274629
author: Takeuchi, N
author: Heck, A
author: Spencer, AC
author: Watanabe, K
author: Spremulli, LL
db: Pubmed
title: Characterization of the human mitochondrial methionyl-tRNA synthetase
source: Biochemistry 43:9743-54
year: 2004

http://identifiers.org/pubmed/7354069
type: PublicationXref
id: 7354069
author: Anderson, PM
author: Desnick, RJ
db: Pubmed
title: Purification and properties of uroporphyrinogen I synthase from human erythrocytes. Identification of stable enzyme-substrate intermediates.
source: J Biol Chem 255:1993-9
year: 1980

http://identifiers.org/pubmed/17331073
type: PublicationXref
id: 17331073
author: Wei, Y
author: Hornemann, T
author: von Eckardstein, A
db: Pubmed
title: Is the mammalian serine palmitoyltransferase a high-molecular-mass complex?
source: Biochem J 405:157-64
year: 2007

http://identifiers.org/pubmed/14739303
type: PublicationXref
id: 14739303
author: Su, Xiaoqin
author: Shu, Hong-Bing
author: Han, Ke-Jun
author: Zhang, Jun
author: Bin, Liang-Hua
author: Xu, Liang-Guo
db: Pubmed
title: Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways
source: J. Biol. Chem. 279:15652-61
year: 2004

http://identifiers.org/pubmed/7354072
type: PublicationXref
id: 7354072
author: Bodlaender, P
author: Shemin, D
author: Bevan, DR
db: Pubmed
title: Mechanism of porphobilinogen synthase. Requirement of Zn2+ for enzyme activity.
source: J Biol Chem 255:2030-5
year: 1980

MPS IIIC - Sanfilippo syndrome C
type: Pathway
data source: Provenance1
pathway component: REACT 227287.2
evidence: Evidence885
xref: UnificationXref5945
xref: UnificationXref5946
pathway order: PathwayStep865
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

http://identifiers.org/pubmed/12515382
type: PublicationXref
id: 12515382
author: Arndt-Jovin, DJ
author: Ingelfinger, D
author: Achsel, T
author: Lührmann, R
db: Pubmed
title: The human LSm1-7 proteins colocalize with the mRNA-degrading enzymes Dcp1/2 and Xrnl in distinct cytoplasmic foci
source: RNA 8:1489-501
year: 2002

UnificationXref1781
type: UnificationXref
id: 5611783
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611783

UnificationXref1780
type: UnificationXref
id: 5611782
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611782

UnificationXref1783
type: UnificationXref
id: 5611785
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611785

UnificationXref1782
type: UnificationXref
id: 5611784
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611784

UnificationXref1785
type: UnificationXref
id: 5611787
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611787

UnificationXref1784
type: UnificationXref
id: 5611786
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611786

UnificationXref1786
type: UnificationXref
id: 5611788
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611788

UnificationXref1787
type: UnificationXref
id: 5611790
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611790

UnificationXref1788
type: UnificationXref
id: 5611791
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611791

UnificationXref1789
type: UnificationXref
id: 5611792
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611792

Transcriptional regulation of white adipocyte differentiation
type: Pathway
data source: Provenance1
pathway component: TemplateReaction10
pathway component: TemplateReaction9
evidence: Evidence256
xref: UnificationXref2146
xref: UnificationXref2145
pathway order: PathwayStep250
pathway order: PathwayStep251
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref1792
type: UnificationXref
id: 5611809
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611809

Metabolism of seratonin
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction415
evidence: Evidence803
xref: UnificationXref5410
xref: UnificationXref5409
pathway order: PathwayStep789
display name: Metabolism of serotonin
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref1791
type: UnificationXref
id: 5611808
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611808

UnificationXref1790
type: UnificationXref
id: REACT_192060
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_192060.3

UnificationXref1796
type: UnificationXref
id: 5610132
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610132

UnificationXref1795
type: UnificationXref
id: Q03290
db: UniProt

UnificationXref1794
type: UnificationXref
id: 5610128
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610128

UnificationXref1793
type: UnificationXref
id: P37366
db: UniProt

UnificationXref1799
type: UnificationXref
id: 5610133
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610133

UnificationXref1797
type: UnificationXref
id: P06242
db: UniProt

UnificationXref1798
type: UnificationXref
id: 5610124
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610124

NGF signalling via TRKA from the plasma membrane
type: Pathway
data source: Provenance1
pathway component: REACT 254325.1
pathway component: REACT 263239.1
pathway component: REACT 258979.1
pathway component: REACT 251816.1
pathway component: REACT 248688.1
evidence: Evidence417
xref: UnificationXref2925
xref: UnificationXref2926
pathway order: PathwayStep403
pathway order: PathwayStep402
pathway order: PathwayStep405
pathway order: PathwayStep409
pathway order: PathwayStep408
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

Nicotinate metabolism
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction570
pathway component: BiochemicalReaction569
pathway component: BiochemicalReaction568
pathway component: BiochemicalReaction572
pathway component: BiochemicalReaction567
pathway component: BiochemicalReaction571
evidence: Evidence1033
xref: UnificationXref6907
xref: UnificationXref6906
xref: RelationshipXref680
pathway order: PathwayStep1015
pathway order: PathwayStep1014
pathway order: PathwayStep1017
pathway order: PathwayStep1016
pathway order: PathwayStep1013
pathway order: PathwayStep1012
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref589
type: UnificationXref
id: P0C2H6
db: UniProt

UnificationXref587
type: UnificationXref
id: P49167
db: UniProt

UnificationXref588
type: UnificationXref
id: 5609796
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609796

UnificationXref581
type: UnificationXref
id: 5609860
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609860

UnificationXref582
type: UnificationXref
id: 5609861
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609861

UnificationXref580
type: UnificationXref
id: P0CX46
db: UniProt

UnificationXref585
type: UnificationXref
id: P26321
db: UniProt

UnificationXref586
type: UnificationXref
id: 5609825
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609825

UnificationXref583
type: UnificationXref
id: P04650
db: UniProt

UnificationXref584
type: UnificationXref
id: 5609800
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609800

http://identifiers.org/pubmed/9548747
type: PublicationXref
id: 9548747
author: Hammond, PW
author: Cech, TR
db: Pubmed
title: Euplotes telomerase: evidence for limited base-pairing during primer elongation and dGTP as an effector of translocation
source: Biochemistry 37:5162-72
year: 1998

UnificationXref598
type: UnificationXref
id: P40212
db: UniProt

UnificationXref599
type: UnificationXref
id: 5609587
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609587

UnificationXref590
type: UnificationXref
id: 5609703
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609703

Inflammasomes
type: Pathway
data source: Provenance1
pathway component: REACT 189238.3
evidence: Evidence325
xref: UnificationXref2501
xref: UnificationXref2500
pathway order: PathwayStep318
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref591
type: UnificationXref
id: P0C2H7
db: UniProt

UnificationXref592
type: UnificationXref
id: 5609707
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609707

UnificationXref593
type: UnificationXref
id: 5609708
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609708

UnificationXref594
type: UnificationXref
id: P14120
db: UniProt

UnificationXref595
type: UnificationXref
id: 5609725
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609725

UnificationXref596
type: UnificationXref
id: Q12690
db: UniProt

UnificationXref597
type: UnificationXref
id: 5609583
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609583

http://identifiers.org/pubmed/9045610
type: PublicationXref
id: 9045610
author: Weaver, PL
author: Chuang, RY
author: Chang, TH
author: Liu, Z
db: Pubmed
title: Requirement of the DEAD-Box protein ded1p for messenger RNA translation.
source: Science 275:1468-71
year: 1997

UnificationXref11066
type: UnificationXref
id: REACT_175433
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_175433.3

UnificationXref992
type: UnificationXref
id: 981779
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=981779

UnificationXref3633
type: UnificationXref
id: 5610675
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610675

Evidence545
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9409616
comment: In addition to the methylation of the 5'-cap, there is methylation of internal nucleotides in the mRNA. This methylation can occur in translated and untranslated regions. One to three methyl groups have been seen per mRNA molecule, but methylation is non-stoichiometric. The most frequent methylation observed is at the N6 position of adenosine. The function of mRNA internal methylation, if any, is unknown.

UnificationXref11067
type: UnificationXref
id: 5615149
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615149

UnificationXref993
type: UnificationXref
id: REACT_27657
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27657.1

UnificationXref3632
type: UnificationXref
id: 5610674
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610674

Evidence544
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11017188
xref: http://identifiers.org/pubmed/10395561
xref: http://identifiers.org/pubmed/3326038
xref: http://identifiers.org/pubmed/11909521
comment: The 5'-ends of all eukaryotic pre-mRNAs studied thus far are converted to cap structures. The cap is thought to influence splicing of the first intron, and is bound by 'cap-binding' proteins, CBP80 and CBP20, in the nucleus. The cap is important for translation initiation, and it also interacts with the poly(A)terminus, via proteins, resulting in circularization of the mRNA to facilitate multiple rounds of translation. The cap is also important for mRNA stability, protecting it from 5' to 3' nucleases, and is required for mRNA export to the cytoplasm. The capping reaction usually occurs very rapidly on nascent transcripts; after the synthesis of only a few nucleotides by RNA polymerase II. The capping reaction involves the conversion of the 5'-end of the nascent transcript from a triphosphate to a diphosphate by a RNA 5'-triphosphatase, followed by the addition of a guanosine monophosphate by the mRNA guanylyltransferase, to form a 5'-5'-triphosphate linkage. This cap is then methylated by 2'-O-methyltransferases.

UnificationXref11068
type: UnificationXref
id: REACT_175358
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_175358.3

UnificationXref990
type: UnificationXref
id: 981775
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=981775

UnificationXref3631
type: UnificationXref
id: REACT_5617
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5617.1

Evidence543
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: At the beginning of this reaction, 1 molecule of 'CBP80', and 1 molecule of 'CBP20' are present. At the end of this reaction, 1 molecule of 'Cap Binding Complex (CBC)' is present. This reaction takes place in the 'nucleus'.

UnificationXref11069
type: UnificationXref
id: CHEBI:18243
db: ChEBI

UnificationXref991
type: UnificationXref
id: REACT_27454
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27454.1

UnificationXref3630
type: UnificationXref
id: 29626
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29626

Evidence542
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: The cap binding complex binds to the methylated GMP cap on the nascent mRNA transcript.

UnificationXref11062
type: UnificationXref
id: 5615134
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615134

Evidence549
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: At the beginning of this reaction, 1 molecule of 'ATAC C Complex with lariat containing 5'-end cleaved mRNA' is present. At the end of this reaction, 1 molecule of 'U6 ATAC snRNP', 1 molecule of 'post exon ligation complex', 1 molecule of 'U12 snRNP', 1 molecule of 'U11 snRNP', and 1 molecule of 'U5 snRNP' are present. This reaction takes place in the 'nucleus'.

UnificationXref11063
type: UnificationXref
id: GO:0005765
db: GENE ONTOLOGY

Evidence548
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: At the beginning of this reaction, 1 molecule of 'ATAC C Complex' is present. At the end of this reaction, 1 molecule of 'ATAC C Complex with lariat containing 5'-end cleaved mRNA' is present. This reaction takes place in the 'nucleus'.

UnificationXref11064
type: UnificationXref
id: 5615135
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615135

Evidence547
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: At the beginning of this reaction, 1 molecule of 'ATAC B Complex' is present. At the end of this reaction, 1 molecule of 'U4 ATAC snRNP', and 1 molecule of 'ATAC C Complex' are present. This reaction takes place in the 'nucleus'.

UnificationXref11065
type: UnificationXref
id: 5615137
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615137

Evidence546
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: The U4atac/U6atac enters the spliceosome and U6atac snRNA forms base pairing interactions with the 5' ss and also forms base pairing interactions with U12 and U4atac is partially displaced. U5 snRNP, the only snRNP common to both the major and minor splicing pathways, also joins the spliceosome to form the B complex and interacts with nucleotides within the 3' end of the exon flanking the 5' ss.

UnificationXref998
type: UnificationXref
id: 981778
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=981778

UnificationXref999
type: UnificationXref
id: REACT_27822
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27822.2

UnificationXref996
type: UnificationXref
id: 912367
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=912367

Evidence541
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9790902
comment: In the final step of the capping reaction, the methyltransferase takes a methyl group from S-adenosyl-methionine to the N7 position of the cap guanine. N7G-methyltransferase (MT) mediated reaction can be represented as: GpppN(pN)n + S-adenosylmethionine (Adomet) ->m7GpppN(pN)n + S-adenosylhomocysteine (Adohcy).

UnificationXref997
type: UnificationXref
id: REACT_27694
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27694.1

Evidence540
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: GMP capped mRNA transcript dissociates from GT for further modification.

UnificationXref994
type: UnificationXref
id: 981780
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=981780

UnificationXref995
type: UnificationXref
id: REACT_27567
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27567.2

SequenceSite897
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite898
type: SequenceSite
position status: EQUAL
sequence position: 1506

SequenceSite895
type: SequenceSite
position status: EQUAL
sequence position: 1507

SequenceSite896
type: SequenceSite
position status: EQUAL
sequence position: 1535

METAP1/2
type: Complex
data source: Provenance1
member physical entity: METAP1:2Co2+ (name copied from entity in Homo sapiens)
member physical entity: METAP2:2Co2+ (name copied from entity in Homo sapiens)
xref: UnificationXref3279
cellular location: GO_0005829
comment: Reactome DB_ID: 5617127
comment: Converted from EntitySet in Reactome

METAP1:2Co2+ (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry791
component stoichiometry: Stoichiometry792
component: SmallMolecule125
component: Protein1002
xref: UnificationXref3275
cellular location: GO_0005829
comment: Reactome DB_ID: 5617121

METAP2:2Co2+ (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry793
component stoichiometry: Stoichiometry794
component: SmallMolecule125
component: Protein1003
xref: UnificationXref3278
cellular location: GO_0005829
comment: Reactome DB_ID: 5617126

http://identifiers.org/pubmed/3129195
type: PublicationXref
id: 3129195
author: Baeuerle, PA
author: Baltimore, D
db: Pubmed
title: Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor
source: Cell 53:211-7
year: 1988

SequenceSite899
type: SequenceSite
position status: EQUAL
sequence position: 1536

DSIF complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry795
component stoichiometry: Stoichiometry796
component: Protein1009
component: Protein1008
xref: UnificationXref3310
cellular location: GO_0005654
comment: Reactome DB_ID: 5611210

FACT complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry797
component stoichiometry: Stoichiometry798
component: Protein1010
component: Protein1011
xref: UnificationXref3317
cellular location: GO_0005654
comment: Reactome DB_ID: 5611204

UnificationXref11070
type: UnificationXref
id: 159362
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159362

pol II open pre-initiation complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry823
component stoichiometry: Stoichiometry844
component stoichiometry: Stoichiometry831
component stoichiometry: Stoichiometry801
component stoichiometry: Stoichiometry819
component stoichiometry: Stoichiometry802
component stoichiometry: Stoichiometry845
component: TFIIA (name copied from entity in Homo sapiens)
component: TFIIH (name copied from entity in Homo sapiens)
component: PhysicalEntity75
component: TFIID (name copied from entity in Homo sapiens)
component: Protein1047
component: TFIIE (name copied from entity in Homo sapiens)
component: RNA Polymerase II (unphosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
xref: UnificationXref3397
cellular location: GO_0005654
comment: Reactome DB_ID: 5610538

SequenceSite890
type: SequenceSite
position status: EQUAL
sequence position: 398

TFIIE (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry799
component stoichiometry: Stoichiometry800
component: PhysicalEntity28
component: Protein1012
xref: UnificationXref3322
cellular location: GO_0005654
comment: Reactome DB_ID: 5610239

UnificationXref11072
type: UnificationXref
id: CHEBI:28790
db: ChEBI

RNA Polymerase II (unphosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry815
component stoichiometry: Stoichiometry818
component: RNA Polymerase II holoenzyme complex (unphosphorylated) (name copied from entity in Homo sapiens)
component: TFIIF (name copied from entity in Homo sapiens)
xref: UnificationXref3351
cellular location: GO_0005654
comment: Reactome DB_ID: 5609151

UnificationXref3638
type: UnificationXref
id: 111344
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111344

UnificationXref11071
type: UnificationXref
id: REACT_7869
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_7869.2

RNA Polymerase II holoenzyme complex (unphosphorylated) (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry814
component stoichiometry: Stoichiometry805
component stoichiometry: Stoichiometry806
component stoichiometry: Stoichiometry812
component stoichiometry: Stoichiometry807
component stoichiometry: Stoichiometry813
component stoichiometry: Stoichiometry808
component stoichiometry: Stoichiometry803
component stoichiometry: Stoichiometry804
component stoichiometry: Stoichiometry811
component stoichiometry: Stoichiometry809
component stoichiometry: Stoichiometry810
component: Protein1022
component: Protein1023
component: Protein1020
component: Protein1021
component: PhysicalEntity28
component: Protein1014
component: Protein1013
component: Protein1016
component: Protein1015
component: Protein1018
component: Protein1017
component: Protein1019
xref: UnificationXref3347
cellular location: GO_0005654
comment: Reactome DB_ID: 5609150

UnificationXref3639
type: UnificationXref
id: REACT_5463
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5463.1

SequenceSite893
type: SequenceSite
position status: EQUAL
sequence position: 1

TFIIF (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry816
component stoichiometry: Stoichiometry817
component: PhysicalEntity28
component: Protein1024
xref: UnificationXref3350
cellular location: GO_0005654
comment: Reactome DB_ID: 5609145

UnificationXref3636
type: UnificationXref
id: 5610677
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610677

SequenceSite894
type: SequenceSite
position status: EQUAL
sequence position: 2120

UnificationXref3637
type: UnificationXref
id: REACT_223050
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_223050.2

SequenceSite891
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref3634
type: UnificationXref
id: 111349
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111349

SequenceSite892
type: SequenceSite
position status: EQUAL
sequence position: 398

UnificationXref3635
type: UnificationXref
id: REACT_4307
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4307.1

UnificationXref11057
type: UnificationXref
id: 727787
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=727787

UnificationXref3620
type: UnificationXref
id: 72084
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72084

Evidence554
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9421509
comment: NARS (cytosolic asparaginyl tRNA synthetase) catalyzes the reaction of asparagine, tRNA(Asn), and ATP to form Asn-tRNA(Asn), AMP, and pyrophosphate. The enzyme is a class I tRNA synthetase (Beaulande et al. 1998).

UnificationXref11058
type: UnificationXref
id: REACT_22831
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_22831.2

UnificationXref980
type: UnificationXref
id: REACT_5808
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5808.1

Evidence553
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/7654687
xref: http://identifiers.org/pubmed/16906134
comment: AARS (cytosolic alanyl tRNA synthetase) catalyzes the reaction of alanine, tRNA(ala), and ATP to form Ala tRNA(Ala), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a monomer (Shiba et al. 1995). A mutation in the editing domain of the mouse Aars gene results in misincorporation of non-cognate amino acids into cellular proteins. This is associated with protein misfolding in Purkinje cells and a phenotype consistent with human ataxia (Lee et al. 2006).

UnificationXref11055
type: UnificationXref
id: 727735
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=727735

UnificationXref981
type: UnificationXref
id: 111940
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111940

UnificationXref3622
type: UnificationXref
id: 5610669
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610669

Evidence556
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12690580
comment: GARS (cytosolic glycyl tRNA synthetase) catalyzes the reaction of glycine, tRNA(Gly), and ATP to form Gly tRNA(Gly), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a dimer. Cytosolic and mitochondrial glycyl tRNA synthetase enzymes are both encoded by the same gene; the cytosolic protein lacks an aminoterminal 54 residue sequence found in the mitochondrial protein. Mutations in GARS are associated with Charcot Marie Tooth disease and distal spinal muscular atrophy, two diseases characterized by axonal dysfunction (Antonellis et al. 2006)

UnificationXref11056
type: UnificationXref
id: REACT_23033
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_23033.2

UnificationXref982
type: UnificationXref
id: REACT_5203
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5203.2

UnificationXref3621
type: UnificationXref
id: REACT_5393
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5393.1

Evidence555
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11347887
comment: CARS (cytosolic cysteinyl tRNA synthetase) catalyzes the reaction of cysteine, tRNA(cys), and ATP to form Cys-tRNA(Cys), AMP, and pyrophosphate. The enzyme, a class I tRNA synthetase, is a homomultimer, probably a dimer (Davidson et al. 2001).

UnificationXref11053
type: UnificationXref
id: 727739
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=727739

Evidence558
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11858721
comment: FARS (cytosolic phenylalanyl tRNA synthetase) catalyzes the reaction of phenylalanine, tRNA(Phe), and ATP to form Phe-tRNA(Phe), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a heterotetramer of two alpha and two beta subunits (Moor et al. 2002).

UnificationXref11054
type: UnificationXref
id: REACT_23094
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_23094.2

Evidence557
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11829477
comment: HARS (cytosolic histidyl tRNA synthetase) catalyzes the reaction of histidine, tRNA(His), and ATP to form His-tRNA(His), AMP, and pyrophosphate (Lee et al. 2002).

UnificationXref11051
type: UnificationXref
id: 727743
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=727743

UnificationXref11052
type: UnificationXref
id: REACT_22546
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_22546.2

Evidence559
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/7540217
xref: http://identifiers.org/pubmed/9431993
comment: SARS (cytosolic seryl tRNA synthetase) catalyzes the reaction of serine, tRNA(Ser), and ATP to form Ser-tRNA(Ser), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a homodimer (Hartlein and Cusack 1995; Vincent et al. 1997).

UnificationXref987
type: UnificationXref
id: 75165
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=75165

UnificationXref988
type: UnificationXref
id: REACT_5340
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5340.1

UnificationXref989
type: UnificationXref
id: P23179
db: UniProt

UnificationXref983
type: UnificationXref
id: 112453
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112453

Evidence550
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10207048
xref: http://identifiers.org/pubmed/9149533
comment: The splicing of a subset of pre-mRNA introns occurs by a second pathway, designated the AT-AC or U12-dependent splicing pathway. AT-AC introns have highly conserved, non-canonical splice sites that are removed by the AT-AC spliceosome, which contains distinct snRNAs (U11, U12, U4atac, U6atac) that are structurally and functionally analogous to the major spliceosome. U5 snRNA as well as many of the protein factors appear to be conserved between the two spliceosomes.

UnificationXref984
type: UnificationXref
id: REACT_4509
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4509.1

UnificationXref11059
type: UnificationXref
id: 727751
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=727751

UnificationXref985
type: UnificationXref
id: 111849
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111849

Evidence552
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Co-transcriptional pre-mRNA splicing is not obligatory. Pre-mRNA splicing begins co-transcriptionally and often continues post-transcriptionally. Human genes contain an average of nine introns per gene, which cannot serve as splicing substrates until both 5' and 3' ends of each intron are synthesized. Thus the time that it takes for pol II to synthesize each intron defines a minimal time and distance along the gene in which splicing factors can be recruited. The time that it takes for pol II to reach the end of the gene defines the maximal time in which splicing could occur co-transcriptionally. Thus, the kinetics of transcription can affect the kinetics of splicing.Any covalent change in a primary (nascent) mRNA transcript is mRNA Processing. For successful gene expression, the primary mRNA transcript needs to be converted to a mature mRNA prior to its translation into polypeptide. Eucaryotic mRNAs undergo a series of complex processing reactions; these begin on nascent transcripts as soon as a few ribonucleotides have been synthesized during transcription by RNA Polymerase II, through the export of the mature mRNA to the cytoplasm, and culminate with mRNA turnover in the cytoplasm.

UnificationXref986
type: UnificationXref
id: REACT_1202
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_1202.2

Evidence551
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12226669
comment: The process in which excision of introns from the primary transcript of messenger RNA (mRNA) is followed by ligation of the two exon termini exposed by removal of each intron, is called mRNA splicing. Most of the mRNA is spliced by the major pathway, involving the U1, U2, U4, U5 and U6 snRNPs. A minor fraction, about 1 %, of the mRNAs are spliced via the U12 dependent pathway.

SequenceSite884
type: SequenceSite
position status: EQUAL
sequence position: 398

TFIIA (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry820
component stoichiometry: Stoichiometry822
component stoichiometry: Stoichiometry821
component: Protein1027
component: Protein1026
component: Protein1025
xref: UnificationXref3357
cellular location: GO_0005654
comment: Reactome DB_ID: 5610186

SequenceSite885
type: SequenceSite
position status: EQUAL
sequence position: 1

TFIIH (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry830
component stoichiometry: Stoichiometry824
component stoichiometry: Stoichiometry825
component stoichiometry: Stoichiometry826
component stoichiometry: Stoichiometry827
component stoichiometry: Stoichiometry828
component stoichiometry: Stoichiometry829
component: CAK (name copied from entity in Homo sapiens)
component: Protein1032
component: Protein1031
component: Protein1033
component: Protein1030
component: Protein1029
component: Protein1028
xref: UnificationXref3370
cellular location: GO_0005654
comment: Reactome DB_ID: 5610158

SequenceSite886
type: SequenceSite
position status: EQUAL
sequence position: 398

SequenceSite887
type: SequenceSite
position status: EQUAL
sequence position: 1

http://identifiers.org/pubmed/18772396
type: PublicationXref
id: 18772396
author: Zhang, X
author: Shinjo, SM
author: Rasheed, BA
author: Lin, JC
author: Carter, H
author: Jones, S
author: Keir, S
author: Parmigiani, G
author: Yan, H
author: McLendon, R
author: Olivi, A
author: Nikolsky, Y
author: Diaz Jr, LA
author: Tekleab, H
author: Vogelstein, B
author: Kinzler, KW
author: Velculescu, VE
author: Papadopoulos, N
author: Mankoo, P
author: Marie, SK
author: Parsons, DW
author: Busam, DA
author: Riggins, GJ
author: Bigner, DD
author: Karchin, R
author: Hartigan, J
author: Angenendt, P
author: Leary, RJ
author: Smith, DR
author: Strausberg, RL
author: Gallia, GL
author: Siu, IM
author: Nikolskaya, T
db: Pubmed
title: An integrated genomic analysis of human glioblastoma multiforme
source: Science 321:1807-12
year: 2008

SequenceSite888
type: SequenceSite
position status: EQUAL
sequence position: 398

pol II promoter:TFIID:TFIIA:TFIIB:Pol II:TFIIF complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry852
component stoichiometry: Stoichiometry853
component: pol II promoter:TFIID:TFIIA:TFIIB complex (name copied from entity in Homo sapiens)
component: RNA Polymerase II (unphosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
xref: UnificationXref3402
cellular location: GO_0005654
comment: Reactome DB_ID: 5610494

SequenceSite889
type: SequenceSite
position status: EQUAL
sequence position: 1

pol II promoter:TFIID:TFIIA:TFIIB complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry850
component stoichiometry: Stoichiometry851
component stoichiometry: Stoichiometry847
component: TFIIA (name copied from entity in Homo sapiens)
component: Protein1047
component: pol II promoter:TFIID complex (name copied from entity in Homo sapiens)
xref: UnificationXref3401
cellular location: GO_0005654
comment: Reactome DB_ID: 5610493

TFIID (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry843
component stoichiometry: Stoichiometry841
component stoichiometry: Stoichiometry832
component stoichiometry: Stoichiometry842
component stoichiometry: Stoichiometry833
component stoichiometry: Stoichiometry840
component stoichiometry: Stoichiometry839
component stoichiometry: Stoichiometry838
component stoichiometry: Stoichiometry835
component stoichiometry: Stoichiometry834
component stoichiometry: Stoichiometry837
component stoichiometry: Stoichiometry836
component: Protein1039
component: Protein1035
component: Protein1036
component: Protein1037
component: PhysicalEntity28
component: Protein1038
component: Protein1044
component: Protein1043
component: Protein1034
component: Protein1042
component: Protein1041
component: Protein1040
xref: UnificationXref3394
cellular location: GO_0005654
comment: Reactome DB_ID: 5610234

pol II closed pre-initiation complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry854
component stoichiometry: Stoichiometry855
component stoichiometry: Stoichiometry846
component: TFIIH (name copied from entity in Homo sapiens)
component: pol II promoter:TFIID:TFIIA:TFIIB:Pol II:TFIIF complex (name copied from entity in Homo sapiens)
component: TFIIE (name copied from entity in Homo sapiens)
xref: UnificationXref3403
cellular location: GO_0005654
comment: Reactome DB_ID: 5610542

UnificationXref11061
type: UnificationXref
id: 5615133
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615133

Pol II initiation complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry865
component stoichiometry: Stoichiometry866
component stoichiometry: Stoichiometry863
component stoichiometry: Stoichiometry864
component stoichiometry: Stoichiometry859
component stoichiometry: Stoichiometry867
component: TFIIA (name copied from entity in Homo sapiens)
component: TFIID (name copied from entity in Homo sapiens)
component: Protein1047
component: PhysicalEntity77
component: RNA Polymearse II:NTP:TFIIF complex (name copied from entity in Homo sapiens)
component: TFIIE (name copied from entity in Homo sapiens)
xref: UnificationXref3424
cellular location: GO_0005654
comment: Reactome DB_ID: 5610540

UnificationXref3627
type: UnificationXref
id: 5610671
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610671

http://identifiers.org/pubmed/17035995
type: PublicationXref
id: 17035995
author: De Camilli, Pietro
author: Di Paolo, G
db: Pubmed
title: Phosphoinositides in cell regulation and membrane dynamics
source: Nature 443:651-7
year: 2006

UnificationXref11060
type: UnificationXref
id: REACT_23315
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_23315.2

RNA Polymearse II:NTP:TFIIF complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry861
component stoichiometry: Stoichiometry862
component stoichiometry: Stoichiometry860
component: TFIIH (name copied from entity in Homo sapiens)
component: SmallMolecule55
component: RNA Polymerase II (unphosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
xref: UnificationXref3421
cellular location: GO_0005654
comment: Reactome DB_ID: 5610539

UnificationXref3628
type: UnificationXref
id: 5610673
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610673

pol II promoter:TFIID complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry849
component stoichiometry: Stoichiometry848
component: PhysicalEntity76
component: TFIID (name copied from entity in Homo sapiens)
xref: UnificationXref3400
cellular location: GO_0005654
comment: Reactome DB_ID: 5610492

UnificationXref3629
type: UnificationXref
id: REACT_219305
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_219305.2

pol II promoter:TFIID:TFIIA:TFIIB:Pol II:TFIIF:TFIIE complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry857
component stoichiometry: Stoichiometry856
component: pol II promoter:TFIID:TFIIA:TFIIB:Pol II:TFIIF complex (name copied from entity in Homo sapiens)
component: TFIIE (name copied from entity in Homo sapiens)
xref: UnificationXref3414
cellular location: GO_0005654
comment: Reactome DB_ID: 5610787

SequenceSite880
type: SequenceSite
position status: EQUAL
sequence position: 433

UnificationXref3623
type: UnificationXref
id: 5610670
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610670

SequenceSite881
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref3624
type: UnificationXref
id: REACT_226461
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_226461.2

SequenceSite882
type: SequenceSite
position status: EQUAL
sequence position: 398

UnificationXref3625
type: UnificationXref
id: 111341
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111341

SequenceSite883
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref3626
type: UnificationXref
id: REACT_5790
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5790.1

UnificationXref11040
type: UnificationXref
id: 5610762
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610762

UnificationXref11041
type: UnificationXref
id: 5610765
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610765

UnificationXref11042
type: UnificationXref
id: REACT_221643
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_221643.2

Evidence569
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15779907
xref: http://identifiers.org/pubmed/17384640
comment: DARS2 (mitochondrial aspartyl tRNA synthetase) catalyzes the reaction of aspartate, mitochondrial tRNA(Asp), and ATP to form Asp tRNA(Asp), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a homodimer (Bonnefond et al. 2005). Homozygosity for DARS2 mutations is associated with leukoencephalopathy with brainstem and spinal cord involvement plus lactate elevation (Scheper et al 2007).

UnificationXref11043
type: UnificationXref
id: 5610774
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610774

Evidence568
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15779907
comment: NARS2 (mitochondrial asparaginyl tRNA synthetase) catalyzes the reaction of asparagine, mitochondrial tRNA(Asn), and ATP to form Asn-tRNA(Asn), AMP, and pyrophosphate. The NARS2 gene has been identified by computational analysis of the human genome sequence; its function has been inferred from those of the biochemically characterized mitochondrial aspartyl and tyrosyl tRNA synthetases (Bonnefond et al. 2005).

UnificationXref11044
type: UnificationXref
id: REACT_210185
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_210185.2

UnificationXref3611
type: UnificationXref
id: 2466323
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2466323

Evidence567
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17847012
comment: RARS2 (mitochondrial arginyl tRNA synthetase) catalyzes the reaction of arginine, mitochondrial tRNA(Arg), and ATP to form Arg tRNA(Arg), AMP, and pyrophosphate. The enzyme is a class I tRNA synthetase. Homozygosity for RARS2 mutations has been associated with pontocerebellar hypoplasia â a disease characterized by a severe reduction in cerebellum and brainstem size (Edvardson et al. 2007).

UnificationXref11045
type: UnificationXref
id: 5610764
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610764

UnificationXref3610
type: UnificationXref
id: P10566
db: UniProt

Evidence566
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15779907
comment: AARS2 (mitochondrial alanyl tRNA synthetase) catalyzes the reaction of alanine, mitochondrial tRNA(Ala), and ATP to form Ala-tRNA(Ala), AMP, and pyrophosphate. The AARS2 gene has been identified by computational analysis of the human genome sequence; its function has been inferred from those of the biochemically characterized mitochondrial aspartyl and tyrosyl tRNA synthetases (Bonnefond et al. 2005).

UnificationXref11046
type: UnificationXref
id: REACT_206348
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_206348.2

Evidence565
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16169847
xref: http://identifiers.org/pubmed/9878398
xref: http://identifiers.org/pubmed/14500886
comment: Cytosolic tRNA synthetases catalyze the reactions of tRNAs encoded in the nuclear genome, their cognate amino acids, and ATP to form aminoacyl-tRNAs, AMP, and pyrophosphate. Eight of the tRNA synthetases, those specific for arginine, aspartate, glutamate and proline, glutamine, isoleucine, leucine, lysine, and methionine, associate to form a complex with three accessory proteins. Each of the component synthetases is active in vitro as a purified protein; complex formation is thought to channel aminoacylated tRNAs more efficiently to the site of protein synthesis in mRNA:ribosome complexes (Quevillon et al. 1999; Wolfe et al. 2003, 2005).

UnificationXref11047
type: UnificationXref
id: 727755
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=727755

Evidence564
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/656444
xref: http://identifiers.org/pubmed/4130389
xref: http://identifiers.org/pubmed/6022858
comment: Cytosolic PPA1 (pyrophosphatase (inorganic) 1) catalyzes the hydrolysis of pyrophosphate to yield two molecules of orthophosphate. The enzyme, a homodimer, requires Mg++ for activity (Fisher et al. 1974; Pynes and Younathan 1967; Thuiller et al. 1978).

UnificationXref11048
type: UnificationXref
id: REACT_22579
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_22579.2

Evidence563
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8428657
comment: VARS (cytosolic valyl tRNA synthetase) catalyzes the reaction of valine, tRNA(Val), and ATP to form Val-tRNA(Val), AMP, and pyrophosphate. The enzyme is a class I tRNA synthetase (Vilalta et al. 1993).

UnificationXref11049
type: UnificationXref
id: 727758
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=727758

Evidence562
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16429158
xref: http://identifiers.org/pubmed/14671330
comment: YARS (cytosolic tyrosyl tRNA synthetase) catalyzes the reaction of tyrosine, tRNA(Tyr), and ATP to form Tyr tRNA(Tyr), AMP, and pyrophosphate. The enzyme, a class I tRNA synthetase, is a homodimer (Yang et al. 2003). Mutations in the YARS gene are associated with dominant-intermediate Charcot-Marie-Tooth disease â a form of peripheral neuropathy characterized by axon and Schwann cell dysfunction (Jordanova et al. 2006).

Evidence561
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/1373391
xref: http://identifiers.org/pubmed/14660560
xref: http://identifiers.org/pubmed/1761529
comment: WARS (cytosolic tryptophanyl tRNA synthetase) catalyzes the reaction of tryptophan, tRNA(Trp), and ATP to form Trp-tRNA(Trp), AMP, and pyrophosphate. The enzyme, a class I tRNA synthetase, is a homodimer (Bange et al. 1992; Rubin et al. 1991; Yu et al. 2004).

Evidence560
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/7118399
comment: TARS (cytosolic threonyl tRNA synthetase) catalyzes the reaction of threonine, tRNA(Thr), and ATP to form Thr-tRNA(Thr), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a homodimer (Pan et al. 1982).

http://identifiers.org/pubmed/8565070
type: PublicationXref
id: 8565070
author: Sentenac, A
author: Dieci, G
db: Pubmed
title: Facilitated recycling pathway for RNA polymerase III.
source: Cell 84:245-52
year: 1996

Activation of NF-kappaB in B cells
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction146
evidence: Evidence277
xref: UnificationXref2250
xref: UnificationXref2249
pathway order: PathwayStep270
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

SequenceSite879
type: SequenceSite
position status: EQUAL
sequence position: 1

pol II transcription complex containing 4 nucleotide long transcript (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry891
component stoichiometry: Stoichiometry889
component stoichiometry: Stoichiometry890
component stoichiometry: Stoichiometry893
component stoichiometry: Stoichiometry892
component stoichiometry: Stoichiometry894
component: TFIIA (name copied from entity in Homo sapiens)
component: TFIIH (name copied from entity in Homo sapiens)
component: TFIID (name copied from entity in Homo sapiens)
component: PhysicalEntity81
component: TFIIE (name copied from entity in Homo sapiens)
component: RNA Polymerase II (unphosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
xref: UnificationXref3448
cellular location: GO_0005654
comment: Reactome DB_ID: 5610547

pol II transcription complex containing 9 nucleotide long transcript (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry897
component stoichiometry: Stoichiometry896
component stoichiometry: Stoichiometry898
component: TFIIH (name copied from entity in Homo sapiens)
component: PhysicalEntity82
component: RNA Polymerase II (unphosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
xref: UnificationXref3453
cellular location: GO_0005654
comment: Reactome DB_ID: 5610549

SequenceSite877
type: SequenceSite
position status: EQUAL
sequence position: 1

pol II transcription complex containing 11 nucleotide long transcript (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry901
component stoichiometry: Stoichiometry900
component stoichiometry: Stoichiometry902
component: TFIIH (name copied from entity in Homo sapiens)
component: PhysicalEntity83
component: RNA Polymerase II (unphosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
xref: UnificationXref3456
cellular location: GO_0005654
comment: Reactome DB_ID: 5610620

SequenceSite878
type: SequenceSite
position status: EQUAL
sequence position: 433

Pol II transcription complex containing extruded transcript to +30 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry903
component stoichiometry: Stoichiometry905
component stoichiometry: Stoichiometry904
component: TFIIH (name copied from entity in Homo sapiens)
component: PhysicalEntity84
component: RNA Polymerase II (unphosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
xref: UnificationXref3461
cellular location: GO_0005654
comment: Reactome DB_ID: 5610655

SequenceSite875
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite876
type: SequenceSite
position status: EQUAL
sequence position: 433

Pol II Initiation complex with phosphodiester-PPi intermediate (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry874
component stoichiometry: Stoichiometry869
component stoichiometry: Stoichiometry868
component stoichiometry: Stoichiometry871
component stoichiometry: Stoichiometry870
component stoichiometry: Stoichiometry873
component stoichiometry: Stoichiometry872
component: TFIIA (name copied from entity in Homo sapiens)
component: TFIIH (name copied from entity in Homo sapiens)
component: TFIID (name copied from entity in Homo sapiens)
component: PhysicalEntity78
component: Protein1047
component: TFIIE (name copied from entity in Homo sapiens)
component: RNA Polymerase II (unphosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
xref: UnificationXref3429
cellular location: GO_0005654
comment: Reactome DB_ID: 5610544

SequenceSite873
type: SequenceSite
position status: EQUAL
sequence position: 1

pol II transcription complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry880
component stoichiometry: Stoichiometry878
component stoichiometry: Stoichiometry879
component stoichiometry: Stoichiometry875
component stoichiometry: Stoichiometry877
component stoichiometry: Stoichiometry876
component stoichiometry: Stoichiometry881
component: TFIIA (name copied from entity in Homo sapiens)
component: TFIIH (name copied from entity in Homo sapiens)
component: TFIID (name copied from entity in Homo sapiens)
component: Protein1047
component: PhysicalEntity79
component: TFIIE (name copied from entity in Homo sapiens)
component: RNA Polymerase II (unphosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
xref: UnificationXref3436
cellular location: GO_0005654
comment: Reactome DB_ID: 5610240

SequenceSite874
type: SequenceSite
position status: EQUAL
sequence position: 433

pol II transcription complex containing 3 Nucleotide long transcript (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry888
component stoichiometry: Stoichiometry887
component stoichiometry: Stoichiometry886
component stoichiometry: Stoichiometry885
component stoichiometry: Stoichiometry884
component stoichiometry: Stoichiometry883
component stoichiometry: Stoichiometry882
component: TFIIA (name copied from entity in Homo sapiens)
component: TFIIH (name copied from entity in Homo sapiens)
component: TFIID (name copied from entity in Homo sapiens)
component: Protein1047
component: PhysicalEntity80
component: TFIIE (name copied from entity in Homo sapiens)
component: RNA Polymerase II (unphosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
xref: UnificationXref3443
cellular location: GO_0005654
comment: Reactome DB_ID: 5610519

SequenceSite871
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref3614
type: UnificationXref
id: 2466294
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2466294

SequenceSite872
type: SequenceSite
position status: EQUAL
sequence position: 433

UnificationXref3615
type: UnificationXref
id: REACT_164897
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_164897.1

UnificationXref3612
type: UnificationXref
id: REACT_164290
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_164290.1

SequenceSite870
type: SequenceSite
position status: EQUAL
sequence position: 433

UnificationXref3613
type: UnificationXref
id: P23500
db: UniProt

Pol II transcription complex with (ser5) phosphorylated CTD containing extruded transcript to +30 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry907
component stoichiometry: Stoichiometry906
component stoichiometry: Stoichiometry922
component: TFIIH (name copied from entity in Homo sapiens)
component: PhysicalEntity84
component: RNA polymerase II (phosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
xref: UnificationXref3473
cellular location: GO_0005654
comment: Reactome DB_ID: 5610653

UnificationXref3618
type: UnificationXref
id: 2466303
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2466303

RNA polymerase II (phosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry921
component stoichiometry: Stoichiometry920
component: TFIIF (name copied from entity in Homo sapiens)
component: RNA Polymerase II holoenzyme complex (phosphorylated) (name copied from entity in Homo sapiens)
xref: UnificationXref3472
cellular location: GO_0005654
comment: Reactome DB_ID: 5609146

UnificationXref3619
type: UnificationXref
id: REACT_163940
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_163940.2

UnificationXref11050
type: UnificationXref
id: REACT_23113
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_23113.2

RNA Polymerase II holoenzyme complex (phosphorylated) (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry910
component stoichiometry: Stoichiometry919
component stoichiometry: Stoichiometry917
component stoichiometry: Stoichiometry909
component stoichiometry: Stoichiometry918
component stoichiometry: Stoichiometry908
component stoichiometry: Stoichiometry915
component stoichiometry: Stoichiometry916
component stoichiometry: Stoichiometry913
component stoichiometry: Stoichiometry914
component stoichiometry: Stoichiometry911
component stoichiometry: Stoichiometry912
component: Protein1048
component: Protein1023
component: Protein1020
component: Protein1021
component: PhysicalEntity28
component: Protein1014
component: Protein1013
component: Protein1016
component: Protein1015
component: Protein1018
component: Protein1017
component: Protein1019
xref: UnificationXref3471
cellular location: GO_0005654
comment: Reactome DB_ID: 5609140

UnificationXref3616
type: UnificationXref
id: 2466280
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2466280

UnificationXref3617
type: UnificationXref
id: REACT_164236
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_164236.2

http://identifiers.org/pubmed/2040271
type: PublicationXref
id: 2040271
author: Sadahiro, S
author: Matsuda, T
author: Takenaka, M
author: Tanaka, T
author: Noguchi, T
author: Hirai, H
author: Imai, E
author: Yamada, K
db: Pubmed
title: Isolation and characterization of the human pyruvate kinase M gene
source: Eur J Biochem 198:101-6
year: 1991

UnificationXref11031
type: UnificationXref
id: REACT_4158
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4158.2

UnificationXref11032
type: UnificationXref
id: 83957
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=83957

Evidence579
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15779907
comment: PARS2 (mitochondrial prolyl tRNA synthetase) catalyzes the reaction of proline, mitochondrial tRNA(Pro), and ATP to form Pro-tRNA(Pro), AMP, and pyrophosphate. The PARS2 gene has been identified by computational analysis of the human genome sequence; its function has been inferred from those of the biochemically characterized mitochondrial aspartyl and tyrosyl tRNA synthetases (Bonnefond et al. 2005).

UnificationXref11030
type: UnificationXref
id: 83955
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=83955

UnificationXref11035
type: UnificationXref
id: REACT_4570
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4570.2

Evidence576
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9278442
comment: KARS (mitochondrial lysyl tRNA synthetase) catalyzes the reaction of lysine, tRNA(Lys), and ATP to form Lys-tRNA(Lys), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a homodimer. The same gene encodes both cytosolic and mitochondrial KARS enzymes (Shiba et al. 1997).

5,10-methylenetetrahydrofolate polyglutamate
type: SmallMoleculeReference
name: 5,10-methylenetetrahydrofolate polyglutamate macromolecule
name: 5,10-methylenetetrahydrofolate polyglutamate macromolecule [ChEBI:60473]
xref: UnificationXref6970

UnificationXref11036
type: UnificationXref
id: 83961
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=83961

Evidence575
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10684970
comment: LARS2 (mitochondrial leucyl tRNA synthetase) catalyzes the reaction of leucine, mitochondrial tRNA(Leu), and ATP to form Leu-tRNA(Leu), AMP, and pyrophosphate. The enzyme, a class I tRNA synthetase, is a monomer (Bullard et al. 2000).

UnificationXref11033
type: UnificationXref
id: REACT_3780
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3780.2

UnificationXref3600
type: UnificationXref
id: 5618687
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618687

Evidence578
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10329163
comment: FARS2 (mitochondrial phenylalanyl tRNA synthetase) catalyzes the reaction of phenylalanine, mitochondrial tRNA(Phe), and ATP to form Phe-tRNA(Phe), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a monomer (Bullard et al. 1999).

UnificationXref11034
type: UnificationXref
id: 83959
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=83959

Evidence577
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15274629
comment: MARS2 (mitochondrial methionyl tRNA synthetase) catalyzes the reaction of methionine, mitochondrial tRNA(Met), and ATP to form Met-tRNA(Met), AMP, and pyrophosphate. The enzyme, a class I tRNA synthetase, is a monomer (Spencer et al. 2004).

UnificationXref11039
type: UnificationXref
id: 5610761
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610761

Evidence572
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12690580
comment: GARS (mitochondrial glycyl tRNA synthetase) catalyzes the reaction of glycine, tRNA(Gly), and ATP to form Gly-tRNA(Gly), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a dimer. Cytosolic and mitochondrial glycyl tRNA synthetase enzymes are both encoded by the same gene; the cytosolic protein lacks an aminoterminal 54-residue sequence found in the mitochondrial protein. Mutations in GARS are associated with Charcot-Marie-Tooth disease (Antonellis et al. 2007).

Evidence571
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8078941
comment: QARS (mitochondrial glutaminyl tRNA synthetase) catalyzes the reaction of glutamine, tRNA(Gln), and ATP to form Gln-tRNA(Gln), AMP, and pyrophosphate. The enzyme is a class I tRNA synthetase. The same gene encodes both the cytosolic and mitochondrial QARS enzymes (Lamour et al. 1994).

UnificationXref11037
type: UnificationXref
id: REACT_2968
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2968.2

Evidence574
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9466989
comment: IARS2 (mitochondrial isoleucyl tRNA synthetase) catalyzes the reaction of isoleucine, mitochondrial tRNA(Ile), and ATP to form Ile-tRNA(Ile), AMP, and pyrophosphate. The enzyme is a class I tRNA synthetase (Degoul et al. 1995).

UnificationXref11038
type: UnificationXref
id: 5610756
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610756

Evidence573
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/7755634
comment: HARS2 (mitochondrial histidyl tRNA synthetase) catalyzes the reaction of histidine, mitochondrial tRNA(His), and ATP to form His-tRNA(His), AMP, and pyrophosphate. The enzyme is a class II tRNA synthetase (O'Hanlon et al. 1995).

SequenceSite859
type: SequenceSite
position status: EQUAL
sequence position: 1384

Evidence570
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15779907
comment: EARS2 (mitochondrial glutamyl tRNA synthetase) catalyzes the reaction of glutamate, mitochondrial tRNA(Glu), and ATP to form Glu-tRNA(Glu), AMP, and pyrophosphate. The EARS2 gene has been identified by computational analysis of the human genome sequence; its function has been inferred from those of the biochemically characterized mitochondrial aspartyl and tyrosyl tRNA synthetases (Bonnefond et al. 2005).

SequenceSite866
type: SequenceSite
position status: EQUAL
sequence position: 332

RNA Polymerase II holoenzyme complex (hypophosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry941
component stoichiometry: Stoichiometry940
component stoichiometry: Stoichiometry943
component stoichiometry: Stoichiometry942
component stoichiometry: Stoichiometry944
component stoichiometry: Stoichiometry951
component stoichiometry: Stoichiometry945
component stoichiometry: Stoichiometry946
component stoichiometry: Stoichiometry947
component stoichiometry: Stoichiometry939
component stoichiometry: Stoichiometry948
component stoichiometry: Stoichiometry949
component stoichiometry: Stoichiometry950
component: Protein1048
component: PhysicalEntity28
component: Protein1014
component: Protein1013
component: Protein1016
component: Protein1015
component: Protein1018
component: Protein1017
component: Protein1019
component: Protein1023
component: Protein1020
component: Protein1021
component: TFIIF (name copied from entity in Homo sapiens)
xref: UnificationXref3497
cellular location: GO_0005654
comment: Reactome DB_ID: 5611192

UnificationXref3609
type: UnificationXref
id: REACT_4623
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4623.2

SequenceSite867
type: SequenceSite
position status: EQUAL
sequence position: 1

RNA Pol II (hypophosphorylated) complex bound to DSIF protein (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry956
component stoichiometry: Stoichiometry957
component: RNA Pol II (hypophosphorylated):capped pre-mRNA complex (name copied from entity in Homo sapiens)
component: DSIF complex (name copied from entity in Homo sapiens)
xref: UnificationXref3501
cellular location: GO_0005654
comment: Reactome DB_ID: 5611216

SequenceSite868
type: SequenceSite
position status: EQUAL
sequence position: 1015

RNA Polymerase II (phosphorylated):TFIIF:capped pre-mRNA (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry936
component stoichiometry: Stoichiometry937
component: PhysicalEntity85
component: RNA polymerase II (phosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
xref: UnificationXref3495
cellular location: GO_0005654
comment: Reactome DB_ID: 5609147

SequenceSite869
type: SequenceSite
position status: EQUAL
sequence position: 1

RNA Pol II (hypophosphorylated):capped pre-mRNA complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry955
component stoichiometry: Stoichiometry952
component stoichiometry: Stoichiometry953
component stoichiometry: Stoichiometry954
component: RNA Polymerase II holoenzyme complex (hypophosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
component: PhysicalEntity85
component: Cap Binding Complex (CBC) (name copied from entity in Homo sapiens)
component: Protein1051
xref: UnificationXref3498
cellular location: GO_0005654
comment: Reactome DB_ID: 5611193

SequenceSite862
type: SequenceSite
position status: EQUAL
sequence position: 1401

capped pre-mRNA:CBC:RNA Pol II (phosphorylated) complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry935
component stoichiometry: Stoichiometry938
component: RNA Polymerase II (phosphorylated):TFIIF:capped pre-mRNA (name copied from entity in Homo sapiens)
component: Cap Binding Complex (CBC) (name copied from entity in Homo sapiens)
xref: UnificationXref3496
cellular location: GO_0005654
comment: Reactome DB_ID: 5609148

SequenceSite863
type: SequenceSite
position status: EQUAL
sequence position: 1

Cap Binding Complex (CBC) (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry933
component stoichiometry: Stoichiometry934
component: Protein678
component: Protein677
xref: UnificationXref3492
cellular location: GO_0005654
comment: Reactome DB_ID: 5609094

SequenceSite864
type: SequenceSite
position status: EQUAL
sequence position: 741

RNA Pol II with phosphorylated CTD: CE complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry926
component stoichiometry: Stoichiometry923
component stoichiometry: Stoichiometry924
component stoichiometry: Stoichiometry925
component: TFIIH (name copied from entity in Homo sapiens)
component: Protein1049
component: PhysicalEntity84
component: RNA polymerase II (phosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
xref: UnificationXref3478
cellular location: GO_0005654
comment: Reactome DB_ID: 5610651

SequenceSite865
type: SequenceSite
position status: EQUAL
sequence position: 308

CE:Pol II CTD:Spt5 complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry932
component stoichiometry: Stoichiometry931
component stoichiometry: Stoichiometry930
component stoichiometry: Stoichiometry927
component stoichiometry: Stoichiometry928
component stoichiometry: Stoichiometry929
component: TFIIH (name copied from entity in Homo sapiens)
component: Protein1049
component: PhysicalEntity84
component: Protein1009
component: Protein1050
component: RNA polymerase II (phosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
xref: UnificationXref3485
cellular location: GO_0005654
comment: Reactome DB_ID: 5610667

UnificationXref3601
type: UnificationXref
id: REACT_261335
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_261335.1

UnificationXref3602
type: UnificationXref
id: 5618682
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618682

SequenceSite860
type: SequenceSite
position status: EQUAL
sequence position: 1389

UnificationXref3603
type: UnificationXref
id: REACT_237484
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_237484.1

SequenceSite861
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref3604
type: UnificationXref
id: 5618683
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618683

UnificationXref3605
type: UnificationXref
id: REACT_243664
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_243664.1

UnificationXref3606
type: UnificationXref
id: 1362385
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1362385

RBBP7:Replicative histone H3 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry959
component stoichiometry: Stoichiometry958
component: Protein1095
component: Protein1094
xref: UnificationXref3593
cellular location: GO_0005654
comment: Reactome DB_ID: 5617907

UnificationXref3607
type: UnificationXref
id: REACT_151452
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_151452.1

UnificationXref3608
type: UnificationXref
id: 113531
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113531

Capping complex (initial) (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry962
component stoichiometry: Stoichiometry960
component stoichiometry: Stoichiometry961
component: PhysicalEntity88
component: CE:Pol II CTD:Spt5 complex (name copied from entity in Homo sapiens)
component: PhysicalEntity5
xref: UnificationXref3622
cellular location: GO_0005654
comment: Reactome DB_ID: 5610669

UnificationXref11027
type: UnificationXref
id: REACT_2296
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2296.2

UnificationXref11026
type: UnificationXref
id: 83947
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=83947

UnificationXref11029
type: UnificationXref
id: REACT_5362
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5362.2

UnificationXref11028
type: UnificationXref
id: 83918
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=83918

Capping complex (hydrolyzed) (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry964
component stoichiometry: Stoichiometry965
component stoichiometry: Stoichiometry963
component: PhysicalEntity89
component: CE:Pol II CTD:Spt5 complex (name copied from entity in Homo sapiens)
component: PhysicalEntity5
xref: UnificationXref3627
cellular location: GO_0005654
comment: Reactome DB_ID: 5610671

UnificationXref11023
type: UnificationXref
id: 83924
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=83924

Evidence500
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8946909
comment: The general transcription factor TFIIF has a high affinity for the RNA Polymerase II holoenzyme. TFIIF stabilizes the preinitiation complex, and suppresses non-specific binding of RNA Pol II to DNA, and is thus critical for start site recognition.

UnificationXref3676
type: UnificationXref
id: P43321
db: UniProt

UnificationXref11022
type: UnificationXref
id: CHEBI:16040
db: ChEBI

Evidence501
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8946909
comment: The binding of TFIIH completes the assembly of the preinitiation complex (PIC) for RNA Polymerase II transcription. Although RNA polymerase binds the TATA box on the promoter DNA, no initiation of transcription occurs until TFIIH is bound to the PIC. TFIIH is the only factor with known enzymatic activities.

UnificationXref3677
type: UnificationXref
id: 5610422
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610422

UnificationXref11025
type: UnificationXref
id: 5610757
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610757

UnificationXref3674
type: UnificationXref
id: MOD:00599
db: MOD

UnificationXref11024
type: UnificationXref
id: REACT_3746
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3746.2

UnificationXref3675
type: UnificationXref
id: 5610412
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610412

Evidence504
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: At the beginning of this reaction, 1 molecule of 'pol II open pre-initiation complex', and 2 molecules of 'NTP' are present. At the end of this reaction, 1 molecule of 'Pol II initiation complex' is present. This reaction takes place in the 'nucleus'.

UnificationXref3672
type: UnificationXref
id: REACT_4280
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4280.1

http://identifiers.org/pubmed/3356695
type: PublicationXref
id: 3356695
author: Panniers, R
author: Rowlands, AG
author: Henshaw, EC
db: Pubmed
title: The catalytic mechanism of guanine nucleotide exchange factor action and competitive inhibition by phosphorylated eukaryotic initiation factor 2.
source: J Biol Chem 263:5526-33
year: 1988

UnificationXref1530
type: UnificationXref
id: 5607947
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607947

Evidence505
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: At the beginning of this reaction, 1 molecule of 'Pol II initiation complex' is present. At the end of this reaction, 1 molecule of 'Pol II Initiation complex with phosphodiester-PPi intermediate' is present. This reaction takes place in the 'nucleus'.

UnificationXref3673
type: UnificationXref
id: P40018
db: UniProt

UnificationXref11021
type: UnificationXref
id: REACT_224735
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_224735.2

UnificationXref1531
type: UnificationXref
id: 5607948
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607948

Evidence502
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8946909
comment: Formation of the pre-initiation complex

UnificationXref3670
type: UnificationXref
id: REACT_258595
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_258595.1

UnificationXref11020
type: UnificationXref
id: 5610773
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610773

UnificationXref1532
type: UnificationXref
id: REACT_106300
db: Reactome
id version: 4
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_106300.4

Evidence503
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/1310361
xref: http://identifiers.org/pubmed/7151173
xref: http://identifiers.org/pubmed/10024882
xref: http://identifiers.org/pubmed/10723029
xref: http://identifiers.org/pubmed/8490964
xref: http://identifiers.org/pubmed/8156590
xref: http://identifiers.org/pubmed/9405375
xref: http://identifiers.org/pubmed/8946909
comment: After assembly of the complete RNA polymerase II-preinitiation complex, the next step is separation of the two DNA strands. This isomerization step is known as the closed-to-open complex transition and occurs prior to the initiation of mRNA synthesis. In the RNA polymerase II system this step requires the hydrolysis of ATP or dATP into Pi and ADP or dADP (in contrast to the other RNA polymerase systems) and is catalyzed by the XPB subunit of TFIIH. The region of the promoter, which becomes single-stranded , spans from ââ¬â10 to +2 relative to the transcription start site. Negative supercoiling in the promoter region probably induces transient opening events and can alleviate requirement of TFIIE, TFIIH and ATP-hydrolysis for open complex formation. ATP is also used in this step by the cdk7-subunit of TFIIH to phosphorylate the heptad repeats of the C-terminal domain of the largest subunit of RNA polymerase II (RPB1) on serine-2

UnificationXref3671
type: UnificationXref
id: 77466
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=77466

UnificationXref1534
type: UnificationXref
id: 5607964
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607964

Evidence509
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11784853
xref: http://identifiers.org/pubmed/9405375
comment: Formation of the third phosphodiester bond creates a 4-nt product. This commits the initiation complex to promoter escape. The short 4-nt transcript is still loosely associated with the RNA polymerase II initiation complex and can dissociate to yield abortive products, which are not further extended. Inhibition of ATP-hydrolysis by TFIIH does not lead to collapse of the open region any longer. The transcription complex has lost the sensitivity to single-stranded oligo-nucleotide inhibition. However, ATP-hydrolysis and TFIIH are required for efficient promoter escape. The open region (ââ¬Åtranscription bubbleââ¬Â) expands concomitant with the site of RNA-extension. In this case this region spans positions -9 to +4.

UnificationXref1533
type: UnificationXref
id: 5607963
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607963

Evidence508
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11784853
xref: http://identifiers.org/pubmed/9405375
comment: Formation of the second phosphodiester bond creates a 3-nt product. This short transcript is still loosely associated with the RNA polymerase II initiation complex and can dissociate to yield abortive products, which are not further extended. The transcription complex still requires continued ATP-hydrolysis by TFIIH and remains sensitive to single-stranded oligo-nucleotide inhibition. The open region (ââ¬Åtranscription bubbleââ¬Â) expands concomitant with the site of RNA-extension. In this case this region spans positions -9 to +3.

U4 ATAC snRNP:U6 ATAC snRNP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry996
component stoichiometry: Stoichiometry993
component: U6 ATAC snRNP (name copied from entity in Homo sapiens)
component: U4 ATAC snRNP (name copied from entity in Homo sapiens)
xref: UnificationXref3693
cellular location: GO_0005654
comment: Reactome DB_ID: 5610483

UnificationXref1536
type: UnificationXref
id: REACT_90237
db: Reactome
id version: 4
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_90237.4

Evidence507
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/7601352
xref: http://identifiers.org/pubmed/11784853
xref: http://identifiers.org/pubmed/9405375
xref: http://identifiers.org/pubmed/3667620
xref: http://identifiers.org/pubmed/8612591
comment: Formation of the open complex exposes the template strand to the catalytic center of the RNA polymerase II enzyme. This facilitates formation of the first phosphodiester bond, which marks transcription initiation. As a result of this, the TFIIB basal transcription factor dissociates from the initiation complex. The open transcription initiation complex is unstable and can revert to the closed state. Initiation at this stage requires continued (d)ATP-hydrolysis by TFIIH. Dinucleotide transcripts are not stably associated with the transcription complex. Upon dissociation they form abortive products. The transcription complex is also sensitive to inhibition by small oligo-nucleotides. Dinucleotides complementary to position -1 and +1 in the template can also direct first phosphodiester bond formation. This reaction is independent on the basal transcription factors TFIIE and TFIIH and does not involve open complex formation. This reaction is sensitive to inhibition by single-stranded oligonucleotides.

UnificationXref1535
type: UnificationXref
id: 5607965
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607965

Evidence506
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: At the beginning of this reaction, 1 molecule of 'Pol II Initiation complex with phosphodiester-PPi intermediate' is present. At the end of this reaction, 1 molecule of 'pyrophosphate', and 1 molecule of 'pol II transcription complex' are present. This reaction takes place in the 'nucleus'.

UnificationXref1538
type: UnificationXref
id: REACT_88805
db: Reactome
id version: 4
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_88805.4

http://identifiers.org/pubmed/17402747
type: PublicationXref
id: 17402747
author: Magni, G
author: Franchetti, P
author: Cimadamore, F
author: Cappellacci, L
author: Orsomando, G
author: Scotti, S
author: Sorci, L
author: Petrelli, R
db: Pubmed
title: Initial-rate kinetics of human NMN-adenylyltransferases: substrate and metal ion specificity, inhibition by products and multisubstrate analogues, and isozyme contributions to NAD+ biosynthesis
source: Biochemistry 46:4912-22
year: 2007

UnificationXref1537
type: UnificationXref
id: 5608109
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608109

UnificationXref3679
type: UnificationXref
id: 5610417
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610417

UnificationXref1539
type: UnificationXref
id: 5618003
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618003

UnificationXref3678
type: UnificationXref
id: Q02260
db: UniProt

Covalent CE:GMP intermediate complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry968
component stoichiometry: Stoichiometry967
component: SmallMolecule136
component: CE:Pol II CTD:Spt5 complex (name copied from entity in Homo sapiens)
xref: UnificationXref3632
cellular location: GO_0005654
comment: Reactome DB_ID: 5610674

Capping complex (intermediate) (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry969
component stoichiometry: Stoichiometry966
component stoichiometry: Stoichiometry970
component: PhysicalEntity89
component: Covalent CE:GMP intermediate complex (name copied from entity in Homo sapiens)
component: PhysicalEntity5
xref: UnificationXref3633
cellular location: GO_0005654
comment: Reactome DB_ID: 5610675

Capping complex (with freed 5'- GMP) (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry974
component stoichiometry: Stoichiometry975
component stoichiometry: Stoichiometry976
component: CE:Pol II CTD:Spt5 complex (name copied from entity in Homo sapiens)
component: PhysicalEntity91
component: PhysicalEntity5
xref: UnificationXref3645
cellular location: GO_0005654
comment: Reactome DB_ID: 5610681

Capping complex (GpppN..) (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry971
component stoichiometry: Stoichiometry972
component stoichiometry: Stoichiometry973
component: CE:Pol II CTD:Spt5 complex (name copied from entity in Homo sapiens)
component: PhysicalEntity90
component: PhysicalEntity5
xref: UnificationXref3640
cellular location: GO_0005654
comment: Reactome DB_ID: 5610678

capped, methylated pre-mRNA:CBC Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry979
component stoichiometry: Stoichiometry980
component stoichiometry: Stoichiometry981
component: Cap Binding Complex (CBC) (name copied from entity in Homo sapiens)
component: PhysicalEntity92
component: RNA Polymerase II (unphosphorylated):TFIIF complex (name copied from entity in Homo sapiens)
xref: UnificationXref3665
cellular location: GO_0005654
comment: Reactome DB_ID: 5609152

mRNA capping factors (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry978
component stoichiometry: Stoichiometry977
component: Protein1049
component: Protein1050
xref: UnificationXref3654
cellular location: GO_0005654
comment: Reactome DB_ID: 5610683

U4 ATAC:U5:U6 ATAC Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry997
component stoichiometry: Stoichiometry1008
component: U4 ATAC snRNP:U6 ATAC snRNP (name copied from entity in Homo sapiens)
component: U5 snRNP (name copied from entity in Homo sapiens)
xref: UnificationXref3711
cellular location: GO_0005654
comment: Reactome DB_ID: 5610484

mRNA (N6-adenosine)-methyltransferase (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry982
component stoichiometry: Stoichiometry983
component: Protein1101
component: PhysicalEntity28
xref: UnificationXref3668
cellular location: GO_0005654
comment: Reactome DB_ID: 5609157

UnificationXref11019
type: UnificationXref
id: 5610771
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610771

UnificationXref11018
type: UnificationXref
id: 5610770
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610770

U6 ATAC snRNP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry992
component stoichiometry: Stoichiometry984
component: snRNP Sm core complex (name copied from entity in Homo sapiens)
component: PhysicalEntity93
xref: UnificationXref3689
cellular location: GO_0005654
comment: Reactome DB_ID: 5610482

UnificationXref11017
type: UnificationXref
id: P31381
db: UniProt

snRNP Sm core complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry989
component stoichiometry: Stoichiometry988
component stoichiometry: Stoichiometry991
component stoichiometry: Stoichiometry990
component stoichiometry: Stoichiometry986
component stoichiometry: Stoichiometry987
component stoichiometry: Stoichiometry985
component: Protein1105
component: Protein1106
component: Protein1107
component: Protein1108
component: Protein1102
component: Protein1103
component: Protein1104
xref: UnificationXref3688
cellular location: GO_0005654
comment: Reactome DB_ID: 5610423

UnificationXref11016
type: UnificationXref
id: 5610769
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610769

UnificationXref11015
type: UnificationXref
id: REACT_2401
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2401.2

UnificationXref11014
type: UnificationXref
id: 83923
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=83923

UnificationXref3663
type: UnificationXref
id: 77507
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=77507

http://identifiers.org/pubmed/2069720
type: PublicationXref
id: 2069720
author: Myöhänen, S
author: Kauppinen, L
author: Jänne, J
author: Wahlfors, J
author: Alhonen, L
db: Pubmed
title: Human spermidine synthase gene: structure and chromosomal localization
source: DNA Cell Biol 10:467-74
year: 1991

UnificationXref11013
type: UnificationXref
id: REACT_5346
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5346.2

Evidence510
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/7601352
xref: http://identifiers.org/pubmed/9405375
comment: Formation of phosphodiester bonds nine and ten creates RNA products, which do not dissociate from the RNA pol II initiation complex. The transcription complex has enter the productive elongation phase. TFIIH and ATP-hydrolysis are required for efficient promoter escape. The open region (ââ¬Åtranscription bubbleââ¬Â) expands concomitant with the site of RNA-extension. The region upstream from the transcription start site (-9 to -3) collapses to the double-stranded state. TFIIH remains associated to the RNA pol II initiation complex.

UnificationXref3664
type: UnificationXref
id: REACT_3578
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3578.1

UnificationXref11012
type: UnificationXref
id: 83922
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=83922

Evidence511
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9353262
xref: http://identifiers.org/pubmed/7601352
xref: http://identifiers.org/pubmed/11486021
xref: http://identifiers.org/pubmed/11433015
comment: RNA polymerase II transcription complexes are susceptible to transcriptional stalling and arrest, when extending nascent transcripts to 30-nt. This susceptibility depends on presence on down-stream DNA, the particular DNA-sequence of the template and presence of transcription factors. Transcription factor TFIIH remains associated to the RNA pol II elongation complex until position +30. At this stage transcription elongation factor TFIIS can rescue stalled transcription elongation complexes. The transcription bubble varies between 13- and 22-nt in size.

UnificationXref3665
type: UnificationXref
id: 5609152
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609152

UnificationXref11011
type: UnificationXref
id: REACT_4660
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4660.2

Evidence512
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9405375
comment: RNA Polymerase II promoter escape occurs after the first phosphodiester bond has been created.

UnificationXref3666
type: UnificationXref
id: P41833
db: UniProt

UnificationXref11010
type: UnificationXref
id: 83921
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=83921

UnificationXref1520
type: UnificationXref
id: 5607937
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607937

UnificationXref1521
type: UnificationXref
id: 5607938
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607938

Evidence514
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: At the beginning of this reaction, 1 molecule of 'Pol II transcription complex containing transcript to +30' is present. At the end of this reaction, 1 molecule of 'Pol II transcription complex containing extruded transcript to +30' is present. This reaction takes place in the 'nucleus'.

UnificationXref3660
type: UnificationXref
id: REACT_207782
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_207782.2

Evidence515
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Phosphorylation of serine 5 residue at the CTD of pol II largest subunit is an important step signaling the end of initiation and escape into processive elongation processes. Cdk7 protein subunit of TFIIH phosphorylates RNA Pol II CTD serine 5 residues on its heptad repeats.

UnificationXref3661
type: UnificationXref
id: 5618127
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618127

Evidence516
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: At the beginning of this reaction, 1 molecule of 'mRNA capping enzyme', and 1 molecule of 'Pol II transcription complex with (ser5) phosphorylated CTD containing extruded transcript to +30' are present. At the end of this reaction, 1 molecule of 'RNA Pol II with phosphorylated CTD: CE complex' is present. This reaction takes place in the 'nucleus'.

UnificationXref3662
type: UnificationXref
id: REACT_240372
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_240372.1

UnificationXref1525
type: UnificationXref
id: 5607942
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607942

Evidence518
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: The capping enzyme interacts with the Spt5 subunit of transcription elongation factor DSIF. This interaction may couple the capping reaction with promoter escape or elongation, thereby acting as a ââ¬Åcheckpointââ¬Â to assure that capping has occurred before the polymerase proceeds to make the rest of the transcript.

UnificationXref1524
type: UnificationXref
id: 5607941
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607941

Evidence517
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: At the beginning of this reaction, 1 molecule of 'RNA Pol II with phosphorylated CTD: CE complex' is present. At the end of this reaction, 1 molecule of 'RNA Pol II with phosphorylated CTD: CE complex with activated GT' is present. This reaction takes place in the 'nucleus'.

UnificationXref1523
type: UnificationXref
id: 5607940
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607940

UnificationXref1522
type: UnificationXref
id: 5607939
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607939

Evidence519
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: To facilitate co-transcriptional capping, and thereby restrict the cap structure to RNAs made by RNA polymerase II, the capping enzymes bind directly to the RNA polymerase II. The C-terminal domain of the largest Pol II subunit contains several phosphorylation sites on its heptapeptide repeats. The capping enzyme guanylyltransferase and the methyltransferase bind specifically to CTD phosphorylated at Serine 5 within the CTD. Kinase subunit of TFIIH, Cdk7, catalyzes this phosphorylation event that occurs near the promoter. In addition, it has been shown that binding of capping enzyme to the Serine-5 phosphorylated CTD stimulates guanylyltransferase activity in vitro.

UnificationXref1529
type: UnificationXref
id: 5607946
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607946

UnificationXref3668
type: UnificationXref
id: 5609157
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609157

UnificationXref1528
type: UnificationXref
id: 5607945
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607945

UnificationXref3667
type: UnificationXref
id: 5609156
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609156

UnificationXref1527
type: UnificationXref
id: 5607944
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607944

UnificationXref1526
type: UnificationXref
id: 5607943
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607943

UnificationXref3669
type: UnificationXref
id: 5609159
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609159

U12 snRNP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1010
component stoichiometry: Stoichiometry1009
component stoichiometry: Stoichiometry1016
component stoichiometry: Stoichiometry1017
component: snRNP Sm core complex (name copied from entity in Homo sapiens)
component: PhysicalEntity95
component: PhysicalEntity28
component: SF3B (name copied from entity in Homo sapiens)
xref: UnificationXref3723
cellular location: GO_0005654
comment: Reactome DB_ID: 5610446

ATAC A Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1023
component stoichiometry: Stoichiometry1024
component stoichiometry: Stoichiometry1019
component stoichiometry: Stoichiometry1018
component stoichiometry: Stoichiometry1020
component: PhysicalEntity28
component: Protein1121
component: U12 snRNP (name copied from entity in Homo sapiens)
component: capped, methylated pre-mRNA:CBC Complex (name copied from entity in Homo sapiens)
component: U11 snRNP (name copied from entity in Homo sapiens)
xref: UnificationXref3729
cellular location: GO_0005654
comment: Reactome DB_ID: 5610447

U5 snRNP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry998
component stoichiometry: Stoichiometry1006
component stoichiometry: Stoichiometry1007
component stoichiometry: Stoichiometry1004
component stoichiometry: Stoichiometry1005
component stoichiometry: Stoichiometry1002
component stoichiometry: Stoichiometry999
component stoichiometry: Stoichiometry1003
component stoichiometry: Stoichiometry1000
component stoichiometry: Stoichiometry1001
component: Protein1116
component: Protein1113
component: Protein1112
component: snRNP Sm core complex (name copied from entity in Homo sapiens)
component: Protein1115
component: Protein1114
component: PhysicalEntity28
component: Protein1110
component: Protein1111
component: Protein1109
xref: UnificationXref3710
cellular location: GO_0005654
comment: Reactome DB_ID: 5610480

U4 ATAC snRNP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry995
component stoichiometry: Stoichiometry994
component: PhysicalEntity94
component: snRNP Sm core complex (name copied from entity in Homo sapiens)
xref: UnificationXref3692
cellular location: GO_0005654
comment: Reactome DB_ID: 5610481

ATAC C Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1033
component stoichiometry: Stoichiometry1027
component stoichiometry: Stoichiometry1029
component stoichiometry: Stoichiometry1028
component stoichiometry: Stoichiometry1032
component stoichiometry: Stoichiometry1031
component stoichiometry: Stoichiometry1030
component: U6 ATAC snRNP (name copied from entity in Homo sapiens)
component: PhysicalEntity28
component: Protein1121
component: U12 snRNP (name copied from entity in Homo sapiens)
component: U5 snRNP (name copied from entity in Homo sapiens)
component: capped, methylated pre-mRNA:CBC Complex (name copied from entity in Homo sapiens)
component: U11 snRNP (name copied from entity in Homo sapiens)
xref: UnificationXref3733
cellular location: GO_0005654
comment: Reactome DB_ID: 5610486

ATAC B Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1025
component stoichiometry: Stoichiometry1026
component: ATAC A Complex (name copied from entity in Homo sapiens)
component: U4 ATAC:U5:U6 ATAC Complex (name copied from entity in Homo sapiens)
xref: UnificationXref3730
cellular location: GO_0005654
comment: Reactome DB_ID: 5610485

U11 snRNP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1022
component stoichiometry: Stoichiometry1021
component: snRNP Sm core complex (name copied from entity in Homo sapiens)
component: PhysicalEntity96
xref: UnificationXref3726
cellular location: GO_0005654
comment: Reactome DB_ID: 5610424

SF3B (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1015
component stoichiometry: Stoichiometry1011
component stoichiometry: Stoichiometry1012
component stoichiometry: Stoichiometry1013
component stoichiometry: Stoichiometry1014
component: Protein1117
component: Protein1119
component: Protein1118
component: PhysicalEntity28
component: Protein1120
xref: UnificationXref3720
cellular location: GO_0005654
comment: Reactome DB_ID: 5610445

UnificationXref11005
type: UnificationXref
id: REACT_5567
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5567.3

UnificationXref11004
type: UnificationXref
id: 83908
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=83908

post exon ligation complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1036
component stoichiometry: Stoichiometry1035
component stoichiometry: Stoichiometry1034
component stoichiometry: Stoichiometry1037
component: PhysicalEntity97
component: PhysicalEntity28
component: Protein1121
component: capped, methylated pre-mRNA:CBC Complex (name copied from entity in Homo sapiens)
xref: UnificationXref3740
cellular location: GO_0005654
comment: Reactome DB_ID: 5610490

UnificationXref11007
type: UnificationXref
id: REACT_4381
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4381.2

CARS dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1038
component: Protein1124
xref: UnificationXref3776
cellular location: GO_0005829
comment: Reactome DB_ID: 5613522

UnificationXref11006
type: UnificationXref
id: 83948
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=83948

GARS dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1039
component: Protein1125
xref: UnificationXref3790
cellular location: GO_0005829
comment: Reactome DB_ID: 5613574

UnificationXref11009
type: UnificationXref
id: REACT_3375
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3375.2

UnificationXref11008
type: UnificationXref
id: 83920
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=83920

http://identifiers.org/pubmed/17590538
type: PublicationXref
id: 17590538
author: Ball, E
author: Takeuchi, M
author: Harigai, M
author: Kamatani, N
author: Furuichi, K
author: Abe, J
author: Momohara, S
db: Pubmed
title: Cloning and characterization of DPPL1 and DPPL2, representatives of a novel type of mammalian phosphatidate phosphatase
source: Gene 399:174-80
year: 2007

Evidence526
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16732292
xref: http://identifiers.org/pubmed/16362057
comment: All characterised lysine demethylases other than KDM1A belong to the jumonji C-domain (JmjC) containing family, members of the Cupin superfamily of mononuclear Fe (II)-dependent oxygenases. They require 2-oxoglutarate (2-OG) and molecular oxygen as co-substrates, producing succinate and carbon dioxide. This hydroxylation-based mechanism does not require a protonatable lysine epsilon-amine group and consequently JmjC-containing demethylases are able to demethylate tri-, di- and monomethylated lyines. The first reported JmjC-containing demethylases were KDM2A and KDM2B (JHDM1A/B, FBXL11/10). These demethylate lysine-37 of histone H3 when mono- or di-methylated (H3K36Me1/2) (Tsukada et al. 2006). KDM4A (JHDM3A) can demethylate mono-, di and trimethylated lysine-37 of histone H3 (Klose et al. 2006).

UnificationXref3650
type: UnificationXref
id: REACT_3845
db: Reactome
id version: 4
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3845.4

Evidence527
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/22615488
xref: http://identifiers.org/pubmed/21532585
xref: http://identifiers.org/pubmed/20622853
xref: http://identifiers.org/pubmed/20346720
xref: http://identifiers.org/pubmed/20208542
xref: http://identifiers.org/pubmed/20421419
xref: http://identifiers.org/pubmed/16603237
xref: http://identifiers.org/pubmed/20622854
xref: http://identifiers.org/pubmed/19843542
xref: http://identifiers.org/pubmed/20084082
xref: http://identifiers.org/pubmed/20023638
xref: http://identifiers.org/pubmed/20129925
comment: All characterized lysine demethylases other than KDM1A belong to the jumonjiC domain (JmjC) containing family.The JmjC KDMs are members of the Cupin superfamily of mononuclear Fe (II) dependent oxygenases, which are characterized by the presence of a double-stranded beta-helix core fold. The JmjC KDMs require 2 oxoglutarate (2 OG) and molecular oxygen as co substrates, producing, along with formaldehyde, succinate and carbon dioxide. This hydroxylation based mechanism does not require a protonatable lysine epsilon-amine group and consequently JmjC containing demethylases are able to catalyse demethylateion of tri , di and monomethylated lysines. KDM3A (JHDM2A), KDM3B (JHDM2B), KDM7A (JHDM1D), PHF8 (JHDM1E) and PHF2 when complexed with ARID5B (Wen et al. 2010, Baba et al. 2011) are specific for mono or di-methylated lysine-10 on histone H3 (H3K9Me1/2) (Yamane et al. 2006, Kim et al. 2012, Horton et al. 2010, Huang et al. 2010, Loenarz et al. 2008, Feng et al. 2010, Fortschegger et al. 2010, Qi et al. 2010).

UnificationXref3651
type: UnificationXref
id: CHEBI:16680
db: ChEBI

UnificationXref1510
type: UnificationXref
id: REACT_235168
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_235168.1

Evidence525
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Transcription by RNA Polymerase I, RNA Polymerase III and transcription from mitochondrial promoters.

UnificationXref11001
type: UnificationXref
id: 83928
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=83928

Evidence522
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11940650
xref: http://identifiers.org/pubmed/10916156
comment: Transcription elongation by RNA polymerase II (RNAPII) is controlled by a number of trans-acting transcription elongation factors as well as by cis-acting elements. Transcription elongation is a rate-limiting step for proper mRNA production in which the phosphorylation of Pol II CTD is a crucial biochemical event. The role of CTD phosphorylation in transcription by Pol II is greatly impaired by protein kinase inhibitors such as 5,6-dichloro-1- ribofuranosylbenzimidazole (DRB), which block CTD phosphorylation and induce arrest of elongating Pol II. DRB-sensitive activation Pol II CTD during elongation has enabled the isolation of two sets of factors -Negative Elongation Factors (NELF) and DRB sensitivity inducing factor (DSIF). P-Tefb is a DRB-sensitive, cyclin-dependent CTD kinase composed of Cdk9 that carries out Serine-2 phosphorylation of Pol II CTD during elongation. The mechanism by which DSIF, NELF and P-TEFb act together in Pol II-regulated elongation is yet to be fully understood. Various biochemical evidences point to a model in which DSIF and NELF negatively regulate elongation through interactions with polymerase containing a hypophosphorylated CTD. Subsequent phosphorylation of the Pol II CTD by P-Tefb might promote elongation by inhibiting interactions of DSIF and NELF with the elongation complex.

UnificationXref3654
type: UnificationXref
id: 5610683
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610683

UnificationXref11000
type: UnificationXref
id: CHEBI:17748
db: ChEBI

Evidence523
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/14550628
xref: http://identifiers.org/pubmed/12676794
xref: http://identifiers.org/pubmed/11018013
comment: The mechanisms governing the process of elongation during eukaryotic mRNA synthesis are being unraveled by recent studies. These studies have led to the expected discovery of a diverse collection of transcription factors that directly regulate the activities of RNA Polymerase II and unexpected discovery of roles for many elongation factors in other basic processes like DNA repair, recombination, etc. The transcription machinery and structural features of the major RNA polymerases are conserved across species. The genes active during elongation fall under different classes like, housekeeping, cell-cycle regulated, development and differentiation specific genes etc. The list of genes involved in elongation has been growing in recent times, and include: -TFIIS,DSIF, NELF, P-Tefb etc. that are involved in drug induced or sequence-dependent arrest - TFIIF, ELL, elongin, elongator etc. that are involved in increasing the catalytic rate of elongation by altering the Km and/or the Vmax of Pol II -FACT, Paf1 and other factors that are involved chromatin modification - DNA repair proteins, RNA processing and export factors, the 19S proteasome and a host of other factors like Spt5-Spt5, Paf1, and NELF complexes, FCP1P etc. (Arndt and Kane, 2003). Elongation also represents processive phase of transcription in which the activities of several mRNA processing factors are coupled to transcription through their binding to RNA polymerase (Pol II). One of the key events that enables this interaction is the differential phosphorylation of Pol II CTD. Phosphorylation pattern of CTD changes during transcription, most significantly at the beginning and during elongation process. TFIIH-dependent Ser5 phosphorylation is observed primarily at promoter regions while P-Tefb mediated Ser2 phosphorylation is seen mainly in the coding regions, during elongation. Experimental evidence suggests a dynamic association of RNA processing factors with differently modified forms of the polymerase during…

UnificationXref3655
type: UnificationXref
id: 5610685
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610685

UnificationXref11003
type: UnificationXref
id: 5610768
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610768

Evidence520
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12370301
comment: FCP1 dephosphorylates RNAP II in ternary elongation complexes as well as in solution and, therefore, is thought to function in the recycling of RNAP II during the transcription cycle. Biochemical experiments suggest that human FCP1 targets CTDs that are phosphorylated at serine 2 (CTD-serine 2) and/or CTD-serine 5. It is also observed to stimulate elongation independent of its catalytic activity. Dephosphorylation of Ser2 - phosphorylated Pol II results in hypophosphorylated form that disengages capping enzymes (CE).

UnificationXref3652
type: UnificationXref
id: 77502
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=77502

UnificationXref11002
type: UnificationXref
id: REACT_5250
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5250.2

Evidence521
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9450929
xref: http://identifiers.org/pubmed/12653964
comment: DSIF is a heterodimer consisting of hSPT4 (human homolog of yeast Spt4- p14) and hSPT5 (human homolog of yeast Spt5-p160). DSIF association with Pol II may be enabled by Spt5 binding to Pol II creating a scaffold for NELF binding (Wada et al.,1998). Spt5 subunit of DSIF can be phosphorylated by P-TEFb.

UnificationXref3653
type: UnificationXref
id: REACT_5201
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5201.3

UnificationXref1516
type: UnificationXref
id: 5607929
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607929

UnificationXref3659
type: UnificationXref
id: 5610686
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610686

UnificationXref1515
type: UnificationXref
id: 5607923
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607923

UnificationXref3658
type: UnificationXref
id: REACT_219645
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_219645.2

UnificationXref1518
type: UnificationXref
id: 5607932
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607932

UnificationXref3657
type: UnificationXref
id: 5610687
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610687

UnificationXref1517
type: UnificationXref
id: 5607931
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607931

UnificationXref3656
type: UnificationXref
id: REACT_254873
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_254873.1

UnificationXref1512
type: UnificationXref
id: REACT_234989
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_234989.1

UnificationXref1511
type: UnificationXref
id: 5617997
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617997

UnificationXref1514
type: UnificationXref
id: 5607919
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607919

Evidence529
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17310255
xref: http://identifiers.org/pubmed/17351631
xref: http://identifiers.org/pubmed/17311883
xref: http://identifiers.org/pubmed/17320161
xref: http://identifiers.org/pubmed/17320160
xref: http://identifiers.org/pubmed/17320163
comment: All characterized lysine demethylases other than KDM1A belong to the jumonjiC domain (JmjC) containing family.The JmjC KDMs are members of the Cupin superfamily of mononuclear Fe (II) dependent oxygenases, which are characterized by the presence of a double-stranded beta-helix core fold. The JmjC KDMs require 2 oxoglutarate (2 OG) and molecular oxygen as co substrates, producing, along with formaldehyde, succinate and carbon dioxide. This hydroxylation based mechanism does not require a protonatable lysine epsilon-amine group and consequently JmjC containing demethylases are able to demethylate tri , di and monomethylated lysines. KDM5A-D (JARID1A-D) catalyse the demethylation of di- or tri-methylated lysine-5 of histone H3 (H3K4Me2/3) (Christensen et al. 2007, Klose et al. 2007, Lee et al. 2007, Secombe et al. 2007, Seward et al. 2007, Iwase et al. 2007).

UnificationXref1513
type: UnificationXref
id: P54784
db: UniProt

Evidence528
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16732292
xref: http://identifiers.org/pubmed/16603238
xref: http://identifiers.org/pubmed/16738407
xref: http://identifiers.org/pubmed/16732293
comment: All characterized lysine demethylases other than KDM1A belong to the jumonjiC domain (JmjC) containing family.The JmjC KDMs are members of the Cupin superfamily of mononuclear Fe (II) dependent oxygenases, which are characterized by the presence of a double-stranded beta-helix core fold. The JmjC KDMs require 2 oxoglutarate (2 OG) and molecular oxygen as co substrates, producing, along with formaldehyde, succinate and carbon dioxide. This hydroxylation based mechanism does not require a protonatable lysine e amine group and consequently JmjC containing demethylases are able to demethylate tri , di and monomethylated lysines. KDM4A-D (JMJD2A-D/JHDM3A-D) catalyse the demethylation of di- or tri-methylated histone H3 at lysine-10 (H3K9Me2/3) (Cloos et al. 2006, Fodor et al. 2006, Whetstine et al. 2007), with a strong preference for Me3 (Whetstine et al. 2007). KDM4A (JHDM3A) can also demethylate lysine-37 of histone H3 (H3K36Me2/3) (Klose et al. 2006).

PPA1 dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1047
component: Protein1136
xref: UnificationXref3875
cellular location: GO_0005829
comment: Reactome DB_ID: 5609062

YARS dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1045
component: Protein1134
xref: UnificationXref3857
cellular location: GO_0005829
comment: Reactome DB_ID: 5613536

DARS2 dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1048
component: Protein1144
xref: UnificationXref3931
cellular location: GO_0005759
comment: Reactome DB_ID: 5613656

SARS dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1042
component: Protein1131
xref: UnificationXref3824
cellular location: GO_0005829
comment: Reactome DB_ID: 5613543

Release of apoptotic factors from the mitochondria
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction23
evidence: Evidence39
xref: UnificationXref312
xref: UnificationXref311
pathway order: PathwayStep37
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref1519
type: UnificationXref
id: 5607936
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607936

FARS A2B2 tetramer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1041
component stoichiometry: Stoichiometry1040
component: Protein1129
component: Protein1130
xref: UnificationXref3813
cellular location: GO_0005829
comment: Reactome DB_ID: 5613509

WARS dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1044
component: Protein1133
xref: UnificationXref3846
cellular location: GO_0005829
comment: Reactome DB_ID: 5613529

TARS dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1043
component: Protein1132
xref: UnificationXref3835
cellular location: GO_0005829
comment: Reactome DB_ID: 5613556

FMO oxidizes nucleophiles
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction984
pathway component: BiochemicalReaction985
pathway component: BiochemicalReaction986
evidence: Evidence1607
xref: UnificationXref10392
xref: UnificationXref10393
pathway order: PathwayStep1590
pathway order: PathwayStep1588
pathway order: PathwayStep1589
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

Evidence530
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/20084082
xref: http://identifiers.org/pubmed/17851529
xref: http://identifiers.org/pubmed/20023638
xref: http://identifiers.org/pubmed/17761849
xref: http://identifiers.org/pubmed/17713478
xref: http://identifiers.org/pubmed/17825402
xref: http://identifiers.org/pubmed/17500065
comment: All characterized lysine demethylases other than KDM1A belong to the jumonjiC domain (JmjC) containing family.The JmjC KDMs are members of the Cupin superfamily of mononuclear Fe (II) dependent oxygenases, which are characterized by the presence of a double-stranded beta-helix core fold. The JmjC KDMs require 2 oxoglutarate (2 OG) and molecular oxygen as co substrates, producing, along with formaldehyde, succinate and carbon dioxide. This hydroxylation based mechanism does not require a protonatable lysine e amine group and consequently JmjC containing demethylases are able to demethylate tri , di and monomethylated lysines. KDM6A (UTX), KDM6B (JMJD3) and KDM7A (JHDM1D) catalyse the demethylation of di or tri-methylated lysine-28 of histone H3 (H3K27Me2/3) (Agger et al. 2007, Cho et al. 2007, De Santra et al. 2007, Hong et al. 2007, Lan et al. 2007, Lee et al. 2007, Horton et al. 2010, Huang et al. 2010).

Evidence535
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15598472
xref: http://identifiers.org/pubmed/21342762
comment: Chromatin organization refers to the composition and conformation of complexes between DNA, protein and RNA. It is determined by processes that result in the specification, formation or maintenance of the physical structure of eukaryotic chromatin. These processes include histone modification, DNA modification, and transcription. The modifications are bound by specific proteins that alter the conformation of chromatin.

Evidence536
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: The capping enzyme binds the 5'-end of the nascent transcript soon after it is synthesized on the DNA template, and results in the formation of the capping complex along with the C-terminal domain of RNA polymerase II, and Spt5.

Evidence537
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9512541
comment: After the capping complex is formed, the RNA triphosphatase activity of the capping enzyme hydrolyzes the 5'-end phosphate group of the nascent mRNA transcript to a diphosphate. The RNA triphosphatase (RTP) domain of mammalian capping enzyme is a member of a superfamily of phosphatases that include the protein tyrosine phosphatases, some lipid phosphatases, and several nucleic acid phosphatases. This family uses a conserved nucleophilic cysteine residue to attack the target phosphate. A transient phospho-cysteinyl enzyme intermediate is then hydrolyzed to regenerate the enzyme active site. It should be noted that while higher eukaryotic capping enzymes use PTP-like triphosphatase domains, the yeast triphosphatases are a completely different class of enzymes. The yeast RTPs are metal-dependent phosphatases. RNA 5'-triphosphatase (RTP) catalyzed first reaction can be represented as:pppN(pN)n + GTP -> ppN(pN)n + Pi; (n=20-25)

Evidence538
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9512541
comment: A highly conserved lysine within the guanylyltransferase (GT) site of the mRNA capping enzyme attacks the alpha-phosphate of GTP. An enzyme-GMP covalent intermediate is formed.

UnificationXref3640
type: UnificationXref
id: 5610678
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610678

Evidence531
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16732292
xref: http://identifiers.org/pubmed/16603238
xref: http://identifiers.org/pubmed/17320163
xref: http://identifiers.org/pubmed/17851529
xref: http://identifiers.org/pubmed/17761849
xref: http://identifiers.org/pubmed/17713478
xref: http://identifiers.org/pubmed/17825402
xref: http://identifiers.org/pubmed/16738407
xref: http://identifiers.org/pubmed/17500065
xref: http://identifiers.org/pubmed/16732293
xref: http://identifiers.org/pubmed/22615488
xref: http://identifiers.org/pubmed/17310255
xref: http://identifiers.org/pubmed/23142576
xref: http://identifiers.org/pubmed/17947579
xref: http://identifiers.org/pubmed/17351631
xref: http://identifiers.org/pubmed/17311883
xref: http://identifiers.org/pubmed/11165500
xref: http://identifiers.org/pubmed/17320161
xref: http://identifiers.org/pubmed/16603237
xref: http://identifiers.org/pubmed/17320160
xref: http://identifiers.org/pubmed/19574390
xref: http://identifiers.org/pubmed/16362057
xref: http://identifiers.org/pubmed/11740497
xref: http://identifiers.org/pubmed/16261189
comment: Histone lysine demethylases (KDMs) are able to reverse N-methylations of histones and probably other proteins. To date KDMs have been demonstrated to catalyse demethylation of N-epsilon methylated lysine residues. Biochemically there are two distinct groups of N-epsilon methylated lysine demethylases with different catalytic mechanisms, both of which result in methyl group oxidation to produce formaldhyde. KDM1A, formerly known as Lysine Specific Demethylase 1 (LSD1), belongs to the flavin adenine dinucleotide (FAD)-dependent amino oxidase family. The KDM1A reaction mechanism requires a protonatable lysine epsilon-amine group, not available in trimethylated lysines, which consequently are not KDM1 substrates. Other KDMs belong to the Jumonji C (JmjC) -domain containing family. These are members of the Cupin superfamily of mononuclear Fe (II)-dependent oxygenases, which are characterised by the presence of a double-stranded beta-helix core fold. They require 2-oxoglutarate (2OG) and molecular oxygen as co-substrates, producing, in addition to formaldehyde, succinate and carbon dioxide. This hydroxylation-based mechanism does not require a protonatable lysine epsilon-amine group and consequently JmjC-containing demethylases are able to demethylate tri-, di- and monomethylated lysines. The coordinates of post-translational modifications represented and described here follow UniProt standard practice whereby coordinates refer to the translated protein before any further processing. Histone literature typically refers to coordinates of the protein after the initiating methionine has been removed. Therefore the coordinates of post-translated residues in the Reactome database and described here are frequently +1 when compared with the literature. In general, methylation at histone H3 lysine-5 (H3K4) and lysine-37 (H3K36), including di- and trimethylation at these sites, has been linked to actively transcribed genes (reviewed in Martin & Zhang 2005). In contrast, lysine-10 …

UnificationXref3641
type: UnificationXref
id: 5610680
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610680

Evidence532
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/22231400
comment: RBBP7, a central component of the co-repressor complexes Sin3a, NURD and PRC2, can bind histone H3 arginine-3 (H3R2). Symmetrical dimethylation of this residue excludes RBBP7 binding but enhances binding of WDR5, a common component of the coactivator complexes MLL, SET1A, SET1B, NLS1 and ATAC (Migliori et al. 2012).

UnificationXref3642
type: UnificationXref
id: REACT_219962
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_219962.2

Evidence533
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15186775
xref: http://identifiers.org/pubmed/843361
xref: http://identifiers.org/pubmed/17898715
xref: http://identifiers.org/pubmed/19150423
xref: http://identifiers.org/pubmed/15485929
xref: http://identifiers.org/pubmed/16103216
xref: http://identifiers.org/pubmed/18079182
xref: http://identifiers.org/pubmed/23235912
xref: http://identifiers.org/pubmed/17218272
xref: http://identifiers.org/pubmed/17898714
xref: http://identifiers.org/pubmed/21502321
comment: Arginine methylation is a common post-translational modification; around 2% of arginine residues are methylated in rat liver nuclei (Boffa et al. 1977). Arginine can be methylated in 3 different ways: monomethylarginine (MMA); NG,NG-asymmetric dimethylarginine (ADMA) and NG,N'G-symmetric dimethylarginine (SDMA). The formation of MMA, ADMA and SDMA in mammalian cells is carried out by members of a family of nine protein arginine methyltransferases (PRMTs) (Bedford & Clarke 2009). Type I, II and III PRMTs generate MMA on one of the two terminal guanidino nitrogen atoms. Subsequent generation of asymmetric dimethylarginine (ADMA) is catalysed by the type I enzymes PRMT1, PRMT2, PRMT3, co-activator-associated arginine methyltransferase 1 (CARM1), PRMT6 and PRMT8. Production of symmetric dimethylarginine (SDMA) is catalysed by the type II enzymes PRMT5 and PRMT7. On certain substrates, PRMT7 also functions as a type III enzyme, generating MMA only. PRMT9 activity has not been characterized. No known enzyme is capable of both ADMA and SDMA modifications. Arginine methylation is regarded as highly stable; no arginine demethylases are known (Yang & Bedford 2013). Most PRMTs methylate glycine- and arginine-rich (GAR) motifs in their substrates (Boffa et al. 1977). CARM1 methylates a proline-, glycine- and methionine-rich (PGM) motif (Cheng et al. 2007). PRMT5 can dimethylate arginine residues in GAR and PGM motifs (Cheng et al. 2007, Branscombe et al. 2001). PRMTs are widely expressed and are constitutively active as purified recombinant proteins. However, PRMT activity can be regulated through PTMs, association with regulatory proteins, subcellular compartmentalization and factors that affect enzyme-substrate interactions. The target sites of PRMTs are influenced by the presence of other PTMs on their substrates. The best characterized examples of this are for histones. Histone H3 lysine-18 acetylation (H3K18ac) primes the histone tail for asymmetric dimethylation at argini…

UnificationXref3643
type: UnificationXref
id: 111345
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111345

Evidence534
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17320507
xref: http://identifiers.org/pubmed/3622934
xref: http://identifiers.org/pubmed/22140112
xref: http://identifiers.org/pubmed/22449188
xref: http://identifiers.org/pubmed/18722564
xref: http://identifiers.org/pubmed/20197778
xref: http://identifiers.org/pubmed/12408966
xref: http://identifiers.org/pubmed/15687254
xref: http://identifiers.org/pubmed/6207931
xref: http://identifiers.org/pubmed/1921519
xref: http://identifiers.org/pubmed/23002134
xref: http://identifiers.org/pubmed/21332355
xref: http://identifiers.org/pubmed/9305837
comment: Eukaryotic DNA is associated with histone proteins and organized into a complex nucleoprotein structure called chromatin. This structure decreases the accessibility of DNA but also helps to protect it from damage. Access to DNA is achieved by highly regulated local chromatin decondensation. The 'building block' of chromatin is the nucleosome. This contains ~150 bp of DNA wrapped around a histone octamer which consists of two each of the core histones H2A, H2B, H3 and H4 in a 1.65 left-handed superhelical turn (Luger et al. 1997, Andrews & Luger 2011). Most organisms have multiple genes encoding the major histone proteins. The replication-dependent genes for the five histone proteins are clustered together in the genome in all metazoans. Human replication-dependent histones occur in a large cluster on chromosome 6 termed HIST1, a smaller cluster HIST2 on chromosome 1q21, and a third small cluster HIST3 on chromosome 1q42 (Marzluff et al. 2002). Histone genes are named systematically according to their cluster and location within the cluster. The 'major' histone genes are expressed primarily during the S phase of the cell cycle and code for the bulk of cellular histones. Histone variants are usually present as single-copy genes that are not restricted in their expression to S phase, contain introns and are often polyadenylated (Old & Woodland 1984 ). Some variants have significant differences in primary sequence and distinct biophysical characteristics that are thought to alter the properties of nucleosomes. Others localize to specific regions of the genome. Some variants can exchange with pre-existing major histones during development and differentiation, referred to as replacement histones (Kamakaka & Biggins 2005). These variants can become the predominant species in differentiated cells (Pina & Suau 1987, Wunsch et al. 1991). Histone variants may have specialized functions in regulating chromatin dynamics. The H2A histone family has the highest sequence divergence…

UnificationXref3644
type: UnificationXref
id: REACT_3793
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3793.1

UnificationXref1507
type: UnificationXref
id: REACT_2531
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2531.1

UnificationXref3646
type: UnificationXref
id: 5610682
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610682

UnificationXref1506
type: UnificationXref
id: 68424
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68424

UnificationXref3645
type: UnificationXref
id: 5610681
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610681

UnificationXref1505
type: UnificationXref
id: REACT_5885
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5885.1

UnificationXref3648
type: UnificationXref
id: CHEBI:15414
db: ChEBI

UnificationXref1504
type: UnificationXref
id: 30185
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=30185

UnificationXref3647
type: UnificationXref
id: REACT_226579
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_226579.2

UnificationXref1503
type: UnificationXref
id: CHEBI:16311
db: ChEBI

UnificationXref1502
type: UnificationXref
id: REACT_5621
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5621.1

Evidence539
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9512541
comment: The diphosphate 5'-end of the mRNA is joined to the GMP, releasing it from the enzyme. At this time, it is unclear how the RNA diphosphate end is transferred from the active site of the triphosphatase to the guanylyltransferase site. The covalent enzyme-GMP complex can form in the absence of RNA. Guanylyltransferase (GT) catalyzed second reaction can be represented as:ppN(pN)n + GTP -> GpppN(pN)n + PPi

UnificationXref3649
type: UnificationXref
id: 77087
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=77087

CIT1
type: ProteinReference
name: YNR001C
name: LYS6
name: GLU3
name: UniProt:P00890 CIT1
name: N2019
xref: UnificationXref11745
comment: CATALYTIC ACTIVITY Acetyl-CoA + H(2)O + oxaloacetate = citrate + CoA.PATHWAY Carbohydrate metabolism; tricarboxylic acid cycle; isocitrate from oxaloacetate: step 1/2.MISCELLANEOUS Citrate synthase is found in nearly all cells capable of oxidative metabolism.SIMILARITY Belongs to the citrate synthase family.
organism: http://identifiers.org/taxonomy/4932

UnificationXref1501
type: UnificationXref
id: 29604
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29604

UnificationXref1500
type: UnificationXref
id: CHEBI:16284
db: ChEBI

UnificationXref1509
type: UnificationXref
id: 5608112
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608112

UnificationXref1508
type: UnificationXref
id: 5608110
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608110

UnificationXref919
type: UnificationXref
id: 111845
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111845

UnificationXref918
type: UnificationXref
id: P32367
db: UniProt

YJU3
type: ProteinReference
name: UniProt:P28321
xref: UnificationXref142
organism: http://identifiers.org/taxonomy/4932

SequenceSite810
type: SequenceSite
position status: EQUAL
sequence position: 433

UnificationXref915
type: UnificationXref
id: REACT_5100
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5100.1

SequenceSite811
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref914
type: UnificationXref
id: 111840
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111840

SequenceSite812
type: SequenceSite
position status: EQUAL
sequence position: 433

UnificationXref917
type: UnificationXref
id: REACT_3916
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3916.2

SequenceSite813
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref916
type: UnificationXref
id: 111839
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111839

SequenceSite814
type: SequenceSite
position status: EQUAL
sequence position: 433

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: YJU3
data source: Provenance1
name: P28321
name: MAGL
name: Monoglyceride lipase
xref: UnificationXref143
feature: FragmentFeature27
cellular location: GO_0005886
comment: Reactome DB_ID: 5614127
display name: MGLL

Protein Kinase C, conventional
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref153
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5611263

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: UniProt:P24583
data source: Provenance1
name: Protein kinase C, alpha type
name: P24583
name: PKC-A
name: PKC-alpha
xref: UnificationXref150
feature: FragmentFeature28
cellular location: GO_0005829
comment: Reactome DB_ID: 5611166
display name: PRKCA

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: UniProt:P24583
data source: Provenance1
name: Protein kinase C, beta type
name: PKC-beta
name: P24583
name: PKC-B
xref: UnificationXref151
feature: FragmentFeature29
cellular location: GO_0005829
comment: Reactome DB_ID: 5611262
display name: PRKCB

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: UniProt:P24583
data source: Provenance1
name: P24583
name: PKC-gamma
name: Protein kinase C, gamma type
xref: UnificationXref152
feature: FragmentFeature30
cellular location: GO_0005829
comment: Reactome DB_ID: 5611168
display name: PRKCG

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: UniProt:P24583
data source: Provenance1
name: Protein kinase C, alpha type
name: P24583
name: PKC-A
name: PKC-alpha
xref: UnificationXref157
feature: FragmentFeature31
cellular location: GO_0005886
comment: Reactome DB_ID: 5611264
display name: PRKCA

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: UniProt:P24583
data source: Provenance1
name: P24583
name: nPKC-epsilon
name: Protein kinase C, epsilon type
xref: UnificationXref117
feature: FragmentFeature24
cellular location: GO_0005829
comment: Reactome DB_ID: 5612575
display name: PRKCE

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: UniProt:P24583
data source: Provenance1
name: Protein kinase C, delta type
name: nPKC-delta
name: P24583
name: PRKCD(1-676)
xref: UnificationXref116
feature: FragmentFeature23
cellular location: GO_0005829
comment: Reactome DB_ID: 5611167
display name: PRKCD

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: UniProt:P24583
data source: Provenance1
name: nPKC-theta
name: Protein kinase C, theta type
name: P24583
xref: UnificationXref119
feature: FragmentFeature26
cellular location: GO_0005829
comment: Reactome DB_ID: 5612861
display name: PRKCQ

Protein kinase C, eta type
type: Protein
entity reference: UniProt:P24583
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: PKC-L
name: P24583
name: nPKC-eta
xref: UnificationXref118
feature: FragmentFeature25
cellular location: GO_0005829
comment: Reactome DB_ID: 5614110
display name: PRKCH

UnificationXref910
type: UnificationXref
id: REACT_4595
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4595.1

SequenceSite805
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref911
type: UnificationXref
id: 111844
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111844

SequenceSite804
type: SequenceSite
position status: EQUAL
sequence position: 890

UnificationXref912
type: UnificationXref
id: REACT_3369
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3369.1

SequenceSite807
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref913
type: UnificationXref
id: P39933
db: UniProt

SequenceSite806
type: SequenceSite
position status: EQUAL
sequence position: 433

http://identifiers.org/pubmed/22798961
type: PublicationXref
id: 22798961
author: Wang, Xiaohong
author: Li, Ju-Pi
author: Chuang, Huai-Chia
author: Tan, Tse-Hua
db: Pubmed
title: Regulation of PKC-? function by phosphorylation in T cell receptor signaling
source: Front Immunol 3:197
year: 2012

SequenceSite809
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite808
type: SequenceSite
position status: EQUAL
sequence position: 433

UnificationXref909
type: UnificationXref
id: 111842
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111842

UnificationXref908
type: UnificationXref
id: P46678
db: UniProt

UnificationXref907
type: UnificationXref
id: REACT_3582
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3582.1

UnificationXref906
type: UnificationXref
id: 111841
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111841

SequenceSite802
type: SequenceSite
position status: EQUAL
sequence position: 106

UnificationXref905
type: UnificationXref
id: P29056
db: UniProt

SequenceSite803
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref904
type: UnificationXref
id: REACT_5293
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5293.1

SequenceSite800
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref903
type: UnificationXref
id: 111843
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111843

SequenceSite801
type: SequenceSite
position status: EQUAL
sequence position: 890

AKT1
type: Protein
entity reference: UniProt:P18961
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Protein kinase B
name: RAC-alpha serine/threonine kinase
name: C-AKT
name: P18961
name: PKB alpha
name: RAC-PK-alpha
xref: UnificationXref91
feature: FragmentFeature19
cellular location: GO_0005886
comment: Reactome DB_ID: 5612563
display name: PKB

http://identifiers.org/pubmed/19416660
type: PublicationXref
id: 19416660
author: Ren, M
author: Xu, Y
author: Malhotra, A
author: Schlame, M
db: Pubmed
title: Formation of molecular species of mitochondrial cardiolipin. 1. A novel transacylation mechanism to shuttle fatty acids between sn-1 and sn-2 positions of multiple phospholipid species
source: Biochim Biophys Acta 1791:314-20
year: 2009

AKT1
type: Protein
entity reference: P11792
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Protein kinase B
name: RAC-alpha serine/threonine kinase
name: C-AKT
name: P11792
name: PKB alpha
name: RAC-PK-alpha
xref: UnificationXref92
feature: FragmentFeature20
cellular location: GO_0005886
comment: Reactome DB_ID: 5612564
display name: PKB

Homologues of AKT1
type: Protein
data source: Provenance1
member physical entity: AKT1
xref: UnificationXref93
cellular location: GO_0005886
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5612565

AKT1
type: Protein
entity reference: P12688
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Protein kinase B
name: RAC-alpha serine/threonine kinase
name: C-AKT
name: P12688
name: PKB alpha
name: RAC-PK-alpha
xref: UnificationXref90
feature: FragmentFeature18
cellular location: GO_0005886
comment: Reactome DB_ID: 5612562
display name: PKB

Protein Kinase C, unconventional isoforms
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
member physical entity: Protein kinase C, eta type
xref: UnificationXref120
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5614111
display name: Protein kinase C, novel isoforms

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: UniProt:P24583
data source: Provenance1
name: Protein kinase C, zeta type
name: P24583
name: PKC-zeta
xref: UnificationXref99
feature: FragmentFeature21
cellular location: GO_0005829
comment: Reactome DB_ID: 5614432
display name: PRKCZ

phospho-p-T410-PRKCZ
type: Protein
entity reference: UniProt:P24583
data source: Provenance1
xref: UnificationXref107
feature: FragmentFeature22
feature: ModificationFeature1
cellular location: GO_0005829
comment: Reactome DB_ID: 5614436

3-phosphoinositide dependent protein kinase-1
type: Protein
entity reference: Q12236
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Q12236
name: PDPK1
xref: UnificationXref88
feature: FragmentFeature17
cellular location: GO_0005886
comment: Reactome DB_ID: 5610802
display name: PDK1

3-phosphoinositide dependent protein kinase-1
type: Protein
entity reference: Q03407
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: PDPK1
name: Q03407
xref: UnificationXref87
feature: FragmentFeature16
cellular location: GO_0005886
comment: Reactome DB_ID: 5610798
display name: PDK1

Q03306
type: Protein
entity reference: Q03306
data source: Provenance1
name: 3-phosphoinositide dependent protein kinase-1
name: Note: the coordinates are copied over from Homo sapiens.
name: PDPK1
xref: UnificationXref86
feature: FragmentFeature15
cellular location: GO_0005886
comment: Reactome DB_ID: 5610794
display name: PDK1

UnificationXref901
type: UnificationXref
id: REACT_160231
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160231.1

UnificationXref902
type: UnificationXref
id: P13393
db: UniProt

UnificationXref900
type: UnificationXref
id: 2164816
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2164816

UnificationXref937
type: UnificationXref
id: REACT_4650
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4650.1

UnificationXref936
type: UnificationXref
id: 111832
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111832

UnificationXref939
type: UnificationXref
id: 111833
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111833

UnificationXref938
type: UnificationXref
id: P20434
db: UniProt

AKT1
type: Protein
entity reference: P12688
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Protein kinase B
name: RAC-alpha serine/threonine kinase
name: C-AKT
name: P12688
name: RAC-PK-alpha
xref: UnificationXref76
feature: FragmentFeature12
cellular location: GO_0005829
comment: Reactome DB_ID: 5612553
display name: PKB

AKT1
type: Protein
entity reference: UniProt:P18961
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Protein kinase B
name: RAC-alpha serine/threonine kinase
name: C-AKT
name: P18961
name: RAC-PK-alpha
xref: UnificationXref78
feature: FragmentFeature13
cellular location: GO_0005829
comment: Reactome DB_ID: 5612554
display name: PKB

AKT1
type: Protein
entity reference: P11792
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Protein kinase B
name: RAC-alpha serine/threonine kinase
name: C-AKT
name: P11792
name: RAC-PK-alpha
xref: UnificationXref80
feature: FragmentFeature14
cellular location: GO_0005829
comment: Reactome DB_ID: 5612555
display name: PKB

Homologues of PDPK1
type: Protein
data source: Provenance1
member physical entity: 3-phosphoinositide dependent protein kinase-1
member physical entity: Q03306
xref: UnificationXref89
cellular location: GO_0005886
comment: Reactome DB_ID: 5610803
comment: Converted from EntitySet in Reactome

http://identifiers.org/pubmed/19487573
type: PublicationXref
id: 19487573
author: Agami, Reuven
author: Rouhanifard, Sara H
author: Holland, Eric C
author: Tuschl, Thomas
author: Huse, Jason T
author: Hambardzumyan, Dolores
author: Brennan, Cameron
author: Sohn-Lee, Cherin
author: le Sage, Carlos
author: Wee, Boyoung
author: Pena, John
db: Pubmed
title: The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo
source: Genes Dev. 23:1327-37
year: 2009

Q03306
type: Protein
entity reference: Q03306
data source: Provenance1
name: 3-phosphoinositide dependent protein kinase-1
name: Note: the coordinates are copied over from Homo sapiens.
name: PDPK1
xref: UnificationXref69
feature: FragmentFeature9
cellular location: GO_0005829
comment: Reactome DB_ID: 5612558
display name: PDK1

3-phosphoinositide dependent protein kinase-1
type: Protein
entity reference: Q03407
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: PDPK1
name: Q03407
xref: UnificationXref71
feature: FragmentFeature10
cellular location: GO_0005829
comment: Reactome DB_ID: 5612559
display name: PDK1

3-phosphoinositide dependent protein kinase-1
type: Protein
entity reference: Q12236
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Q12236
name: PDPK1
xref: UnificationXref73
feature: FragmentFeature11
cellular location: GO_0005829
comment: Reactome DB_ID: 5612560
display name: PDK1

Homologues of AKT1
type: Protein
data source: Provenance1
member physical entity: AKT1
xref: UnificationXref81
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5612556

UnificationXref3693
type: UnificationXref
id: 5610483
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610483

http://identifiers.org/pubmed/14660560
type: PublicationXref
id: 14660560
author: Yu, Y
author: Arnold, E
author: Shen, N
author: Ding, Jianping
author: Xu, X
author: Jin, Y
author: Xu, F
author: Jia, J
author: Liu, Y
db: Pubmed
title: Crystal structure of human tryptophanyl-tRNA synthetase catalytic fragment: insights into substrate recognition, tRNA binding, and angiogenesis activity
source: J Biol Chem 279:8378-88
year: 2004

UnificationXref3692
type: UnificationXref
id: 5610481
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610481

Homologues of PDPK1
type: Protein
data source: Provenance1
member physical entity: Q03306
member physical entity: 3-phosphoinositide dependent protein kinase-1
xref: UnificationXref74
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5612561

UnificationXref3695
type: UnificationXref
id: 5610479
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610479

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: ENA5
data source: Provenance1
name: Q12691
name: ATP2B4
name: AT2B4_HUMAN
name: Plasma membrane calcium-transporting ATPase 4
xref: UnificationXref58
feature: FragmentFeature8
cellular location: GO_0005886
comment: Reactome DB_ID: 5614051
display name: PMCA4

UnificationXref3694
type: UnificationXref
id: P33334
db: UniProt

UniProt:P22219
type: ProteinReference
name: VPS15
xref: UnificationXref8293
organism: http://identifiers.org/taxonomy/4932

UnificationXref3697
type: UnificationXref
id: 5610459
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610459

UnificationXref3696
type: UnificationXref
id: P19735
db: UniProt

UnificationXref3699
type: UnificationXref
id: 5610471
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610471

UnificationXref3698
type: UnificationXref
id: P39990
db: UniProt

http://identifiers.org/pubmed/15381398
type: PublicationXref
id: 15381398
author: Jaffe, EK
db: Pubmed
title: The porphobilinogen synthase catalyzed reaction mechanism
source: Bioorg Chem 32:316-25
year: 2004

http://identifiers.org/pubmed/14660569
type: PublicationXref
id: 14660569
author: Chaussade, C
author: Mandel, JL
author: Liaubet, L
author: Payrastre, B
author: Pendaries, C
author: Tronchère, H
author: Laporte, J
author: Pirola, L
db: Pubmed
title: Production of phosphatidylinositol 5-phosphate by the phosphoinositide 3-phosphatase myotubularin in mammalian cells
source: J Biol Chem 279:7304-12
year: 2004

UnificationXref930
type: UnificationXref
id: 111834
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111834

UnificationXref931
type: UnificationXref
id: REACT_2947
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2947.1

UnificationXref932
type: UnificationXref
id: P20436
db: UniProt

UnificationXref933
type: UnificationXref
id: 111835
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111835

UnificationXref934
type: UnificationXref
id: REACT_5521
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5521.1

UnificationXref3691
type: UnificationXref
id: REACT_4663
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4663.1

UnificationXref935
type: UnificationXref
id: P28000
db: UniProt

UnificationXref3690
type: UnificationXref
id: 77464
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=77464

http://identifiers.org/pubmed/7913615
type: PublicationXref
id: 7913615
author: Sheng, H
author: Warner, TD
author: Murad, F
author: Mitchell, JA
db: Pubmed
title: Effects of cyclic GMP on smooth muscle relaxation
source: Adv Pharmacol 26:171-94
year: 1994

UnificationXref928
type: UnificationXref
id: REACT_2777
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2777.1

UnificationXref927
type: UnificationXref
id: 111848
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111848

UnificationXref926
type: UnificationXref
id: REACT_5898
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5898.1

UnificationXref925
type: UnificationXref
id: 111847
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111847

UnificationXref929
type: UnificationXref
id: P20435
db: UniProt

UnificationXref3689
type: UnificationXref
id: 5610482
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610482

UnificationXref3684
type: UnificationXref
id: Q06217
db: UniProt

UnificationXref3683
type: UnificationXref
id: 5610407
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610407

UnificationXref3682
type: UnificationXref
id: P40204
db: UniProt

UnificationXref3681
type: UnificationXref
id: 5610399
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610399

UnificationXref3688
type: UnificationXref
id: 5610423
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610423

UnificationXref3687
type: UnificationXref
id: 5610403
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610403

UnificationXref3686
type: UnificationXref
id: P54999
db: UniProt

UnificationXref3685
type: UnificationXref
id: 5610395
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610395

UnificationXref920
type: UnificationXref
id: REACT_5388
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5388.1

UnificationXref923
type: UnificationXref
id: REACT_5803
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5803.1

UnificationXref3680
type: UnificationXref
id: Q12330
db: UniProt

UnificationXref924
type: UnificationXref
id: P33339
db: UniProt

UnificationXref921
type: UnificationXref
id: P34111
db: UniProt

UnificationXref922
type: UnificationXref
id: 111846
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111846

UniProt:P22202
type: ProteinReference
name: SSA4
xref: UnificationXref4221
organism: http://identifiers.org/taxonomy/4932

VMA4
type: ProteinReference
name: UniProt:P22203
xref: UnificationXref2839
organism: http://identifiers.org/taxonomy/4932

SequenceSite850
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite852
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite851
type: SequenceSite
position status: EQUAL
sequence position: 391

SequenceSite854
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite853
type: SequenceSite
position status: EQUAL
sequence position: 350

UnificationXref958
type: UnificationXref
id: REACT_3012
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3012.1

SequenceSite856
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref959
type: UnificationXref
id: P07703
db: UniProt

SequenceSite855
type: SequenceSite
position status: EQUAL
sequence position: 350

SequenceSite858
type: SequenceSite
position status: EQUAL
sequence position: 1339

SequenceSite857
type: SequenceSite
position status: EQUAL
sequence position: 215

IPP1
type: ProteinReference
name: UniProt:P00817
xref: UnificationXref3870
organism: http://identifiers.org/taxonomy/4932

UnificationXref955
type: UnificationXref
id: REACT_4073
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4073.1

SequenceSite848
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref954
type: UnificationXref
id: 111822
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111822

SequenceSite849
type: SequenceSite
position status: EQUAL
sequence position: 391

UnificationXref957
type: UnificationXref
id: 111823
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111823

UnificationXref956
type: UnificationXref
id: P32349
db: UniProt

UnificationXref951
type: UnificationXref
id: 111831
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111831

UniProt:P00812
type: ProteinReference
name: CAR1
xref: UnificationXref9988
organism: http://identifiers.org/taxonomy/4932

UnificationXref950
type: UnificationXref
id: Q04307
db: UniProt

UnificationXref953
type: UnificationXref
id: P25441
db: UniProt

UnificationXref952
type: UnificationXref
id: REACT_4791
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4791.1

http://identifiers.org/pubmed/7923172
type: PublicationXref
id: 7923172
author: Momparler, RL
author: Laliberte, J
db: Pubmed
title: Human cytidine deaminase: purification of enzyme, cloning, and expression of its complementary DNA
source: Cancer Res 54:5401-7
year: 1994

activated TAK1 mediates p38 MAPK activation
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction42
evidence: Evidence66
xref: UnificationXref1062
xref: RelationshipXref42
xref: UnificationXref1063
pathway order: PathwayStep62
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UniProt:P22217
type: ProteinReference
name: TRX1
xref: UnificationXref2489
organism: http://identifiers.org/taxonomy/4932

UniProt:P22216
type: ProteinReference
name: RAD53
xref: UnificationXref1646
organism: http://identifiers.org/taxonomy/4932

3alpha,7alpha-dihydroxy-5beta-cholest-24-enoyl-CoA
type: SmallMoleculeReference
name: ChEBI:27393 3alpha,7alpha-dihydroxy-5beta-cholest-24-enoyl-CoA
xref: UnificationXref7887

http://identifiers.org/pubmed/20435355
type: PublicationXref
id: 20435355
author: Palczewski, Krzysztof
db: Pubmed
title: Retinoids for treatment of retinal diseases
source: Trends Pharmacol. Sci. 31:284-95
year: 2010

http://identifiers.org/pubmed/8330735
type: PublicationXref
id: 8330735
author: Hernandez, N
db: Pubmed
title: TBP, a universal eukaryotic transcription factor?
source: Genes Dev 7:1291-308
year: 1993

SequenceSite843
type: SequenceSite
position status: EQUAL
sequence position: 1015

SequenceSite842
type: SequenceSite
position status: EQUAL
sequence position: 1

ATP2
type: ProteinReference
name: UniProt:P00830
xref: UnificationXref5156
organism: http://identifiers.org/taxonomy/4932

SequenceSite841
type: SequenceSite
position status: EQUAL
sequence position: 741

SequenceSite840
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref949
type: UnificationXref
id: REACT_3207
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3207.1

SequenceSite847
type: SequenceSite
position status: EQUAL
sequence position: 1401

http://identifiers.org/pubmed/20462400
type: PublicationXref
id: 20462400
author: Henley, Jeremy M
author: Wilkinson, Kevin A
db: Pubmed
title: Mechanisms, regulation and consequences of protein SUMOylation
source: Biochem. J. 428:133-45
year: 2010

SequenceSite846
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref947
type: UnificationXref
id: P22276
db: UniProt

SequenceSite845
type: SequenceSite
position status: EQUAL
sequence position: 1288

UnificationXref948
type: UnificationXref
id: 111821
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111821

SequenceSite844
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref946
type: UnificationXref
id: REACT_2445
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2445.1

SequenceSite839
type: SequenceSite
position status: EQUAL
sequence position: 570

UnificationXref945
type: UnificationXref
id: 111830
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111830

UnificationXref944
type: UnificationXref
id: P47076
db: UniProt

SequenceSite837
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref943
type: UnificationXref
id: REACT_2521
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2521.1

SequenceSite838
type: SequenceSite
position status: EQUAL
sequence position: 741

UnificationXref942
type: UnificationXref
id: 111820
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111820

UnificationXref941
type: UnificationXref
id: P04051
db: UniProt

UnificationXref940
type: UnificationXref
id: REACT_4487
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4487.1

http://identifiers.org/pubmed/8330740
type: PublicationXref
id: 8330740
author: Greider, CW
author: Collins, K
db: Pubmed
title: Tetrahymena telomerase catalyzes nucleolytic cleavage and nonprocessive elongation
source: Genes Dev 7:1364-76
year: 1993

SequenceSite834
type: SequenceSite
position status: EQUAL
sequence position: 1015

SequenceSite833
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite836
type: SequenceSite
position status: EQUAL
sequence position: 1288

SequenceSite835
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite830
type: SequenceSite
position status: EQUAL
sequence position: 1197

SequenceSite832
type: SequenceSite
position status: EQUAL
sequence position: 1401

SequenceSite831
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref973
type: UnificationXref
id: REACT_5519
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5519.1

UnificationXref972
type: UnificationXref
id: 111837
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111837

UnificationXref975
type: UnificationXref
id: 111836
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111836

UnificationXref974
type: UnificationXref
id: P40422
db: UniProt

UnificationXref977
type: UnificationXref
id: 111838
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111838

SequenceSite826
type: SequenceSite
position status: EQUAL
sequence position: 657

UnificationXref976
type: UnificationXref
id: REACT_2999
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2999.1

SequenceSite827
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref979
type: UnificationXref
id: 112452
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112452

SequenceSite828
type: SequenceSite
position status: EQUAL
sequence position: 672

UnificationXref978
type: UnificationXref
id: REACT_4184
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4184.1

SequenceSite829
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref971
type: UnificationXref
id: P22139
db: UniProt

UnificationXref970
type: UnificationXref
id: REACT_3492
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3492.1

2,2'-dilyso diphosphatidyl glycerol
type: SmallMoleculeReference
name: 2,2'-dilyso-1,3-diphosphatidylglycerol
name: 2,2'-dilyso diphosphatidylglycerol
name: 2,2'-dilyso DPG
name: 2,2'-dilysocardiolipin
name: 2,2'-dilyso cardiolipin
name: dilyso cardiolipin
name: 2,2'-dilyso cardiolipin [ChEBI:60431]
xref: UnificationXref8254

SequenceSite825
type: SequenceSite
position status: EQUAL
sequence position: 638

SequenceSite824
type: SequenceSite
position status: EQUAL
sequence position: 497

UnificationXref969
type: UnificationXref
id: 111829
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111829

SequenceSite823
type: SequenceSite
position status: EQUAL
sequence position: 671

3alpha,7alpha,12alpha-trihydroxy-24-oxo-5beta-cholestanoyl-CoA
type: SmallMoleculeReference
name: ChEBI:27379 3alpha,7alpha,12alpha-trihydroxy-24-oxo-5beta-cholestanoyl-CoA
xref: UnificationXref7902

SequenceSite822
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite821
type: SequenceSite
position status: EQUAL
sequence position: 642

SequenceSite820
type: SequenceSite
position status: EQUAL
sequence position: 661

UnificationXref964
type: UnificationXref
id: REACT_3407
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3407.1

UnificationXref963
type: UnificationXref
id: 111826
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111826

UnificationXref962
type: UnificationXref
id: P17890
db: UniProt

SequenceSite819
type: SequenceSite
position status: EQUAL
sequence position: 500

UnificationXref961
type: UnificationXref
id: REACT_2691
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2691.1

UnificationXref968
type: UnificationXref
id: P35718
db: UniProt

SequenceSite817
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref967
type: UnificationXref
id: REACT_4597
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4597.1

SequenceSite818
type: SequenceSite
position status: EQUAL
sequence position: 297

UnificationXref966
type: UnificationXref
id: 111825
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111825

SequenceSite815
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref965
type: UnificationXref
id: P32910
db: UniProt

SequenceSite816
type: SequenceSite
position status: EQUAL
sequence position: 433

http://identifiers.org/pubmed/10648173
type: PublicationXref
id: 10648173
author: Menear, K
author: Baldock, D
author: Graff, P
author: Jones, CE
author: Akhlaq, M
author: Graham, B
db: Pubmed
title: Purification and characterization of human Syk produced using a baculovirus expression system
source: Protein Expr Purif 18:86-94
year: 2000

http://identifiers.org/pubmed/19261456
type: PublicationXref
id: 19261456
author: Procko, E
author: Gaudet, R
db: Pubmed
title: Antigen processing and presentation: TAPping into ABC transporters
source: Curr Opin Immunol 21:84-91
year: 2009

UnificationXref960
type: UnificationXref
id: 111824
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111824

MLCL
type: SmallMoleculeReference
name: lysoDPG
name: Monolysocardiolipin
name: monolyso cardiolipin [ChEBI:60430]
name: monolysoDPG
name: monolyso cardiolipin
xref: UnificationXref8229

Pteroylglutamic acid
type: SmallMoleculeReference
name: Folate
name: Folic acid [ChEBI:5140]
name: Folic acid
xref: UnificationXref6908

di-mu-sulfido-diiron(2+) [ChEBI:33737]
type: SmallMoleculeReference
name: [Fe2S2](2+)
name: [2Fe-2S](2+)
name: di-mu-sulfido-diiron(2+)
name: [Fe2(mu-S)2](2+)
xref: UnificationXref1223

http://identifiers.org/pubmed/9949182
type: PublicationXref
id: 9949182
author: Pébusque, MJ
author: Grégoire, MJ
author: Zhang, B
author: Jonveaux, P
author: Popovici, C
author: Lafage-Pochitaloff, M
author: Birnbaum, D
db: Pubmed
title: The t(6;8)(q27;p11) translocation in a stem cell myeloproliferative disorder fuses a novel gene, FOP, to fibroblast growth factor receptor 1
source: Blood 93:1381-9
year: 1999

[Fe2S2](+)
type: SmallMoleculeReference
name: di-mu-sulfido-diiron(1+)
name: [2Fe-2S](1+)
name: di-mu-sulfido-diiron(1+) [ChEBI:33738]
name: [Fe2(mu-S)2](+)
xref: UnificationXref1236

[Fe2(mu-S)2](0)
type: SmallMoleculeReference
name: di-mu-sulfido-diiron(0) [ChEBI:33739]
name: di-mu-sulfido-diiron(0)
name: 2Fe-2S cluster
name: [Fe2S2](0)
xref: UnificationXref10569

http://identifiers.org/pubmed/18215067
type: PublicationXref
id: 18215067
author: Holmes, RP
author: Murray, MS
author: Lowther, WT
db: Pubmed
title: Active site and loop 4 movements within human glycolate oxidase: implications for substrate specificity and drug design
source: Biochemistry 47:2439-49
year: 2008

http://identifiers.org/pubmed/4358634
type: PublicationXref
id: 4358634
author: Roth, DG
author: Deuel, TF
author: Shelton, E
db: Pubmed
title: Purification and properties of phosphoribosyl pyrophosphate synthetase from rat liver
source: J Biol Chem 249:291-296
year: 1974

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P32364
data source: Provenance1
name: P32364
name: KIF9_HUMAN
name: Kinesin-like protein KIF9
xref: UnificationXref290
feature: FragmentFeature66
cellular location: GO_0005829
comment: Reactome DB_ID: 5615624
display name: KIF9

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P53086
data source: Provenance1
name: P53086
xref: UnificationXref285
feature: FragmentFeature65
cellular location: GO_0005829
comment: Reactome DB_ID: 5615612
display name: KIF18A

P00045
type: Protein
entity reference: P00045
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Cytochrome c
xref: UnificationXref302
feature: FragmentFeature67
cellular location: GO_0005758
comment: Reactome DB_ID: 5611258
display name: CYCS

Homologues of CYCS
type: Protein
data source: Provenance1
member physical entity: P00045
member physical entity: P00044
xref: UnificationXref305
cellular location: GO_0005758
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5611260

Homologues of CYCS
type: Protein
data source: Provenance1
member physical entity: P00044
member physical entity: P00045
xref: UnificationXref308
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5611257

P00044
type: Protein
entity reference: P00044
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Cytochrome c
xref: UnificationXref304
feature: FragmentFeature68
cellular location: GO_0005758
comment: Reactome DB_ID: 5611259
display name: CYCS

P00044
type: Protein
entity reference: P00044
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Cytochrome c
xref: UnificationXref307
feature: FragmentFeature70
cellular location: GO_0005829
comment: Reactome DB_ID: 5611256
display name: CYCS

P00045
type: Protein
entity reference: P00045
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Cytochrome c
xref: UnificationXref306
feature: FragmentFeature69
cellular location: GO_0005829
comment: Reactome DB_ID: 5611252
display name: CYCS

http://identifiers.org/pubmed/11318953
type: PublicationXref
id: 11318953
author: Akakura, K
author: Chairoungdua, A
author: Kim, DK
author: Matsuo, H
author: Cha, SH
author: Fukushima, J
author: Endou, H
author: Goya, T
author: Kanai, Y
author: Mizoguchi, K
author: Awa, Y
author: Shigeta, Y
author: Ito, H
db: Pubmed
title: Human cystinuria-related transporter: localization and functional characterization
source: Kidney Int 59:1821-33
year: 2001

Developmental Biology
type: Pathway
data source: Provenance1
pathway component: Transcriptional regulation of white adipocyte differentiation
pathway component: REACT 239237.1
pathway component: REACT 244034.1
pathway component: REACT 242058.1
evidence: Evidence257
xref: UnificationXref2148
xref: UnificationXref2147
pathway order: PathwayStep244
pathway order: PathwayStep249
pathway order: PathwayStep252
pathway order: PathwayStep241
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P28743
data source: Provenance1
name: P28743
name: CENP-E
xref: UnificationXref280
feature: FragmentFeature64
cellular location: GO_0005829
comment: Reactome DB_ID: 5615618
display name: CENPE

http://identifiers.org/pubmed/9874197
type: PublicationXref
id: 9874197
author: Brees, C
author: Van Veldhoven, PP
author: Fransen, M
author: Baes, M
author: Wylin, T
author: Mannaerts, GP
db: Pubmed
title: Identification and characterization of human PMP34, a protein closely related to the peroxisomal integral membrane protein PMP47 of Candida boidinii
source: Eur J Biochem 258:332-8
year: 1998

endosome membrane
type: CellularLocationVocabulary
xref: UnificationXref250

HMGB1/HMGB2
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref321
cellular location: GO_0005654
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5613308

http://identifiers.org/pubmed/1439791
type: PublicationXref
id: 1439791
author: Cerione, RA
author: Witte, ON
author: Leonard, D
author: Maru, Y
author: Evans, T
author: Hart, MJ
db: Pubmed
title: A GDP dissociation inhibitor that serves as a GTPase inhibitor for the Ras-like protein CDC42Hs
source: Science 258:812-5
year: 1992

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: Q12469
data source: Provenance1
name: PAK-2p34
name: PAK2(213-524)
xref: UnificationXref334
feature: FragmentFeature75
cellular location: GO_0005829
comment: Reactome DB_ID: 5613162
display name: Q12469

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P48562
data source: Provenance1
name: PAK-2p34
name: PAK2(213-524)
xref: UnificationXref332
feature: FragmentFeature74
cellular location: GO_0005829
comment: Reactome DB_ID: 5613161
display name: P48562

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: Q03497
data source: Provenance1
name: PAK-2p34
name: PAK2(213-524)
xref: UnificationXref330
feature: FragmentFeature73
cellular location: GO_0005829
comment: Reactome DB_ID: 5613160
display name: Q03497

Homologues of PAK2(213-524)
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref335
cellular location: GO_0005829
comment: Reactome DB_ID: 5613163
comment: Converted from EntitySet in Reactome

phospho-p-T402-PAK2(213-524)
type: Protein
entity reference: Q12469
data source: Provenance1
xref: UnificationXref338
feature: FragmentFeature78
feature: ModificationFeature5
cellular location: GO_0005829
comment: Reactome DB_ID: 5613169

phospho-p-T402-PAK2(213-524)
type: Protein
entity reference: P48562
data source: Provenance1
xref: UnificationXref337
feature: FragmentFeature77
feature: ModificationFeature4
cellular location: GO_0005829
comment: Reactome DB_ID: 5613167

phospho-p-T402-PAK2(213-524)
type: Protein
entity reference: Q03497
data source: Provenance1
xref: UnificationXref336
feature: FragmentFeature76
feature: ModificationFeature3
cellular location: GO_0005829
comment: Reactome DB_ID: 5613165

Homologues of p-T402-PAK2(213-524)
type: Protein
data source: Provenance1
member physical entity: phospho-p-T402-PAK2(213-524)
xref: UnificationXref339
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5613170

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P11633
data source: Provenance1
name: P11633
xref: UnificationXref320
feature: FragmentFeature72
cellular location: GO_0005654
comment: Reactome DB_ID: 5613307
display name: HMGB2

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P11633
data source: Provenance1
name: P11633
name: High mobility group protein B1
name: Amphoterin
xref: UnificationXref319
feature: FragmentFeature71
cellular location: GO_0005654
comment: Reactome DB_ID: 5613306
display name: HMGB1

http://identifiers.org/pubmed/13679574
type: PublicationXref
id: 13679574
author: Bouvier, M
author: Rousseau, G
author: Angers, S
author: Charest, PG
author: Kohout, T
author: Azzi, M
author: Piñeyro, G
db: Pubmed
title: Beta-arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G protein-coupled receptors
source: Proc Natl Acad Sci U S A 100:11406-11
year: 2003

Dihydrothymine
type: SmallMoleculeReference
name: 5,6-Dihydrothymine
name: 5,6-Dihydrothymine [ChEBI:27468]
name: 5,6-Dihydro-5-methyluracil
xref: UnificationXref9446

http://identifiers.org/pubmed/21903638
type: PublicationXref
id: 21903638
author: De, Antara
db: Pubmed
title: Wnt/Ca2+ signaling pathway: a brief overview
source: Acta Biochim. Biophys. Sin. (Shanghai) 43:745-56
year: 2011

http://identifiers.org/pubmed/14988808
type: PublicationXref
id: 14988808
author: Jakobs, C
author: Huck, JH
author: Verhoeven, NM
author: van der Knaap, MS
author: Struys, EA
author: Salomons, GS
db: Pubmed
title: Ribose-5-phosphate isomerase deficiency: new inborn error in the pentose phosphate pathway associated with a slowly progressive leukoencephalopathy
source: Am J Hum Genet 74:745-51
year: 2004

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: Q03048
data source: Provenance1
name: COF1_HUMAN
name: Cofilin-1
name: Q03048
xref: UnificationXref210
feature: FragmentFeature50
cellular location: GO_0005576
comment: Reactome DB_ID: 5614936
display name: CFL1

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P16474
data source: Provenance1
name: P16474
name: 78 kDa glucose-regulated protein
name: GRP78
name: HSPA5
xref: UnificationXref216
feature: FragmentFeature51
cellular location: GO_0005789
comment: Reactome DB_ID: 5613343
display name: BiP

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P16474
data source: Provenance1
name: P16474
name: 78 kDa glucose-regulated protein
xref: UnificationXref217
feature: FragmentFeature52
cellular location: GO_0005576
comment: Reactome DB_ID: 5613344
display name: HSPA5

http://identifiers.org/pubmed/1550217
type: PublicationXref
id: 1550217
author: Gould, GW
author: Bell, GI
author: Burant, CF
author: Davidson, NO
author: Ifkovits, CA
author: Hausman, AM
author: Buse, JB
db: Pubmed
title: Human intestinal glucose transporter expression and localization of GLUT5
source: Am J Physiol 262:C795-800
year: 1992

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P13517
data source: Provenance1
name: CAPZB_HUMAN
name: P13517
name: F-actin-capping protein subunit beta
xref: UnificationXref228
feature: FragmentFeature53
cellular location: GO_0005829
comment: Reactome DB_ID: 5615205
display name: CAPZB

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: Q03048
data source: Provenance1
name: COF1_HUMAN
name: Cofilin-1
name: Q03048
xref: UnificationXref207
feature: FragmentFeature48
cellular location: GO_0005829
comment: Reactome DB_ID: 5614008
display name: CFL1

Platelet releasate (inferred) cytosolic proteins
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref211
cellular location: GO_0005576
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5614937

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P17555
data source: Provenance1
name: P17555
name: Adenylyl cyclase-associated protein 1
xref: UnificationXref209
feature: FragmentFeature49
cellular location: GO_0005576
comment: Reactome DB_ID: 5614935
display name: CAP1

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P26364
data source: Provenance1
name: GTP:AMP phosphotransferase, mitochondrial
name: P26364
name: Adenylate kinase 3
name: KAD3_HUMAN
xref: UnificationXref247
feature: FragmentFeature55
cellular location: GO_0005759
comment: Reactome DB_ID: 5615646
display name: AK3

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P28495
data source: Provenance1
name: F-actin-capping protein subunit alpha-1
name: P28495
name: CAZA1_HUMAN
xref: UnificationXref230
feature: FragmentFeature54
cellular location: GO_0005829
comment: Reactome DB_ID: 5615201
display name: CAPZA1

alpha-Linolenic acid [ChEBI:10298]
type: SmallMoleculeReference
name: alpha-Linolenic acid
name: Linolenate
name: 9,12,15-Octadecatrienoic acid
name: alpha-Linolenate
xref: UnificationXref8418

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38932
data source: Provenance1
name: Vacuolar protein sorting-associated protein 45
name: P38932
name: VPS45_HUMAN
xref: UnificationXref252
feature: FragmentFeature56
cellular location: endosome membrane
comment: Reactome DB_ID: 5615672
display name: VPS45

http://identifiers.org/pubmed/9883897
type: PublicationXref
id: 9883897
author: Csere, P
author: Lill, R
author: Kispal, G
db: Pubmed
title: Identification of a human mitochondrial ABC transporter, the functional orthologue of yeast Atm1p
source: FEBS Lett 441:266-70
year: 1998

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P19073
data source: Provenance1
name: Cell division control protein 42 homolog
name: P19073
name: CDC42_HUMAN
xref: UnificationXref267
feature: FragmentFeature61
cellular location: GO_0005829
comment: Reactome DB_ID: 5612311
display name: CDC42

Homologues of KIF11
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
member physical entity: P28742
xref: UnificationXref275
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5615606

DOCK-GEFs
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref265
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5615653

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: Q06409
data source: Provenance1
name: Q06409
name: DOCK180
xref: UnificationXref264
feature: FragmentFeature60
cellular location: GO_0005829
comment: Reactome DB_ID: 5615652
display name: DOCK1

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P36017
data source: Provenance1
name: RAB5A_HUMAN
name: P36017
name: Ras-related protein Rab-5A
xref: UnificationXref256
feature: FragmentFeature58
cellular location: endosome membrane
comment: Reactome DB_ID: 5615663
display name: RAB5A

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P32609
data source: Provenance1
name: ZFYVE20
name: Rabenosyn-5
xref: UnificationXref259
feature: FragmentFeature59
cellular location: endosome membrane
comment: Reactome DB_ID: 5615668
display name: P32609

Homologues of RAB5A
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref257
cellular location: endosome membrane
comment: Reactome DB_ID: 5615664
comment: Converted from EntitySet in Reactome

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P36019
data source: Provenance1
name: RAB5A_HUMAN
name: P36019
name: Ras-related protein Rab-5A
xref: UnificationXref254
feature: FragmentFeature57
cellular location: endosome membrane
comment: Reactome DB_ID: 5615659
display name: RAB5A

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P27895
data source: Provenance1
name: KIF11_HUMAN
name: KIF11
name: Kinesin-5
name: P27895
name: Kinesin-like protein KIF11
xref: UnificationXref274
feature: FragmentFeature63
cellular location: GO_0005829
comment: Reactome DB_ID: 5615605
display name: EG5

http://identifiers.org/pubmed/9883880
type: PublicationXref
id: 9883880
author: Callebaut, I
author: Dehoux, P
author: Cossart, P
db: Pubmed
title: EVH1/WH1 domains of VASP and WASP proteins belong to a large family including Ran-binding domains of the RanBP1 family
source: FEBS Lett 441:181-5
year: 1998

P28742
type: Protein
entity reference: P28742
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: KIF11_HUMAN
name: KIF11
name: Kinesin-5
name: Kinesin-like protein KIF11
xref: UnificationXref272
feature: FragmentFeature62
cellular location: GO_0005829
comment: Reactome DB_ID: 5615601
display name: EG5

http://identifiers.org/pubmed/14530973
type: PublicationXref
id: 14530973
author: Mackenzie, B
author: Hediger, MA
db: Pubmed
title: SLC11 family of H+-coupled metal-ion transporters NRAMP1 and DMT1
source: Pflugers Arch 447:571-9
year: 2004

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: UniProt:P24583
data source: Provenance1
name: Protein kinase C, beta type
name: PKC-beta
name: P24583
name: PKC-B
xref: UnificationXref161
feature: FragmentFeature32
cellular location: GO_0005886
comment: Reactome DB_ID: 5611266
display name: PRKCB

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P30619
data source: Provenance1
name: Platelet SEC1 protein
name: P30619
xref: UnificationXref169
feature: FragmentFeature33
cellular location: GO_0005829
comment: Reactome DB_ID: 5611275
display name: STXBP3

phospho-p-STXBP3
type: Protein
entity reference: P30619
data source: Provenance1
xref: UnificationXref171
feature: FragmentFeature34
feature: ModificationFeature2
cellular location: GO_0005829
comment: Reactome DB_ID: 5611277

Homologues of STX4
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref178
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5611288

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P32867
data source: Provenance1
name: P32867
name: Syntaxin 4
xref: UnificationXref175
feature: FragmentFeature35
cellular location: GO_0005829
comment: Reactome DB_ID: 5611283
display name: STX4

Homologues of TUBA4A unfolded
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref187
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5613896

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P39926
data source: Provenance1
name: Syntaxin 4
name: P39926
xref: UnificationXref177
feature: FragmentFeature36
cellular location: GO_0005829
comment: Reactome DB_ID: 5611287
display name: STX4

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P09733
data source: Provenance1
name: TUBA4A unfolded
name: unfolded alpha tubulin -1
xref: UnificationXref186
feature: FragmentFeature38
cellular location: GO_0005829
comment: Reactome DB_ID: 5613895
display name: P09733

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P09734
data source: Provenance1
name: TUBA4A unfolded
name: unfolded alpha tubulin -1
xref: UnificationXref184
feature: FragmentFeature37
cellular location: GO_0005829
comment: Reactome DB_ID: 5613891
display name: P09734

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P46680
data source: Provenance1
name: WD repeat-containing protein 1
name: P46680
name: WDR1_HUMAN
xref: UnificationXref189
feature: FragmentFeature39
cellular location: GO_0005829
comment: Reactome DB_ID: 5614912
display name: WDR1

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P00445
data source: Provenance1
name: P00445
name: Superoxide dismutase (Cu-Zn)
xref: UnificationXref191
feature: FragmentFeature40
cellular location: GO_0005829
comment: Reactome DB_ID: 5614916
display name: SOD1

Q12311
type: Protein
entity reference: NTO1
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Bromodomain and PHD finger-containing protein 3
xref: UnificationXref193
feature: FragmentFeature41
cellular location: GO_0005829
comment: Reactome DB_ID: 5614920
display name: BRPF3

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P09733
data source: Provenance1
name: P09733
name: alpha tubulin -1
xref: UnificationXref196
feature: FragmentFeature43
cellular location: GO_0005576
comment: Reactome DB_ID: 5614923
display name: TUBA4A

Factors involved in megakaryocyte development and platelet production
type: Pathway
data source: Provenance1
pathway component: REACT 189062.3
pathway component: BiochemicalReaction15
pathway component: BiochemicalReaction17
pathway component: BiochemicalReaction16
pathway component: BiochemicalReaction18
evidence: Evidence36
xref: UnificationXref297
xref: UnificationXref296
pathway order: PathwayStep35
pathway order: PathwayStep27
pathway order: PathwayStep29
pathway order: PathwayStep28
pathway order: PathwayStep30
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P46680
data source: Provenance1
name: WD repeat-containing protein 1
name: P46680
name: WDR1_HUMAN
xref: UnificationXref198
feature: FragmentFeature44
cellular location: GO_0005576
comment: Reactome DB_ID: 5614925
display name: WDR1

Homologues of TUBA4A
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref197
cellular location: GO_0005576
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5614924

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P09734
data source: Provenance1
name: P09734
name: alpha tubulin -1
xref: UnificationXref195
feature: FragmentFeature42
cellular location: GO_0005576
comment: Reactome DB_ID: 5614922
display name: TUBA4A

SKI1
type: ProteinReference
name: G1645
name: YGL173C
name: KEM1
name: RAR5
name: UniProt:P22147 XRN1
name: SEP1
name: DST2
name: XRN1
xref: UnificationXref2000
comment: COFACTOR Magnesium. Both strand exchange and nuclease activities require magnesium, for the strand exchange activity, calcium can replace magnesium when the linear ds-DNA has been first resected with an exogenous endonuclease.MISCELLANEOUS Present with 11700 molecules/cell in log phase SD medium.SIMILARITY Belongs to the 5'-3' exonuclease family.
organism: http://identifiers.org/taxonomy/4932

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P17555
data source: Provenance1
name: P17555
name: Adenylyl cyclase-associated protein 1
xref: UnificationXref205
feature: FragmentFeature47
cellular location: GO_0005829
comment: Reactome DB_ID: 5614933
display name: CAP1

http://identifiers.org/pubmed/9331217
type: PublicationXref
id: 9331217
author: Cooper, JA
author: Hart, MC
author: Korshunova, YO
db: Pubmed
title: Vertebrates have conserved capping protein alpha isoforms with specific expression patterns
source: Cell Motil Cytoskeleton 38:120-32
year: 1997

Platelet releasate (inferred) cytosolic proteins
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref208
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5614934

Q12311
type: Protein
entity reference: NTO1
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Bromodomain and PHD finger-containing protein 3
xref: UnificationXref200
feature: FragmentFeature46
cellular location: GO_0005576
comment: Reactome DB_ID: 5614927
display name: BRPF3

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P00445
data source: Provenance1
name: P00445
name: Superoxide dismutase (Cu-Zn)
xref: UnificationXref199
feature: FragmentFeature45
cellular location: GO_0005576
comment: Reactome DB_ID: 5614926
display name: SOD1

Purine salvage
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction857
pathway component: BiochemicalReaction856
pathway component: BiochemicalReaction855
pathway component: BiochemicalReaction854
pathway component: BiochemicalReaction853
pathway component: BiochemicalReaction852
pathway component: BiochemicalReaction851
evidence: Evidence1444
xref: UnificationXref9330
xref: RelationshipXref1113
xref: UnificationXref9331
pathway order: PathwayStep1427
pathway order: PathwayStep1426
pathway order: PathwayStep1425
pathway order: PathwayStep1424
pathway order: PathwayStep1423
pathway order: PathwayStep1422
pathway order: PathwayStep1421
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

PRE1
type: ProteinReference
name: UniProt:P22141
xref: UnificationXref451
organism: http://identifiers.org/taxonomy/4932

EPT1
type: ProteinReference
name: UniProt:P22140
xref: UnificationXref8023
organism: http://identifiers.org/taxonomy/4932

http://identifiers.org/pubmed/21532585
type: PublicationXref
id: 21532585
author: Yokota, Kenichi
author: Meyer, Clifford A
author: Kanno, Jun
author: Imai, Yuuki
author: Baba, Atsushi
author: Igarashi, Katsuhide
author: Ni, Min
author: Okada, Maiko
author: Okuno, Yosuke
author: Brown, Myles
author: Ohtake, Fumiaki
author: Kato, Shigeaki
db: Pubmed
title: PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5B
source: Nat. Cell Biol. 13:668-75
year: 2011

UnificationXref1449
type: UnificationXref
id: 5618645
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618645

UnificationXref1445
type: UnificationXref
id: 5618655
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618655

UnificationXref1446
type: UnificationXref
id: REACT_188905
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_188905.3

UnificationXref1447
type: UnificationXref
id: 5618656
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618656

UnificationXref1448
type: UnificationXref
id: REACT_188909
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_188909.3

UnificationXref1442
type: UnificationXref
id: REACT_187739
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_187739.3

UnificationXref1441
type: UnificationXref
id: 5617014
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617014

UnificationXref1444
type: UnificationXref
id: REACT_188906
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_188906.3

UnificationXref1443
type: UnificationXref
id: 5618654
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618654

UnificationXref1440
type: UnificationXref
id: 5617012
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617012

http://identifiers.org/pubmed/17222083
type: PublicationXref
id: 17222083
author: Lamarche-Vane, N
author: Tcherkezian, J
db: Pubmed
title: Current knowledge of the large RhoGAP family of proteins
source: Biol Cell 99:67-86
year: 2007

3alpha,7alpha,24-Trihydroxy-5beta-cholestanoyl-CoA
type: SmallMoleculeReference
name: 3alpha,7alpha,24-Trihydroxy-5beta-cholestanoyl-CoA [ChEBI:1701]
xref: UnificationXref7897

UnificationXref1458
type: UnificationXref
id: REACT_235254
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_235254.1

UnificationXref1459
type: UnificationXref
id: P24482
db: UniProt

UnificationXref1456
type: UnificationXref
id: REACT_256856
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_256856.1

UnificationXref1457
type: UnificationXref
id: 5617988
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617988

NAM7
type: ProteinReference
name: UniProt:P30771
xref: UnificationXref4152
organism: http://identifiers.org/taxonomy/4932

UnificationXref1455
type: UnificationXref
id: 5617987
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617987

UnificationXref1454
type: UnificationXref
id: REACT_232933
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_232933.1

UnificationXref1453
type: UnificationXref
id: 5607869
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607869

UnificationXref1452
type: UnificationXref
id: 5607868
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607868

UnificationXref1451
type: UnificationXref
id: P09119
db: UniProt

UnificationXref1450
type: UnificationXref
id: REACT_109059
db: Reactome
id version: 4
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_109059.4

http://identifiers.org/pubmed/8647866
type: PublicationXref
id: 8647866
author: Kozasa, T
author: Gilman, AG
db: Pubmed
title: Protein kinase C phosphorylates G12 alpha and inhibits its interaction with G beta gamma
source: J Biol Chem 271:12562-7
year: 1996

GARS dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1049
component: Protein1147
xref: UnificationXref3967
cellular location: GO_0005759
comment: Reactome DB_ID: 5613679

UnificationXref1423
type: UnificationXref
id: 5611796
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611796

KARS dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1050
component: Protein1153
xref: UnificationXref4012
cellular location: GO_0005759
comment: Reactome DB_ID: 5613663

UnificationXref1424
type: UnificationXref
id: 5611797
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611797

SARS2 dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1051
component: Protein1157
xref: UnificationXref4055
cellular location: GO_0005759
comment: Reactome DB_ID: 5613673

UnificationXref1425
type: UnificationXref
id: 5611798
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611798

YARS2 dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1052
component: Protein1160
xref: UnificationXref4084
cellular location: GO_0005759
comment: Reactome DB_ID: 5613587

UnificationXref1426
type: UnificationXref
id: 5611799
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611799

PPA2 dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1054
component: Protein1162
xref: UnificationXref4101
cellular location: GO_0005759
comment: Reactome DB_ID: 5614732

UnificationXref1427
type: UnificationXref
id: 5611844
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611844

Lsm1-7 Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1060
component stoichiometry: Stoichiometry1061
component stoichiometry: Stoichiometry1059
component stoichiometry: Stoichiometry1058
component stoichiometry: Stoichiometry1057
component stoichiometry: Stoichiometry1056
component stoichiometry: Stoichiometry1055
component: Protein1171
component: PhysicalEntity7
component: Protein1170
component: Protein1173
component: Protein1172
component: Protein1169
component: Protein1168
xref: UnificationXref4139
cellular location: GO_0005829
comment: Reactome DB_ID: 5614306

GPI10
type: ProteinReference
name: UniProt:P30777
xref: UnificationXref4642
organism: http://identifiers.org/taxonomy/4932

UnificationXref1428
type: UnificationXref
id: 5617067
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617067

Deadenylated mRNA:Lsm1-7 Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1062
component stoichiometry: Stoichiometry1063
component: PhysicalEntity100
component: Lsm1-7 Complex (name copied from entity in Homo sapiens)
xref: UnificationXref4140
cellular location: GO_0005829
comment: Reactome DB_ID: 5614314

UnificationXref1429
type: UnificationXref
id: 5617069
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617069

Decapped mRNA:LSM1-7 Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1064
component stoichiometry: Stoichiometry1065
component: PhysicalEntity44
component: Lsm1-7 Complex (name copied from entity in Homo sapiens)
xref: UnificationXref4143
cellular location: GO_0005829
comment: Reactome DB_ID: 5614307

SMG1:UPF1:EJC:Translated mRNP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1093
component stoichiometry: Stoichiometry1067
component stoichiometry: Stoichiometry1069
component: Protein1175
component: Translated mRNA Complex with Premature Termination Codon Preceding Exon Junction (name copied from entity in Homo sapiens)
component: SMG1:SMG8:SMG9 Complex (name copied from entity in Homo sapiens)
xref: UnificationXref4175
cellular location: GO_0005829
comment: Reactome DB_ID: 5615433

UnificationXref1420
type: UnificationXref
id: 5611793
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611793

UnificationXref1422
type: UnificationXref
id: 5611795
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611795

UnificationXref1421
type: UnificationXref
id: 5611794
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611794

http://identifiers.org/pubmed/15665109
type: PublicationXref
id: 15665109
author: Dirago, L
author: Mifsud, S
author: Hyland, C
author: Alexander, WS
author: Hilton, DJ
author: Carpinelli, MR
author: Nicola, NA
author: Metcalf, D
db: Pubmed
title: Anomalous megakaryocytopoiesis in mice with mutations in the c-Myb gene
source: Blood 105:3480-7
year: 2005

UnificationXref1436
type: UnificationXref
id: 5617008
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617008

UnificationXref1437
type: UnificationXref
id: 5617011
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617011

UnificationXref1434
type: UnificationXref
id: REACT_188902
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_188902.3

UnificationXref1435
type: UnificationXref
id: Q03018
db: UniProt

UnificationXref1438
type: UnificationXref
id: 5617010
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617010

UnificationXref1439
type: UnificationXref
id: 5617009
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617009

UnificationXref1433
type: UnificationXref
id: 5618658
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618658

UnificationXref1432
type: UnificationXref
id: REACT_188908
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_188908.3

UnificationXref1431
type: UnificationXref
id: 5618657
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618657

UnificationXref1430
type: UnificationXref
id: REACT_187730
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_187730.3

UnificationXref3703
type: UnificationXref
id: 5610455
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610455

Phosphorylated AUF1 p40 Tetramer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1113
component: Protein1184
xref: UnificationXref4210
cellular location: GO_0005829
comment: Reactome DB_ID: 5614787

UnificationXref3702
type: UnificationXref
id: P23394
db: UniProt

AUF1 p37 Tetramer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1112
component: Protein1183
xref: UnificationXref4209
cellular location: GO_0005829
comment: Reactome DB_ID: 5614786

UnificationXref3701
type: UnificationXref
id: 5610463
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610463

UnificationXref3700
type: UnificationXref
id: P36048
db: UniProt

AUF1 Complexed with Translation and Heat Shock Proteins (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1117
component stoichiometry: Stoichiometry1121
component stoichiometry: Stoichiometry1116
component stoichiometry: Stoichiometry1120
component stoichiometry: Stoichiometry1118
component stoichiometry: Stoichiometry1119
component: Protein1190
component: PhysicalEntity7
component: Protein290
component: AUF1 Tetramer: Destabilized mRNA Complex (name copied from entity in Homo sapiens)
component: Protein1185
component: Protein384
xref: UnificationXref4229
cellular location: GO_0005829
comment: Reactome DB_ID: 5614850

UnificationXref3707
type: UnificationXref
id: 5610467
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610467

Phosphorylated AUF1 p40 Dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1110
component: Protein1184
xref: UnificationXref4205
cellular location: GO_0005829
comment: Reactome DB_ID: 5614784

UnificationXref1489
type: UnificationXref
id: 68422
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68422

UnificationXref3706
type: UnificationXref
id: P32639
db: UniProt

AUF1 p37 Dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1109
component: Protein1183
xref: UnificationXref4203
cellular location: GO_0005829
comment: Reactome DB_ID: 5614780

UnificationXref3705
type: UnificationXref
id: 5610475
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610475

AUF1 Tetramer (isoform p37 or p40)
type: Complex
data source: Provenance1
member physical entity: Phosphorylated AUF1 p40 Tetramer (name copied from entity in Homo sapiens)
member physical entity: AUF1 p37 Tetramer (name copied from entity in Homo sapiens)
xref: UnificationXref4211
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5614788

UnificationXref3704
type: UnificationXref
id: P38203
db: UniProt

AUF1 Tetramer: Destabilized mRNA Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1115
component stoichiometry: Stoichiometry1114
component: PhysicalEntity104
component: AUF1 Tetramer (isoform p37 or p40)
xref: UnificationXref4212
cellular location: GO_0005829
comment: Reactome DB_ID: 5614789

mRNA Complex with a Premature Termination Codon Not Preceding an Exon Junction (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1102
component stoichiometry: Stoichiometry1101
component stoichiometry: Stoichiometry1100
component stoichiometry: Stoichiometry1099
component: Protein290
component: Cap Binding Complex (CBC) (name copied from entity in Homo sapiens)
component: PhysicalEntity102
component: Protein384
xref: UnificationXref4184
cellular location: GO_0005829
comment: Reactome DB_ID: 5615404

UnificationXref3709
type: UnificationXref
id: 5610451
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610451

AUF1 Dimer (isoform p37 or p40)
type: Complex
data source: Provenance1
member physical entity: Phosphorylated AUF1 p40 Dimer (name copied from entity in Homo sapiens)
member physical entity: AUF1 p37 Dimer (name copied from entity in Homo sapiens)
xref: UnificationXref4206
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5614785

UnificationXref3708
type: UnificationXref
id: Q06819
db: UniProt

UPF1:eRF3 Complex on Translated mRNA (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1107
component stoichiometry: Stoichiometry1108
component: Translated mRNA Complex with Premature Termination Codon Not Preceding Exon Junction (name copied from entity in Homo sapiens)
component: Protein1175
xref: UnificationXref4186
cellular location: GO_0005829
comment: Reactome DB_ID: 5615406

Evidence595
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/21496649
xref: http://identifiers.org/pubmed/17531985
xref: http://identifiers.org/pubmed/17352659
xref: http://identifiers.org/pubmed/19859661
xref: http://identifiers.org/pubmed/19359157
xref: http://identifiers.org/pubmed/17671086
xref: http://identifiers.org/pubmed/19410547
xref: http://identifiers.org/pubmed/20795950
comment: During normal translation termination eRF3 associates with the ribosome and then interacts with PABP bound to the polyadenylate tail of the mRNA to release the ribosome and allow a new round of translation to commence. Nonsense-mediated decay (NMD) is triggered if eRF3 at the ribosome interacts with UPF1, which may compete with PABP (reviewed in Isken and Maquat 2007, Chang et al. 2007, Behm-Ansmant et al. 2007, Rebbapragada and Lykke-Andersen 2009, Bhuvanagiri et al. 2010, Nicholson et al. 2010, Durand and Lykke-Andersen 2011). An exon junction located 50-55 nt downstream of a termination codon is observed to enhance NMD. Exon-junction complexes (EJCs) are deposited on the mRNA during splicing in the nucleus, remain on mRNAs after transport to the cytosol, and are dislodged by the ribosome as it progresses along the mRNA during the pioneer round of translation (Gehring et al. 2009). EJCs contain the core factors eIF4A-III, Magoh-Y14, and CASC3 as well as the peripheral factors RNPS1, UPF2, and UPF3. UPF2 and UPF3 recruit UPF1 to eRF3 at the terminating ribosome. Thus an EJC downstream of a termination codon will not have been dislodged during translation and will recruit UPF1, triggering NMD. UPF1 is believed to form a complex containing SMG1, SMG8, and SMG9. In the key regulatory step of NMD SMG1 phosphorylates UPF1. The phosphorylated UPF1 then recruits either SMG6 or SMG5 and SMG7. SMG6 is itself an endoribonuclease that cleaves the mRNA. SMG5 and SMG7 do not have endoribonuclease activty, but are thought to recruit ribonucleases. Nonsense-mediated decay has been observed to involve deadenlyation, decapping, and both 5' to 3' and 3' to 5' exonuclease activities, but the exact degradative pathways taken by a given mRNA are not yet known. UPF1 also plays roles in Staufen-mediated decay, histone mRNA decay, telomere maintenance, genome integrity, and may play a role in normal termination of translation.

Evidence596
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18447580
xref: http://identifiers.org/pubmed/21029861
xref: http://identifiers.org/pubmed/18447585
xref: http://identifiers.org/pubmed/18230761
xref: http://identifiers.org/pubmed/18256688
xref: http://identifiers.org/pubmed/16622410
comment: Nonsense-mediated decay of an mRNA can be triggered even if the termination codon does not precede an exon junction (Buhler et al. 2006, Eberle et al. 2008, Silva et al. 2008, Singh et al. 2008, Ivanov et al. 2008). UPF1 and PABP seem to modulate the efficiency of translation termination and PABP in the proximity of a termination codon prevents NMD likely by outcompeting UPF1 for interaction with eRF3 (Singh et al. 2008, Ivanov et al. 2008, Silva et al. 2008). Factors in the competition may be the length and secondary structure of the 3' UTR (Buhler et al. 2006, Eberle et al. 2008). UPF1 preferentially binds some but not all longer UTRs (Hogg and Goff 2010). Interaction of eRF3 with PABP stimulates ribosome dissociation and initiation of a new round of translation on the mRNA. Interaction of eRF3 with UPF1 appears to promote nonsense-mediated decay. It is possible but not yet demonstrated that all components of the SURF complex (SMG1, UPF1, eRF1, eRF3) are assembled on an mRNA without an exon junction complex and that UPF1 is phosphorylated by SMG1.

Evidence593
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17245413
xref: http://identifiers.org/pubmed/15475613
xref: http://identifiers.org/pubmed/14749774
xref: http://identifiers.org/pubmed/16141059
xref: http://identifiers.org/pubmed/11283721
xref: http://identifiers.org/pubmed/19239894
comment: After undergoing rounds of translation, mRNA is normally destroyed by the deadenylation-dependent pathway. Though the trigger is unclear, deadenylation likely proceeds in two steps: one catalyzed by the PAN2-PAN3 complex that shortens the poly(A) tail from about 200 adenosine residues to about 80 residues and one catalyzed by the CCR4-NOT complex or by the PARN enzyme that shortens the tail to about 10-15 residues. After deadenylation the mRNA is then hydrolyzed by either the 5' to 3' pathway or the 3' to 5' pathway. It is unknown what determinants target a mRNA to one pathway or the other. The 5' to 3' pathway is initiated by binding of the Lsm1-7 complex to the 3' oligoadenylate tail followed by decapping by the DCP1-DCP2 complex. The 5' to 3' exoribonuclease XRN1 then hydrolyzes the remaining RNA. The 3' to 5' pathway is initiated by the exosome complex at the 3' end of the mRNA. The exosome processively hydrolyzes the mRNA from 3' to 5', leaving only a capped oligoribonucleotide. The cap is then removed by the scavenging decapping enzyme DCPS.

UnificationXref1480
type: UnificationXref
id: 5618000
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618000

Evidence594
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11331269
xref: http://identifiers.org/pubmed/14636577
xref: http://identifiers.org/pubmed/19359157
xref: http://identifiers.org/pubmed/16452507
xref: http://identifiers.org/pubmed/11544179
xref: http://identifiers.org/pubmed/20817927
xref: http://identifiers.org/pubmed/19417104
comment: SMG1 phosphorylates UPF1 in vitro and in vivo (Denning et al. 2001, Yamashita et al. 2001, Kashima et al. 2006). Serines 1073, 1078, 1096, and 1116 in isoform 2 (Serines 1084, 1089, 1107, 1127 in isoform 1) are phosphorylated in vitro and phosphorylation at serines 1078 and 1096 has been confirmed in vivo (Yamashita et al. 2001, Ohnishi et al. 2003, Kashima et al. 2006). UPF1 also contains additional serine and threonine residues that could be phosphorylated. SMG8 and SMG9 associate with SMG1 and regulate the kinase activity of SMG1 (Yamashita et al. 2009). The phosphorylation reaction is rate-limiting in nonsense-mediated decay and is therefore regarded as a licensing step (reviewed in Rebbapragada and Lykke-Andersen 2009). Phosphorylation is enhanced by the exon junction complex, which can interact with UPF1 via UPF2 and/or UPF3 (Kashima et al. 2006, Ivanov et al. 2008) or via Y14:Magoh (Ivanov et al. 2008). SMG8 and SMG9 bind SMG1 and regulate its kinase activity (Yamashita et al. 2009, Fernandez et al. 2011).

Evidence591
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12515382
xref: http://identifiers.org/pubmed/17245413
xref: http://identifiers.org/pubmed/15475613
xref: http://identifiers.org/pubmed/14749774
xref: http://identifiers.org/pubmed/16141059
xref: http://identifiers.org/pubmed/16299471
xref: http://identifiers.org/pubmed/11283721
xref: http://identifiers.org/pubmed/19239894
comment: The XRN1 exoribonuclease hydrolyzes decapped mRNA from 5' to 3' and yields ribonucleotides having 5'-monophosphates. In yeast Xrn1 associates with the Lsm1-7 complex.

Evidence592
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/20584987
xref: http://identifiers.org/pubmed/17245413
xref: http://identifiers.org/pubmed/15475613
xref: http://identifiers.org/pubmed/14749774
xref: http://identifiers.org/pubmed/16141059
xref: http://identifiers.org/pubmed/11283721
xref: http://identifiers.org/pubmed/19239894
comment: Degradation of mRNA from 5' to 3' occurs in three steps. First, the mRNA is bound at its 3' end by the Lsm1-7 complex. The bound Lsm1-7 may prevent nucleases from accessing the 3' end. Second, the 7-methylguanosine cap of the mRNA is hydrolyzed by the DCP1-DCP2 complex. Third, the 5' end of the decapped mRNA is attacked by the XRN1 exoribonuclease which digests the remainder of the mRNA from 5' to 3'. These processes may be physically connected by PATL1, the homolog of yeast Pat1, which stably binds the Lsm1-7 complex and interacts with the DCP1-DCP2 decapping complex and the Ccr4-NOT deadenylation complex (Ozgur et al. 2010).

Evidence590
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17245413
xref: http://identifiers.org/pubmed/15475613
xref: http://identifiers.org/pubmed/16051491
xref: http://identifiers.org/pubmed/14749774
xref: http://identifiers.org/pubmed/16141059
xref: http://identifiers.org/pubmed/11283721
xref: http://identifiers.org/pubmed/15711010
xref: http://identifiers.org/pubmed/15231747
xref: http://identifiers.org/pubmed/19279404
xref: http://identifiers.org/pubmed/19239894
comment: The Lsm1-7 complex forms a heptameric ring that binds the 3' oligoadenylated ends of mRNAs that have been deadenylated. The bound Lsm1-7 may prevent access of the exosome (a 3' to 5' exonuclease) to the 3' end and thereby direct the mRNA to the 5' to 3' exonuclease pathway. The yeast Lsm1-7 complex has a preference for oligoadenylated RNA compared to polyadenylated RNA, however other determinants of binding by Lsm1-7 are unknown.

UnificationXref11096
type: UnificationXref
id: 5618136
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618136

UnificationXref1485
type: UnificationXref
id: REACT_240037
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_240037.1

http://identifiers.org/pubmed/224930
type: PublicationXref
id: 224930
author: Inoue, K
author: Yamasawa, K
author: Nishimukai, H
db: Pubmed
title: Purification and partial characterization of aldehyde dehydrogenase from human erythrocytes.
source: Biochim Biophys Acta 569:117-23
year: 1979

UnificationXref11095
type: UnificationXref
id: REACT_203093
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_203093.2

UnificationXref1486
type: UnificationXref
id: 5617994
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617994

UnificationXref11098
type: UnificationXref
id: 727753
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=727753

UnificationXref1487
type: UnificationXref
id: REACT_231197
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_231197.1

UnificationXref11097
type: UnificationXref
id: REACT_244559
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_244559.1

UnificationXref1488
type: UnificationXref
id: 5607895
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607895

UnificationXref1481
type: UnificationXref
id: REACT_252076
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_252076.1

Evidence599
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15364901
xref: http://identifiers.org/pubmed/17099701
xref: http://identifiers.org/pubmed/17057362
xref: http://identifiers.org/pubmed/15372072
xref: http://identifiers.org/pubmed/15525708
comment: Transcription of miRNA genes. Most miRNAs are transcribed by RNA polymerase II. The miRNAs may be autonomous transcription units or they may be located in other transcripts, including locations within introns and other untranslated regions. Of the polymerase II transcribed miRNAs, about 60% are located in introns of protein coding genes, 12 % are in introns of non-coding RNAs, 18% are in exons of non-coding RNAs, and 10% uncertain. A second class of miRNA genes are associated with Alu and other repetitive elements and are cotranscribed with these elements by RNA polymerase III. There are currently only a few proven examples of polymerase III transcribed miRNAs.

http://identifiers.org/pubmed/18436705
type: PublicationXref
id: 18436705
author: Scheuner, D
author: Kaufman, RJ
db: Pubmed
title: The unfolded protein response: a pathway that links insulin demand with beta-cell failure and diabetes
source: Endocr Rev 29:317-33
year: 2008

UnificationXref11099
type: UnificationXref
id: REACT_23184
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_23184.2

UnificationXref1482
type: UnificationXref
id: 5617989
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617989

UnificationXref1483
type: UnificationXref
id: REACT_254556
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_254556.1

Evidence597
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17531985
xref: http://identifiers.org/pubmed/17352659
xref: http://identifiers.org/pubmed/19859661
xref: http://identifiers.org/pubmed/19359157
xref: http://identifiers.org/pubmed/18447580
xref: http://identifiers.org/pubmed/17671086
xref: http://identifiers.org/pubmed/18447585
xref: http://identifiers.org/pubmed/18256688
xref: http://identifiers.org/pubmed/20795950
comment: Nonsense-mediated decay has been observed with mRNAs that do not have an exon junction complex (EJC) downstream of the termination codon (reviewed in Isken and Maquat 2007, Chang et al. 2007, Behm-Ansmant et al. 2007, Rebbapragada and Lykke-Andersen 2009, Nicholson et al. 2010). In these cases the trigger is unknown but a correlation with the length of the 3' UTR has sometimes been seen. The current model posits a competition between PABP and UPF1 for access to eRF3 at the terminating ribosome (Ivanov et al. 2008, Singh et al. 2008, reviewed in Bhuvanagiri et al. 2010). Abnormally long 3' UTRs may prevent PABP from efficiently interacting with eRF3 and allow UPF1 to bind eRF3 instead. Long UTRs with hairpin loops may bring PABP closer to eRF3 and help evade NMD (Eberle et al. 2008). The pathway of degradation taken during EJC-independent NMD has not been elucidated. It is thought that phosphorylation of UPF1 by SMG1 and recruitment of SMG6 or SMG5 and SMG7 are involved, as with EJC-enhanced NMD, but this has not yet been shown.

UnificationXref1484
type: UnificationXref
id: 5617990
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617990

Evidence598
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/21496649
xref: http://identifiers.org/pubmed/17531985
xref: http://identifiers.org/pubmed/17352659
xref: http://identifiers.org/pubmed/19859661
xref: http://identifiers.org/pubmed/19359157
xref: http://identifiers.org/pubmed/17671086
xref: http://identifiers.org/pubmed/19010255
xref: http://identifiers.org/pubmed/18524595
xref: http://identifiers.org/pubmed/20795950
comment: The Nonsense-Mediated Decay (NMD) pathway activates the destruction of mRNAs containing premature termination codons (PTCs) (reviewed in Isken and Maquat 2007, Chang et al. 2007, Behm-Ansmant et al. 2007, Neu-Yilik and Kulozik 2008, Rebbapragada and Lykke-Andersen 2009, Bhuvanagiri et al. 2010, Nicholson et al. 2010, Durand and Lykke-Andersen 2011). In mammalian cells a termination codon can be recognized as premature if it precedes an exon-exon junction by at least 50-55 nucleotides or if it is followed by an abnormal 3' untranslated region (UTR). While length of the UTR may play a part, the qualifications for being "abnormal" have not been fully elucidated. Also, some termination codons preceding exon junctions are not degraded by NMD so the criteria for triggering NMD are not yet fully known (reviewed in Rebbapragada and Lykke-Andersen 2009). While about 30% of disease-associated mutations in humans activate NMD, about 10% of normal human transcripts are also degraded by NMD (reviewed in Stalder and Muhlemann 2008, Neu-Yilik and Kulozik 2008, Bhuvanagiri et al. 2010, Nicholson et al. 2010). Thus NMD is a normal physiological process controlling mRNA stability in unmutated cells. Exon junction complexes (EJCs) are deposited on an mRNA during splicing in the nucleus and are displaced by ribosomes during the first round of translation. When a ribosome terminates translation the A site encounters the termination codon and the eRF1 factor enters the empty A site and recruits eRF3. Normally, eRF1 cleaves the translated polypeptide from the tRNA in the P site and eRF3 interacts with Polyadenylate-binding protein (PABP) bound to the polyadenylated tail of the mRNA. During activation of NMD eRF3 interacts with UPF1 which is contained in a complex with SMG1, SMG8, and SMG9. NMD can arbitrarily be divided into EJC-enhanced and EJC-independent pathways. In EJC-enhanced NMD, an exon junction is located downstream of the PTC and the EJC remains on the mRNA after termination of…

UnificationXref3712
type: UnificationXref
id: P49955
db: UniProt

Translated mRNA Complex with Premature Termination Codon Not Preceding Exon Junction (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1098
component stoichiometry: Stoichiometry1106
component stoichiometry: Stoichiometry1105
component stoichiometry: Stoichiometry1104
component stoichiometry: Stoichiometry1103
component: GDP bound eRF3 (name copied from entity in Homo sapiens)
component: 80S ribosome (name copied from entity in Homo sapiens)
component: Protein1176
component: SmallMolecule72
component: mRNA Complex with a Premature Termination Codon Not Preceding an Exon Junction (name copied from entity in Homo sapiens)
xref: UnificationXref4185
cellular location: GO_0005829
comment: Reactome DB_ID: 5615405

UnificationXref3711
type: UnificationXref
id: 5610484
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610484

SMG1:Phosphorylated UPF1:EJC:Translated mRNP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1097
component stoichiometry: Stoichiometry1095
component stoichiometry: Stoichiometry1096
component: Protein1182
component: Translated mRNA Complex with Premature Termination Codon Preceding Exon Junction (name copied from entity in Homo sapiens)
component: SMG1:SMG8:SMG9 Complex (name copied from entity in Homo sapiens)
xref: UnificationXref4177
cellular location: GO_0005829
comment: Reactome DB_ID: 5615434

UnificationXref3714
type: UnificationXref
id: Q99181
db: UniProt

GDP bound eRF3 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1091
component stoichiometry: Stoichiometry1090
component: Protein1181
component: SmallMolecule67
xref: UnificationXref4173
cellular location: GO_0005829
comment: Reactome DB_ID: 5611317

UnificationXref3713
type: UnificationXref
id: 5610432
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610432

80S ribosome (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1087
component stoichiometry: Stoichiometry1088
component: Complex19
component: Complex29
xref: UnificationXref4170
cellular location: GO_0005829
comment: Reactome DB_ID: 5609872

UnificationXref3716
type: UnificationXref
id: Q02554
db: UniProt

Cap Binding Complex (CBC) (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1080
component stoichiometry: Stoichiometry1081
component: Protein1179
component: Protein1180
xref: UnificationXref4166
cellular location: GO_0005829
comment: Reactome DB_ID: 5615403

UnificationXref3715
type: UnificationXref
id: 5610444
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610444

mRNA Complex with a Premature Termination Codon Preceding an Exon Junction (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1084
component stoichiometry: Stoichiometry1085
component stoichiometry: Stoichiometry1082
component stoichiometry: Stoichiometry1083
component: Protein290
component: Cap Binding Complex (CBC) (name copied from entity in Homo sapiens)
component: PhysicalEntity101
component: Protein384
xref: UnificationXref4169
cellular location: GO_0005829
comment: Reactome DB_ID: 5615413

UnificationXref3718
type: UnificationXref
id: Q04693
db: UniProt

Magoh-Y14 complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1072
component: PhysicalEntity7
xref: UnificationXref4157
cellular location: GO_0005829
comment: Reactome DB_ID: 5615418

UnificationXref3717
type: UnificationXref
id: 5610436
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610436

Core Exon Junction Complex (Core EJC) (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1075
component stoichiometry: Stoichiometry1073
component stoichiometry: Stoichiometry1074
component: PhysicalEntity7
component: Protein1177
component: Magoh-Y14 complex (name copied from entity in Homo sapiens)
xref: UnificationXref4160
cellular location: GO_0005829
comment: Reactome DB_ID: 5615419

Exon Junction:UPF2:UPF3 Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1076
component stoichiometry: Stoichiometry1077
component stoichiometry: Stoichiometry1078
component: PhysicalEntity7
component: Core Exon Junction Complex (Core EJC) (name copied from entity in Homo sapiens)
component: Protein1178
xref: UnificationXref4163
cellular location: GO_0005829
comment: Reactome DB_ID: 5615424

Glycerophospholipid biosynthesis
type: Pathway
data source: Provenance1
pathway component: REACT 188992.3
pathway component: REACT 189003.3
pathway component: REACT 188994.3
pathway component: REACT 189024.3
pathway component: REACT 188974.3
pathway component: REACT 188995.3
pathway component: REACT 191569.3
pathway component: REACT 189009.3
pathway component: REACT 189324.3
pathway component: REACT 188999.3
pathway component: REACT 188998.3
pathway component: REACT 188993.3
pathway component: REACT 189002.3
pathway component: REACT 188997.3
pathway component: REACT 189000.3
evidence: Evidence1274
xref: UnificationXref8261
xref: RelationshipXref929
xref: UnificationXref8262
pathway order: PathwayStep1250
pathway order: PathwayStep1257
pathway order: PathwayStep1248
pathway order: PathwayStep1230
pathway order: PathwayStep1221
pathway order: PathwayStep1232
pathway order: PathwayStep1245
pathway order: PathwayStep1207
pathway order: PathwayStep1235
pathway order: PathwayStep1216
pathway order: PathwayStep1219
pathway order: PathwayStep1241
pathway order: PathwayStep1238
pathway order: PathwayStep1227
pathway order: PathwayStep1210
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref3719
type: UnificationXref
id: 5610440
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610440

Translated mRNA Complex with Premature Termination Codon Preceding Exon Junction (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1071
component stoichiometry: Stoichiometry1086
component stoichiometry: Stoichiometry1070
component stoichiometry: Stoichiometry1092
component stoichiometry: Stoichiometry1079
component stoichiometry: Stoichiometry1089
component: GDP bound eRF3 (name copied from entity in Homo sapiens)
component: 80S ribosome (name copied from entity in Homo sapiens)
component: mRNA Complex with a Premature Termination Codon Preceding an Exon Junction (name copied from entity in Homo sapiens)
component: Protein1176
component: Exon Junction:UPF2:UPF3 Complex (name copied from entity in Homo sapiens)
component: SmallMolecule72
xref: UnificationXref4174
cellular location: GO_0005829
comment: Reactome DB_ID: 5615425

Alcohol catabolism
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction987
pathway component: BiochemicalReaction988
pathway component: BiochemicalReaction989
evidence: Evidence1611
xref: UnificationXref10415
xref: UnificationXref10414
xref: RelationshipXref1335
pathway order: PathwayStep1592
pathway order: PathwayStep1593
pathway order: PathwayStep1594
display name: Ethanol oxidation
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref1490
type: UnificationXref
id: REACT_3288
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3288.1

Evidence582
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10828066
comment: WARS2 (mitochondrial tryptophanyl tRNA synthetase) catalyzes the reaction of tryptophan, mitochondrial tRNA(Trp), and ATP to form Trp-tRNA(Trp), AMP, and pyrophosphate. The enzyme is a class I tRNA synthetase (Jorgensen et al. 2000).

http://identifiers.org/pubmed/8647822
type: PublicationXref
id: 8647822
author: Sanchez, HB
author: Osborne, TF
author: Rosenfeld, JM
author: Vallett, SM
db: Pubmed
title: A direct role for sterol regulatory element binding protein in activation of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene
source: J Biol Chem 271:12247-53
year: 1996

UnificationXref1491
type: UnificationXref
id: 5607896
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607896

Evidence583
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15779907
comment: YARS2 (mitochondrial tyrosyl tRNA synthetase) catalyzes the reaction of tyrosine, mitochondrial tRNA(Tyr), and ATP to form Tyr-tRNA(Tyr), AMP, and pyrophosphate. The enzyme, a class I tRNA synthetase, is a homodimer (Bonnefond et al. 2005).

Evidence584
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15779907
comment: VARS2 (mitochondrial valyl tRNA synthetase) catalyzes the reaction of valine, mitochondrial tRNA(val), and ATP to form Val-tRNA(Val), AMP, and pyrophosphate. The VARS2 gene has been identified by computational analysis of the human genome sequence; its function has been inferred from those of the biochemically characterized mitochondrial aspartyl and tyrosyl tRNA synthetases (Bonnefond et al. 2005).

Evidence585
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16300924
comment: Mitochondrial PPA2 (pyrophosphatase (inorganic) 2) catalyzes the hydrolysis of pyrophosphate to yield two molecules of orthophosphate. The enzyme requires Mg++ for activity (Curbo et al. 2006). The enzyme is inferred to be a homodimer by analogy to its cytosolic isoform.

Evidence580
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10764807
comment: SARS2 (mitochondrial seryl tRNA synthetase) catalyzes the reaction of serine, mitochondrial tRNA(Ser), and ATP to form Ser-tRNA(Ser), AMP, and pyrophosphate. SARS2 is a class II tRNA synthetase inferred from the biochemical properties of its bovine homologue to function as a dimer (Yokogawa et al. 2000).

Evidence581
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15779907
comment: TARS2 (mitochondrial threonyl tRNA synthetase) catalyzes the reaction of threonine, mitochondrial tRNA(Thr), and ATP to form Thr-tRNA(Thr), AMP, and pyrophosphate. The TARS2 gene has been identified by computational analysis of the human genome sequence; its function has been inferred from those of the biochemically characterized mitochondrial aspartyl and tyrosyl tRNA synthetases (Bonnefond et al. 2005).

UnificationXref1498
type: UnificationXref
id: 29892
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29892

UnificationXref1499
type: UnificationXref
id: REACT_4670
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4670.1

UnificationXref1496
type: UnificationXref
id: REACT_2773
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2773.1

UnificationXref1497
type: UnificationXref
id: CHEBI:16497
db: ChEBI

UnificationXref1494
type: UnificationXref
id: CHEBI:18077
db: ChEBI

Evidence586
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11121736
comment: Mitochondrial tRNA synthetases act in the mitochondrial matrix to catalyze the reactions of tRNAs encoded in the mitochondrial genome, their cognate amino acids, and ATP to form aminoacyl-tRNAs, AMP, and pyrophosphate (Schneider et al. 2000). The synthetase enzymes that catalyze these reactions are all encoded in the nuclear genome. In three cases, glycine, lysine, and glutamine, a single gene encodes two enzyme isoforms, one cytosolic and one mitochondrial. All other mitochondrial tRNA synthetases are encoded by genes different from the ones encoding the corresponding cytosolic enzymes.

UnificationXref1495
type: UnificationXref
id: 30187
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=30187

Evidence587
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16125937
xref: http://identifiers.org/pubmed/764868
xref: http://identifiers.org/pubmed/18682559
xref: http://identifiers.org/pubmed/5324172
xref: http://identifiers.org/pubmed/5324173
xref: http://identifiers.org/pubmed/18767960
xref: http://identifiers.org/pubmed/1894595
xref: http://identifiers.org/pubmed/182209
comment: tRNA synthetases catalyze the ligation of tRNAs to their cognate amino acids in an ATP-dependent manner. The reaction proceeds in two steps. First, amino acid and ATP form an aminoacyl adenylate molecule, releasing pyrophosphate. The aminoacyl adenylate remains associated with the synthetase enzyme where, in the second step it reacts with tRNA to form aminoacyl tRNA and AMP. The rapid hydrolysis of pyrophosphate makes these reactions essentially irreversible under physiological conditions (Fersht and Kaethner 1976a). Specificity of the tRNA charging reactions is achieved both by specific recognition of amino acid and tRNA substrates by the synthetase, and by an editing process in which incorrect aminoacyl adenylate molecules (e.g., valyl adenylate associated with isoleucyl tRNA synthetase) are hydrolyzed rather than conjugated to tRNAs in the second step of the reaction (Baldwin and Berg 1966a,b; Fersht and Kaethner 1976b). The tRNA synthetases can be divided into two structural classes based on conserved amino acid sequence features (Burnbaum and Schimmel 1991). A single synthetase mediates the charging of all of the tRNA species specific for any one amino acid but, with three exceptions, glycine, lysine, and glutamine, the synthetase that catalyzes aminoacylation of mitochondrial tRNAs is encoded by a different gene than the one that acts on mitochondrial tRNAs. Both mitochondrial and cytosolic tRNA synthetase enzymes are encoded by genes in the nuclear genome. A number of tRNA synthetases are known to have functions distinct from tRNA charging (reviewed by Park et al. 2005). Additionally, mutations in several of the tRNA synthetases, often affecting protein domains that are dispensable in vitro for aminoacyl tRNA synthesis, are associated with a diverse array of neurological and other diseases (Antonellis and Green 2008; Park et al. 2008). These findings raise interest into the role of these enzymes in human development and disease.

UnificationXref1492
type: UnificationXref
id: 5607898
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607898

Evidence588
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17245413
xref: http://identifiers.org/pubmed/18441014
xref: http://identifiers.org/pubmed/15769464
xref: http://identifiers.org/pubmed/15475613
xref: http://identifiers.org/pubmed/15068804
xref: http://identifiers.org/pubmed/14749774
xref: http://identifiers.org/pubmed/16141059
xref: http://identifiers.org/pubmed/11283721
xref: http://identifiers.org/pubmed/15273322
xref: http://identifiers.org/pubmed/19239894
comment: The scavenging nuclease DCPS hydrolyzes the triphosphate bond between the 7-methylguanosine cap and the remaining oligoribonucleotide body of the mRNA. The products are 7-methylguanosine 5'-monophosphate and an oligoribonucleotide with a 5'-diphosphate.

SMG1:SMG8:SMG9 Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1068
component: PhysicalEntity7
xref: UnificationXref4154
cellular location: GO_0005829
comment: Reactome DB_ID: 5615432

UnificationXref1493
type: UnificationXref
id: REACT_243487
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_243487.1

UnificationXref3710
type: UnificationXref
id: 5610480
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610480

Evidence589
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17245413
xref: http://identifiers.org/pubmed/15475613
xref: http://identifiers.org/pubmed/14749774
xref: http://identifiers.org/pubmed/16141059
xref: http://identifiers.org/pubmed/11283721
xref: http://identifiers.org/pubmed/19239894
comment: The degradation of mRNA from 3' to 5' occurs in two steps. First, the exosome exoribonuclease complex binds the 3' end of the oligoadenylated mRNA and hydrolyzes it from 3' to 5', yielding ribonucleotides having 5'-monophosphates, until a capped oligoribonucleotide remains. Second, the scavenging decapping enzyme DCPS hydrolyzes the 7-methylguanosine cap.

UnificationXref11080
type: UnificationXref
id: REACT_17455
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_17455.2

UnificationXref1468
type: UnificationXref
id: 5607882
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607882

40S:Met-tRNAi:mRNA (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1169
component stoichiometry: Stoichiometry1167
component stoichiometry: Stoichiometry1168
component: PhysicalEntity8
component: PhysicalEntity110
component: Complex29
xref: UnificationXref4338
cellular location: GO_0005829
comment: Reactome DB_ID: 5609488

UnificationXref11081
type: UnificationXref
id: 5615129
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615129

UnificationXref1467
type: UnificationXref
id: P10363
db: UniProt

80S:Met-tRNAi:mRNA (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1164
component stoichiometry: Stoichiometry1165
component stoichiometry: Stoichiometry1166
component: PhysicalEntity8
component: 80S ribosome (name copied from entity in Homo sapiens)
component: PhysicalEntity110
xref: UnificationXref4335
cellular location: GO_0005829
comment: Reactome DB_ID: 5609880

UnificationXref11082
type: UnificationXref
id: 380873
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=380873

eIF2:GDP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1175
component stoichiometry: Stoichiometry1176
component: SmallMolecule67
component: Complex27
xref: UnificationXref4354
cellular location: GO_0005829
comment: Reactome DB_ID: 5609489

UnificationXref11083
type: UnificationXref
id: REACT_15849
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15849.2

UnificationXref1469
type: UnificationXref
id: P13382
db: UniProt

eIF2B subunits complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1174
component stoichiometry: Stoichiometry1172
component stoichiometry: Stoichiometry1173
component stoichiometry: Stoichiometry1170
component stoichiometry: Stoichiometry1171
component: Protein1210
component: Protein1209
component: Protein1213
component: Protein1211
component: Protein1212
xref: UnificationXref4353
cellular location: GO_0005829
comment: Reactome DB_ID: 5609520

L-glutamic acid removal
type: SequenceModificationVocabulary
xref: UnificationXref5965

eIF2:GDP: eIF2B (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1178
component stoichiometry: Stoichiometry1179
component stoichiometry: Stoichiometry1177
component: eIF2B subunits complex (name copied from entity in Homo sapiens)
component: SmallMolecule67
component: Complex27
xref: UnificationXref4355
cellular location: GO_0005829
comment: Reactome DB_ID: 5609521

L-arginine removal
type: SequenceModificationVocabulary
xref: UnificationXref6027

eIF4F:mRNP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1150
component stoichiometry: Stoichiometry1151
component: mRNP (name copied from entity in Homo sapiens)
component: Complex22
xref: UnificationXref4313
cellular location: GO_0005829
comment: Reactome DB_ID: 5609495

80S:Met-tRNAi:mRNA:eIF5B:GTP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1161
component stoichiometry: Stoichiometry1160
component stoichiometry: Stoichiometry1158
component stoichiometry: Stoichiometry1159
component: PhysicalEntity8
component: 80S ribosome (name copied from entity in Homo sapiens)
component: PhysicalEntity110
component: eIF5B:GTP (name copied from entity in Homo sapiens)
xref: UnificationXref4333
cellular location: GO_0005829
comment: Reactome DB_ID: 5609878

48S complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1152
component stoichiometry: Stoichiometry1153
component stoichiometry: Stoichiometry1154
component stoichiometry: Stoichiometry1155
component: PhysicalEntity7
component: Complex24
component: Complex22
component: PhysicalEntity110
xref: UnificationXref4318
cellular location: GO_0005829
comment: Reactome DB_ID: 5609483

eIF5B:GDP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1162
component stoichiometry: Stoichiometry1163
component: Protein1208
component: SmallMolecule67
xref: UnificationXref4334
cellular location: GO_0005829
comment: Reactome DB_ID: 5609879

eIF5B:GTP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1156
component stoichiometry: Stoichiometry1157
component: Protein1208
component: SmallMolecule26
xref: UnificationXref4332
cellular location: GO_0005829
comment: Reactome DB_ID: 5609877

UnificationXref11078
type: UnificationXref
id: CHEBI:18357
db: ChEBI

UnificationXref11077
type: UnificationXref
id: REACT_17550
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_17550.2

UnificationXref1460
type: UnificationXref
id: 5607891
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607891

UnificationXref1461
type: UnificationXref
id: P21951
db: UniProt

UnificationXref11079
type: UnificationXref
id: 209789
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=209789

UnificationXref1462
type: UnificationXref
id: 5607887
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607887

UnificationXref11074
type: UnificationXref
id: REACT_17509
db: Reactome
id version: 4
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_17509.4

UnificationXref1463
type: UnificationXref
id: 5607892
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607892

UnificationXref11073
type: UnificationXref
id: 209914
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=209914

UnificationXref1464
type: UnificationXref
id: 68419
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68419

UnificationXref11076
type: UnificationXref
id: 209794
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=209794

UnificationXref1465
type: UnificationXref
id: REACT_3087
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3087.1

UnificationXref11075
type: UnificationXref
id: CHEBI:28918
db: ChEBI

UnificationXref1466
type: UnificationXref
id: 5607893
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607893

UnificationXref11093
type: UnificationXref
id: REACT_206034
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_206034.2

HuR with Unknown Phosphorylation: mRNA Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1143
component stoichiometry: Stoichiometry1144
component: Protein1202
component: PhysicalEntity109
xref: UnificationXref4286
cellular location: GO_0005654
comment: Reactome DB_ID: 5614814

UnificationXref11094
type: UnificationXref
id: 5615132
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615132

HuR with phosphoserine221 and phosphoserine318:mRNA Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1141
component stoichiometry: Stoichiometry1142
component: PhysicalEntity108
component: Protein1205
xref: UnificationXref4281
cellular location: GO_0005654
comment: Reactome DB_ID: 5615007

UnificationXref11091
type: UnificationXref
id: 5615130
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615130

UnificationXref1479
type: UnificationXref
id: REACT_253916
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_253916.1

HuR with phosphoserine221 and phosphoserine158:mRNA Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1139
component stoichiometry: Stoichiometry1140
component: PhysicalEntity107
component: Protein1203
xref: UnificationXref4276
cellular location: GO_0005654
comment: Reactome DB_ID: 5615005

http://identifiers.org/pubmed/22983114
type: PublicationXref
id: 22983114
author: Boutros, Michael
author: Bartscherer, Kerstin
author: Chaudhary, Varun
author: Gross, Julia Christina
db: Pubmed
title: Active Wnt proteins are secreted on exosomes
source: Nat. Cell Biol. 14:1036-45
year: 2012

UnificationXref11092
type: UnificationXref
id: 5615150
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615150

UnificationXref1478
type: UnificationXref
id: 5608139
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608139

TTP:mRNA Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1133
component stoichiometry: Stoichiometry1132
component stoichiometry: Stoichiometry1134
component: Protein1200
component: Protein1201
component: PhysicalEntity106
xref: UnificationXref4259
cellular location: GO_0005829
comment: Reactome DB_ID: 5614774

UnificationXref11090
type: UnificationXref
id: 5615128
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615128

mRNP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1148
component stoichiometry: Stoichiometry1149
component: PhysicalEntity111
component: PhysicalEntity110
xref: UnificationXref4312
cellular location: GO_0005829
comment: Reactome DB_ID: 5609494

40S:eIF3:eIF1A (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1145
component stoichiometry: Stoichiometry1146
component stoichiometry: Stoichiometry1147
component: Protein295
component: Complex28
component: Complex29
xref: UnificationXref4302
cellular location: GO_0005829
comment: Reactome DB_ID: 5609884

Phosphorylated BRF1 (Ser92, Ser203):mRNA Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1130
component stoichiometry: Stoichiometry1129
component: Protein1199
component: PhysicalEntity105
xref: UnificationXref4249
cellular location: GO_0005829
comment: Reactome DB_ID: 5614807

BRF1:mRNA Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1127
component stoichiometry: Stoichiometry1126
component: Protein1198
component: PhysicalEntity105
xref: UnificationXref4245
cellular location: GO_0005829
comment: Reactome DB_ID: 5614799

Ubiquitinated AUF1 Tetramer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1123
component: Protein1195
xref: UnificationXref4233
cellular location: GO_0005829
comment: Reactome DB_ID: 5614795

Ubiquitinated AUF1 Tetramer: Destabilized mRNA Complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry1125
component stoichiometry: Stoichiometry1124
component: PhysicalEntity104
component: Ubiquitinated AUF1 Tetramer (name copied from entity in Homo sapiens)
xref: UnificationXref4234
cellular location: GO_0005829
comment: Reactome DB_ID: 5614796

UnificationXref1472
type: UnificationXref
id: 5607877
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607877

UnificationXref1473
type: UnificationXref
id: 5607878
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607878

http://identifiers.org/pubmed/6693436
type: PublicationXref
id: 6693436
author: Hu, SZ
author: Wang, TS
author: Korn, D
db: Pubmed
title: DNA primase from KB cells. Characterization of a primase activity tightly associated with immunoaffinity-purified DNA polymerase-alpha.
source: J Biol Chem 259:1854-65
year: 1984

UnificationXref11089
type: UnificationXref
id: REACT_5252
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5252.3

UnificationXref1470
type: UnificationXref
id: 5607873
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607873

UnificationXref11088
type: UnificationXref
id: 114523
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=114523

UnificationXref1471
type: UnificationXref
id: P38121
db: UniProt

UnificationXref11087
type: UnificationXref
id: REACT_15723
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15723.2

UnificationXref1476
type: UnificationXref
id: 5607899
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607899

UnificationXref11086
type: UnificationXref
id: 374935
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374935

UnificationXref1477
type: UnificationXref
id: REACT_256775
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_256775.1

UnificationXref11085
type: UnificationXref
id: REACT_23148
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_23148.2

UnificationXref1474
type: UnificationXref
id: 5607883
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607883

UnificationXref11084
type: UnificationXref
id: 549254
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=549254

UnificationXref1475
type: UnificationXref
id: 5607894
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607894

Evidence442
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/7954831
xref: http://identifiers.org/pubmed/12101119
xref: http://identifiers.org/pubmed/9857026
xref: http://identifiers.org/pubmed/10559246
xref: http://identifiers.org/pubmed/9308960
xref: http://identifiers.org/pubmed/16212495
xref: http://identifiers.org/pubmed/7478592
xref: http://identifiers.org/pubmed/8810315
xref: http://identifiers.org/pubmed/8276860
xref: http://identifiers.org/pubmed/8969170
comment: Guanine nucleotide exchange factors (GEFs) activate GTPases by enhancing the exchange of bound GDP for GTP. Much evidence points to GEFs being critical mediators of Rho GTPase activation (Schmidt and Hall, 2002). Many GEFs are known to be highly specific for a particular GTPase, e.g. Fgd1/Cdc42 and p115RhoGEF/Rho (Hart et al., 1996, Zheng et al., 1996). Others have a broader spectrum and activate several GTPases, e.g. Vav1 for Rac, Rho, and Cdc42 (Hart et al, 1994).

UnificationXref897
type: UnificationXref
id: REACT_2572
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2572.1

Evidence441
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18721752
xref: http://identifiers.org/pubmed/17463226
xref: http://identifiers.org/pubmed/10744726
xref: http://identifiers.org/pubmed/1706616
xref: http://identifiers.org/pubmed/12807903
xref: http://identifiers.org/pubmed/11679632
xref: http://identifiers.org/pubmed/16912174
xref: http://identifiers.org/pubmed/7565730
xref: http://identifiers.org/pubmed/16978839
xref: http://identifiers.org/pubmed/10867024
xref: http://identifiers.org/pubmed/10722704
xref: http://identifiers.org/pubmed/12869563
xref: http://identifiers.org/pubmed/18653779
xref: http://identifiers.org/pubmed/19193720
xref: http://identifiers.org/pubmed/17018285
xref: http://identifiers.org/pubmed/15534001
xref: http://identifiers.org/pubmed/16061658
xref: http://identifiers.org/pubmed/16778220
xref: http://identifiers.org/pubmed/9168115
xref: http://identifiers.org/pubmed/9135143
xref: http://identifiers.org/pubmed/8665853
xref: http://identifiers.org/pubmed/9556621
xref: http://identifiers.org/pubmed/17545517
xref: http://identifiers.org/pubmed/19047365
xref: http://identifiers.org/pubmed/7929212
xref: http://identifiers.org/pubmed/9275162
xref: http://identifiers.org/pubmed/15023535
xref: http://identifiers.org/pubmed/8617750
xref: http://identifiers.org/pubmed/16914727
comment: ERBB4, also known as HER4, belongs to the ERBB family of receptors, which also includes ERBB1 (EGFR i.e. HER1), ERBB2 (HER2 i.e. NEU) and ERBB3 (HER3). Similar to EGFR, ERBB4 has an extracellular ligand binding domain, a single transmembrane domain and a cytoplasmic domain which contains an active tyrosine kinase and a C-tail with multiple phosphorylation sites. At least three and possibly four splicing isoforms of ERBB4 exist that differ in their C-tail and/or the extracellular juxtamembrane regions: ERBB4 JM-A CYT1, ERBB4 JM-A CYT2 and ERBB4 JM-B CYT1 (the existence of ERBB4 JM-B CYT2 has not been confirmed). ERBB4 becomes activated by binding one of its seven ligands, three of which, HB-EGF, epiregulin EPR and betacellulin BTC, are EGF-like (Elenius et al. 1997, Riese et al. 1998), while four, NRG1, NRG2, NRG3 and NRG4, belong to the neuregulin family (Tzahar et al. 1994, Carraway et al. 1997, Zhang et al. 1997, Hayes et al. 2007). Upon ligand binding, ERBB4 forms homodimers (Sweeney et al. 2000) or it heterodimerizes with ERBB2 (Li et al. 2007). Dimers of ERBB4 undergo trans-autophosphorylation on tyrosine residues in the C-tail (Cohen et al. 1996, Kaushansky et al. 2008, Hazan et al. 1990, Li et al. 2007), triggering downstream signaling cascades. The pathway Signaling by ERBB4 only shows signaling by ERBB4 homodimers. Signaling by heterodimers of ERBB4 and ERBB2 is shown in the pathway Signaling by ERBB2. Ligand-stimulated ERBB4 is also able to form heterodimers with ligand-stimulated EGFR (Cohen et al. 1996) and ligand-stimulated ERBB3 (Riese et al. 1995). Dimers of ERBB4 with EGFR and dimers of ERBB4 with ERBB3 were demonstrated in mouse cell lines in which human ERBB4 and EGFR or ERBB3 were exogenously expressed. These heterodimers undergo trans-autophosphorylation, but their downstream signaling and physiological significance have not been studied. All splicing isoforms of ERBB4 possess two tyrosine residues in the C-tail that serve as docking sites for SH…

UnificationXref898
type: UnificationXref
id: 2167818
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2167818

Evidence440
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: The CYT1 isoforms of ERBB4 possess a C-tail tyrosine residue that, upon trans-autophosphorylation, serves as a docking site for the p85 alpha subunit of PI3K - PIK3R1 (Kaushansky et al. 2008, Cohen et al. 1996). Binding of PIK3R1 to CYT1 isoforms of ERBB4 is followed by recruitment of the p110 catalytic subunit of PI3K (PIK3CA), leading to assembly of an active PI3K complex that converts PIP2 to PIP3 and activates AKT signaling (Kainulainen et al. 2000).

UnificationXref895
type: UnificationXref
id: CHEBI:16526
db: ChEBI

UnificationXref896
type: UnificationXref
id: 29376
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29376

http://identifiers.org/pubmed/12800216
type: PublicationXref
id: 12800216
author: Zhang, M
author: Zhu, F
db: Pubmed
title: DNA polymerase zeta: new insight into eukaryotic mutagenesis and mammalian embryonic development.
source: World J Gastroenterol 9:1165-9
year: 2003

UnificationXref899
type: UnificationXref
id: REACT_160592
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160592.1

UniProt:Q00578
type: ProteinReference
name: SSL2
xref: UnificationXref3366
organism: http://identifiers.org/taxonomy/4932

Evidence449
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9278091
xref: http://identifiers.org/pubmed/3113327
comment: The classical signalling mechanism for G alpha (i) is inhibition of the cAMP dependent pathway through inhibition of adenylate cyclase. Decreased production of cAMP from ATP results in decreased activity of cAMP-dependent protein kinases.

UnificationXref890
type: UnificationXref
id: 2164813
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2164813

Evidence448
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/7937899
comment: When a ligand activates a G protein-coupled receptor, it induces a conformational change in the receptor (a change in shape) that allows the receptor to function as a guanine nucleotide exchange factor (GEF), stimulating the exchange of GDP for GTP on the G alpha subunit. In the traditional view of heterotrimeric protein activation, this exchange triggers the dissociation of the now active G alpha subunit from the beta:gamma dimer, initiating downstream signalling events. The G alpha subunit has intrinsic GTPase activity and will eventually hydrolyze the attached GTP to GDP, allowing reassociation with G beta:gamma. Additional GTPase-activating proteins (GAPs) stimulate the GTPase activity of G alpha, leading to more rapid termination of the transduced signal. In some cases the downstream effector may have GAP activity, helping to deactivate the pathway. This is the case for phospholipase C beta, which possesses GAP activity within its C-terminal region.

Evidence447
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12101119
xref: http://identifiers.org/pubmed/16757309
xref: http://identifiers.org/pubmed/10445846
xref: http://identifiers.org/pubmed/14521508
xref: http://identifiers.org/pubmed/16212495
xref: http://identifiers.org/pubmed/12618308
xref: http://identifiers.org/pubmed/15630019
comment: The Rho family of small guanine nucleotide binding proteins is one of five generally recognized branches of the Ras superfamily. Like most Ras superfamily members, typical Rho proteins function as binary switches controlling a variety of biological processes. They perform this function by cycling between active GTP-bound and inactive GDP-bound conformations. Mammalian Rho GTPases include RhoA, RhoB and RhoC (Rho proteins), Rac1 3 (Rac proteins), Cdc42, TC10, TCL, Wrch1, Chp/Wrch2, RhoD and RhoG, to name some. The family also includes RhoH and Rnd1-3, which lack GTPase activity and are predicted to exist in a constitutively active state. Members of the Rho family have been identified in all eukaryotes. Including the atypical RHOBTB1-3 and RHOT1-2 proteins, 24 Rho family members have been identified in mammals (Jaffe and Hall, 2005; Bernards, 2005; Ridley, 2006). Among Rho GTPases, RhoA, Rac1 and Cdc42 have been most extensively studied. These proteins are best known for their ability to induce dynamic rearrangements of the plasma membrane-associated actin cytoskeleton (Aspenstrom et al, 2004; Murphy et al, 1999; Govek et al, 2005). Beyond this function, Rho GTPases also regulate actomyosin contractility and microtubule dynamics. Rho mediated effects on transcription and membrane trafficking are believed to be secondary to these functions. At the more macroscopic level, Rho GTPases have been implicated in many important cell biological processes, including cell growth control, cytokinesis, cell motility, cell cell and cell extracellular matrix adhesion, cell transformation and invasion, and development (Govek et al., 2005). The illustration below lists Rho GTPase effectors implicated in actin and microtubule dynamics (courtesy: Govek et al., 2005, Genes and Development, CSHL Press). Detailed annotations of various biological processes regulated by Rho GTPases will be available in future releases.

Evidence446
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9308960
xref: http://identifiers.org/pubmed/17222083
xref: http://identifiers.org/pubmed/16212495
comment: The cycling of Rho GTPases is tightly controlled by three classes of protein. These are (1) guanine nucleotide dissociation inhibitors or GDIs, which maintain Rho proteins in an inactive state in the cytoplasm, (2) guanine nucleotide exchange factors or GEFs, which destabilize the interaction between Rho proteins and their bound nucleotide, the net result of which is the exchange of bound GDP for the more abundant GTP, and (3) GTPase Activating Proteins or GAPs, which stimulate the low intrinsic GTP hydrolysis activity of Rho family members, thus promoting their inactivation. GDIs, GEFs, and GAPs are themselves subject to tight regulation, and the overall level of Rho activity reflects the balance of their activities. In their active GTP-bound state, Rho family members have the ability to interact with a large variety of so-called effector proteins. By changing the subcellular localization of effectors, by altering their enzymatic properties, or by directing the formation of specific effector complexes, members of the Rho family mediate their various effects. This Rho GTPase cycle is diagrammed in the figure below. External or internal cues promote the release of Rho GTPases from the inhibitory complex (1) which allows them to associate with the plasma membrane (2) where they are activated by GEFs (3) and can signal to effector proteins. Then, GAPs inactivate the GTPases by accelerating the intrinsic GTPase activity, leading to the GDP bound form (4). Once again, the GDI molecules stabilize the inactive GDP bound form in the cytoplasm, waiting for further instructions (5). (Figure and text from Tcherkezian and Lamarche Vane, 2007).

UnificationXref893
type: UnificationXref
id: 2164809
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2164809

UnificationXref3732
type: UnificationXref
id: REACT_242204
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_242204.1

Evidence445
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10676816
xref: http://identifiers.org/pubmed/15921909
xref: http://identifiers.org/pubmed/10655614
xref: http://identifiers.org/pubmed/12471028
xref: http://identifiers.org/pubmed/9194563
comment: GDIs sequester the inactive GTPases, preventing the dissociation of GDP and interactions with regulatory and effector molecules. They maintain Rho GTPases as soluble cytosolic proteins by forming high affinity complexes. In these complexes, the geranylgeranyl membrane targeting moiety present at the C terminus of the Rho GTPases is shielded from the solvent by its insertion into the hydrophobic pocket formed by the immunoglobulin like beta sandwich of the GDI (DerMardirossian and Bokoch, 2005). Rho proteins, when released from the sequestering cytosolic GDIs, insert into the lipid bilayer of the plasma membrane with their isoprenylated C termini. The membrane bound GEFs activate these free RhoGTPases and thereby trigger the downstream signaling events via respective effector proteins on the membrane (Robbe et al., 2003). Detailed annotation of the activities of farnesyltransferase / geranylgeranyltransferases on prenylation of Rho GTPases thereby enabling their subsequent localization to plasma membrane will be available in future releases.

UnificationXref894
type: UnificationXref
id: REACT_160713
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160713.1

UnificationXref3731
type: UnificationXref
id: 5610488
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610488

Evidence444
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/7824266
xref: http://identifiers.org/pubmed/10676816
xref: http://identifiers.org/pubmed/7543319
xref: http://identifiers.org/pubmed/10433515
xref: http://identifiers.org/pubmed/9113980
xref: http://identifiers.org/pubmed/15292224
xref: http://identifiers.org/pubmed/15921909
xref: http://identifiers.org/pubmed/16190977
xref: http://identifiers.org/pubmed/10655614
xref: http://identifiers.org/pubmed/1439791
xref: http://identifiers.org/pubmed/9194563
comment: GDP dissociation inhibitors or GDIs confer an additional but important layer of Rho GTPase regulation along with GEFs and GAPs. GDIs mainly inhibit the dissociation of bound guanine nucleotide (usually GDP) from their partner GTPases. So far, three human GDIs with proven biological functions have been found: RhoGDI/GDIalpha/GDI1, hematopoietic cell selective Ly/D4GDI/GDIbeta/GDI2, and Rho GDIgamma/GDI3 (DerMardirossian and Bokoch, 2005). Three specific biochemical functions of GDIs have been established: inhibiting the dissociation of GDP from Rho proteins, maintaining the GTPases in an inactive form, and preventing GTPase activation by GEFs (Olofsson, 1999). Detailed annotations of GDIs will be available in future releases.

UnificationXref891
type: UnificationXref
id: REACT_160071
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160071.1

UnificationXref3730
type: UnificationXref
id: 5610485
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610485

Evidence443
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/2825022
xref: http://identifiers.org/pubmed/8288572
xref: http://identifiers.org/pubmed/11804589
xref: http://identifiers.org/pubmed/12015138
xref: http://identifiers.org/pubmed/9605766
xref: http://identifiers.org/pubmed/17222083
xref: http://identifiers.org/pubmed/11431473
comment: The human genome includes approximately 70 genes that are predicted to encode Rho-specific GTPase Activating Proteins (RhoGAPs). As in the case of GEFs, some RhoGAPs are believed to be highly specific, whereas others are more promiscuous with respect to their target GTPases. Increasing evidence suggests that GAPs are also regulated by external cues in addition to being signal terminators leading to Rho GTPase inactivation. These proteins play important role in many Rho mediated signaling pathways. Some known GAPs include p190 A, cdGAP, ARAP3, MgcRacGAP, Chimaerin, Nadrin, TCGAP, DLC 1, 2, ArhGAP6, Myosin IXA. These and other GAPs have been implicated in many processes, such as exocytosis, endocytosis, cytokinesis, cell differentiation, migration, neuronal morphogenesis, angiogenesis and tumor suppression. Detailed annotations of the biological role of GAPs in Rho mediated signaling will be available in future releases.

UnificationXref892
type: UnificationXref
id: CHEBI:16835
db: ChEBI

SequenceSite992
type: SequenceSite
position status: EQUAL
sequence position: 317

UnificationXref3735
type: UnificationXref
id: REACT_206297
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_206297.2

SequenceSite993
type: SequenceSite
position status: EQUAL
sequence position: 345

UnificationXref3736
type: UnificationXref
id: 5610489
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610489

SequenceSite990
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref3733
type: UnificationXref
id: 5610486
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610486

SequenceSite991
type: SequenceSite
position status: EQUAL
sequence position: 476

UnificationXref3734
type: UnificationXref
id: 5610487
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610487

eRF3-GTP:eRF1:peptidyl-tRNA:mRNA:80S Ribosome Complex
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry530
component stoichiometry: Stoichiometry529
component stoichiometry: Stoichiometry528
component: peptidyl-tRNA:mRNA:80S Ribosome Complex
component: Protein673
component: GTP bound eRF3
xref: UnificationXref2023
xref: UnificationXref2022
cellular location: GO_0005829
comment: Reactome DB_ID: 141670

UnificationXref3739
type: UnificationXref
id: REACT_2708
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2708.1

eRF3-GDP:eRF1:peptidyl-tRNA:mRNA:80S Ribosome Complex
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry531
component stoichiometry: Stoichiometry534
component stoichiometry: Stoichiometry535
component: GDP bound eRF3
component: peptidyl-tRNA:mRNA:80S Ribosome Complex
component: Protein673
xref: UnificationXref2028
xref: UnificationXref2029
cellular location: GO_0005829
comment: Reactome DB_ID: 141688

GDP bound eRF3
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry532
component stoichiometry: Stoichiometry533
component: SmallMolecule67
component: Protein672
xref: UnificationXref2027
xref: UnificationXref2026
cellular location: GO_0005829
comment: Reactome DB_ID: 141699

UnificationXref3737
type: UnificationXref
id: REACT_206520
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_206520.2

eRF3-GDP:eRF1:tRNA:mRNA:80S Ribosome Complex
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry540
component stoichiometry: Stoichiometry541
component stoichiometry: Stoichiometry536
component: GDP bound eRF3
component: Protein673
component: tRNA:mRNA:80S Ribosome Complex
xref: UnificationXref2040
xref: UnificationXref2039
cellular location: GO_0005829
comment: Reactome DB_ID: 141697

UnificationXref3738
type: UnificationXref
id: 72156
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=72156

RFC Heteropentamer:RNA primer-DNA primer:G-strand extended telomere end duplex:PCNA homotrimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry516
component stoichiometry: Stoichiometry515
component: Complex98
component: RFC Heteropentamer:RNA primer-DNA primer:G-strand extended telomere end (name copied from entity in Homo sapiens)
xref: UnificationXref1944
cellular location: GO_0005654
comment: Reactome DB_ID: 5611940

SEC59
type: ProteinReference
name: UniProt:P20048
xref: UnificationXref4703
organism: http://identifiers.org/taxonomy/4932

RNA primer-DNA primer:G-strand extended telomere:PCNA (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry520
component stoichiometry: Stoichiometry519
component stoichiometry: Stoichiometry518
component stoichiometry: Stoichiometry517
component: PhysicalEntity29
component: SmallMolecule63
component: PhysicalEntity30
component: Complex98
xref: UnificationXref1947
cellular location: GO_0005654
comment: Reactome DB_ID: 5611942

peptidyl-tRNA:mRNA:80S Ribosome Complex
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry524
component stoichiometry: Stoichiometry525
component stoichiometry: Stoichiometry523
component: PhysicalEntity46
component: PhysicalEntity45
component: SmallMolecule71
xref: UnificationXref2012
xref: UnificationXref2013
cellular location: GO_0005829
comment: Reactome DB_ID: 141668

SequenceSite998
type: SequenceSite
position status: EQUAL
sequence position: 3056

http://identifiers.org/pubmed/2408761
type: PublicationXref
id: 2408761
author: Sharp, PA
author: Moore, CL
db: Pubmed
title: Accurate cleavage and polyadenylation of exogenous RNA substrate.
source: Cell 41:845-55
year: 1985

GTP bound eRF3
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry527
component stoichiometry: Stoichiometry526
component: Protein672
component: SmallMolecule26
xref: UnificationXref2017
xref: UnificationXref2018
cellular location: GO_0005829
comment: Reactome DB_ID: 141685

SequenceSite999
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite996
type: SequenceSite
position status: EQUAL
sequence position: 1981

SequenceSite997
type: SequenceSite
position status: EQUAL
sequence position: 1

RNA primer-DNA primer:G-strand extended telomere (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry510
component stoichiometry: Stoichiometry509
component: RNA primer:G-strand extended telomere end:DNA polymerase alpha:primase complex (name copied from entity in Homo sapiens)
component: PhysicalEntity30
xref: UnificationXref1936
cellular location: GO_0005654
comment: Reactome DB_ID: 5611937

SequenceSite994
type: SequenceSite
position status: EQUAL
sequence position: 1

RFC Heteropentamer:RNA primer-DNA primer:G-strand extended telomere end (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry511
component stoichiometry: Stoichiometry512
component stoichiometry: Stoichiometry513
component stoichiometry: Stoichiometry514
component: PhysicalEntity29
component: SmallMolecule63
component: PhysicalEntity30
component: Complex96
xref: UnificationXref1941
cellular location: GO_0005654
comment: Reactome DB_ID: 5611939

SequenceSite995
type: SequenceSite
position status: EQUAL
sequence position: 476

Evidence451
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: When a ligand activates a G protein-coupled receptor, it induces a conformational change in the receptor (a change in shape) that allows the receptor to function as a guanine nucleotide exchange factor (GEF), stimulating the exchange of GDP for GTP on the G alpha subunit. In the traditional view of heterotrimeric protein activation, this exchange triggers the dissociation of the now active G alpha subunit from the beta:gamma dimer, initiating downstream signalling events. The G alpha subunit has intrinsic GTPase activity and will eventually hydrolyze the attached GTP to GDP, allowing reassociation with G beta:gamma. Additional GTPase-activating proteins (GAPs) stimulate the GTPase activity of G alpha, leading to more rapid termination of the transduced signal. In some cases the downstream effector may have GAP activity, helping to deactivate the pathway. This is the case for phospholipase C beta, which possesses GAP activity within its C-terminal region.

UnificationXref884
type: UnificationXref
id: 2164818
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2164818

Evidence450
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/1939224
xref: http://identifiers.org/pubmed/8647866
xref: http://identifiers.org/pubmed/2502548
xref: http://identifiers.org/pubmed/8429024
comment: G alpha z (Lounsbury et al. 1991) and G alpha 12 (Kozasa & Gilman, 1996) are excellent in vitro substrates for all three subtypes of protein kinase C (PKC). Activation of PKC in intact platelets by agents such as thrombin, thromboxane A2 (TXA2) analogues and phorbol esters leads to rapid and near-stoichiometric phosphorylation of G alpha z (Carlson et al. 1989). The primary site of G alpha z phosphorylation is Ser-27 (Lounsbury et al. 1993). This phosphorylation blocks the interaction of G alpha z with Gbeta:gamma suggesting that it is a regulatory mechanism for attenuating signalling by preventing subunit reassociation.

UnificationXref885
type: UnificationXref
id: REACT_161409
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_161409.1

Evidence453
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16102047
xref: http://identifiers.org/pubmed/19212139
xref: http://identifiers.org/pubmed/9296496
comment: The classic signalling route for G alpha (q) is activation of phospholipase C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and protein kinase C activation. This provides a path to calcium-regulated kinases and phosphatases, GEFs, MAP kinase cassettes and other proteins that mediate cellular responses ranging from granule secretion, integrin activation, and aggregation in platelets. Gq participates in many other signalling events including direct interaction with RhoGEFs that stimulate RhoA activity and inhibition of PI3K. Both in vitro and in vivo, the G-protein Gq seems to be the predominant mediator of the activation of platelets.

UnificationXref886
type: UnificationXref
id: 113563
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113563

Evidence452
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/1908722
xref: http://identifiers.org/pubmed/11313909
xref: http://identifiers.org/pubmed/10954748
xref: http://identifiers.org/pubmed/9032437
xref: http://identifiers.org/pubmed/2491850
comment: The heterotrimeric G protein Gz, is a member of the Gi family. Unlike other Gi family members it lacks an ADP ribosylation site cysteine four residues from the carboxyl terminus and is thus pertussis toxin-insensitive. It inhibits adenylyl cyclase types I, V and VI. G alpha (z) interacts with the Rap1 GTPase activating protein (Rap1GAP) to attenuate Rap1 signaling. Like all G-proteins Gz has an intrinsic GTPase activity, but this activity tends to be lower for the pertussis toxin insensitive G-proteins, most strikingly so for Gz, whose kcat value for GTP hydrolysis is 200-fold lower than those of Gs or Gi (Grazziano et al. 1989). Gz knockout mice have disrupted platelet aggregation at physiological concentrations of epinephrine and responses to several neuroactive drugs are altered (Yang et al. 2000).

UnificationXref887
type: UnificationXref
id: REACT_5783
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5783.1

UnificationXref888
type: UnificationXref
id: 2167853
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2167853

UnificationXref889
type: UnificationXref
id: REACT_160628
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160628.1

Evidence459
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/7937899
xref: http://identifiers.org/pubmed/8073283
comment: Slow intrisinc GTPase activity results in an inactivation of the alpha-i subunit by hydrolyzing GTP to GDP.

Evidence458
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18240029
xref: http://identifiers.org/pubmed/12040175
xref: http://identifiers.org/pubmed/18488142
xref: http://identifiers.org/pubmed/18515421
xref: http://identifiers.org/pubmed/15251227
xref: http://identifiers.org/pubmed/19935667
xref: http://identifiers.org/pubmed/13679574
comment: G protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it has become clear that this greatly oversimplifies the complexities of GPCR signaling (see Gurevich & Gurevich, 2008). The beta:gamma G-protein dimer is also involved in downstream signaling (Smrcka, 2008), and some receptors form part of metastable complexes of receptor and accessory proteins such as the arrestins. GPCRs are involved in many diverse signaling events (Kristiansen 2004), using a variety of pathways that include modulation of adenylyl cyclase, phospholipase C, the mitogen activated protein kinases (MAPKs), extracellular signal regulated kinase (ERK) c-Jun-NH2-terminal kinase (JNK) and p38 MAPK.

Evidence455
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16102047
xref: http://identifiers.org/pubmed/18814923
xref: http://identifiers.org/pubmed/7559569
xref: http://identifiers.org/pubmed/12588974
xref: http://identifiers.org/pubmed/19212140
comment: The G12/13 family is probably the least well characterized subtype, partly because G12/13 coupling is difficult to determine when compared with the other subtypes which predominantly rely on assay technologies that measure intracellular calcium. The G12/13 family are best known for their involvement in the processes of cell proliferation and morphology, such as stress fiber and focal adhesion formation. Interactions with Rho guanine nucleotide exchange factors (RhoGEFs) are thought to mediate many of these processes. (Buhl et al.1995, Sugimoto et al. 2003). Activation of Rho or the regulation of events through Rho is often taken as evidence of G12/13 signaling. Receptors that are coupled with G12/13 invariably couple with one or more other G protein subtypes, usually Gq.

UnificationXref880
type: UnificationXref
id: REACT_2551
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2551.2

Evidence454
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12101119
xref: http://identifiers.org/pubmed/9308960
xref: http://identifiers.org/pubmed/16212495
xref: http://identifiers.org/pubmed/8810315
xref: http://identifiers.org/pubmed/8276860
comment: Guanine nucleotide exchange factors (GEFs) activate GTPases by enhancing the exchange of bound GDP for GTP. Much evidence points to GEFs being critical mediators of Rho GTPase activation (Schmidt and Hall, 2002). Many GEFs are known to be highly specific for a particular GTPase, e.g. Fgd1/Cdc42 and p115RhoGEF/Rho (Hart et al., 1996, Zheng et al., 1996). Others have a broader spectrum and activate several GTPases, e.g. Vav1 for Rac, Rho, and Cdc42 (Hart et al, 1994).

UnificationXref881
type: UnificationXref
id: 113521
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113521

Evidence457
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18834311
comment: The classical role of the G-protein beta/gamma dimer was believed to be the inactivation of the alpha subunit, Gbeta/gamma was viewed as a negative regulator of Galpha signalling. It is now known that Gbeta/gamma subunits can directly modulate many effectors, including some also regulated by G alpha.

UnificationXref882
type: UnificationXref
id: REACT_3290
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3290.1

UnificationXref3721
type: UnificationXref
id: 77471
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=77471

Evidence456
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17916723
xref: http://identifiers.org/pubmed/17041586
comment: PI3K gamma (PI3KG) is a heterodimer consisting of a p110 catalytic subunit associated with a regulatory p101 or p84 subunit. PI3KG is most highly expressed in neutrophils, where the p101 form predominates (approximately 95%). G beta:gamma recruits PI3KG to the plasma membrane, both activating PI3KG and providing access to its substrate PIP2, which is converted to PIP3.

UnificationXref883
type: UnificationXref
id: CHEBI:61472
db: ChEBI

UnificationXref3720
type: UnificationXref
id: 5610445
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610445

UnificationXref3722
type: UnificationXref
id: REACT_5715
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5715.1

SequenceSite980
type: SequenceSite
position status: EQUAL
sequence position: 919

UnificationXref3723
type: UnificationXref
id: 5610446
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610446

SequenceSite981
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref3724
type: UnificationXref
id: 77461
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=77461

SequenceSite982
type: SequenceSite
position status: EQUAL
sequence position: 524

UnificationXref3725
type: UnificationXref
id: REACT_2916
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2916.1

PKC-theta (open): DAG (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry562
component stoichiometry: Stoichiometry561
component: SmallMolecule76
component: Protein700
xref: UnificationXref2160
cellular location: GO_0005886
comment: Reactome DB_ID: 5612926

UnificationXref3726
type: UnificationXref
id: 5610424
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610424

UnificationXref3727
type: UnificationXref
id: Q01560
db: UniProt

GLUT4 tetramer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry558
component: Protein699
xref: UnificationXref2142
cellular location: GO_0005886
comment: Reactome DB_ID: 5608295

UnificationXref3728
type: UnificationXref
id: 5610428
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610428

PDK1:PIP2,PIP3 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry559
component stoichiometry: Stoichiometry560
component: SmallMolecule74
component: Homologues of PDPK1
xref: UnificationXref2153
cellular location: GO_0005886
comment: Reactome DB_ID: 5612913

UnificationXref3729
type: UnificationXref
id: 5610447
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610447

p-3S,T844-RE1 dimer:ADP (yeast)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry553
component stoichiometry: Stoichiometry552
component: SmallMolecule73
component: p-3S,T844-IRE1 dimer (yeast)
xref: UnificationXref2079
xref: UnificationXref2080
cellular location: GO_0005789
comment: Reactome DB_ID: 535501

SequenceSite987
type: SequenceSite
position status: EQUAL
sequence position: 543

phospho p38:phospho MEF2 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry555
component stoichiometry: Stoichiometry556
component: Protein680
component: PhysicalEntity51
xref: UnificationXref2105
cellular location: GO_0005654
comment: Reactome DB_ID: 5614686

SequenceSite988
type: SequenceSite
position status: EQUAL
sequence position: 1

CPSF:capped intronless pre-mRNA:CBC complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry549
component stoichiometry: Stoichiometry550
component: CPSF (name copied from entity in Homo sapiens)
component: capped intronless pre-mRNA:CBC complex (name copied from entity in Homo sapiens)
xref: UnificationXref2061
cellular location: GO_0005654
comment: Reactome DB_ID: 5610690

SequenceSite989
type: SequenceSite
position status: EQUAL
sequence position: 524

p-3S,T844-IRE1 dimer (yeast)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry551
component: Protein679
xref: UnificationXref2076
xref: UnificationXref2075
cellular location: GO_0005789
comment: Reactome DB_ID: 535590

CPSF (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry542
component stoichiometry: Stoichiometry543
component stoichiometry: Stoichiometry544
component stoichiometry: Stoichiometry545
component: PhysicalEntity48
component: Protein674
component: Protein675
component: Protein676
xref: UnificationXref2053
cellular location: GO_0005654
comment: Reactome DB_ID: 5609172

SequenceSite983
type: SequenceSite
position status: EQUAL
sequence position: 123

capped intronless pre-mRNA:CBC complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry546
component stoichiometry: Stoichiometry547
component stoichiometry: Stoichiometry548
component: Protein678
component: PhysicalEntity49
component: Protein677
xref: UnificationXref2060
cellular location: GO_0005654
comment: Reactome DB_ID: 5610689

SequenceSite984
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite985
type: SequenceSite
position status: EQUAL
sequence position: 524

tRNA:mRNA:80S Ribosome Complex
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry538
component stoichiometry: Stoichiometry537
component stoichiometry: Stoichiometry539
component: SmallMolecule72
component: PhysicalEntity45
component: SmallMolecule71
xref: UnificationXref2037
xref: UnificationXref2038
cellular location: GO_0005829
comment: Reactome DB_ID: 141675

SequenceSite986
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref879
type: UnificationXref
id: 113533
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113533

Downstream signaling events of B Cell Receptor (BCR)
type: Pathway
data source: Provenance1
pathway component: Activation of NF-kappaB in B cells
pathway component: REACT 188931.3
evidence: Evidence285
xref: UnificationXref2286
xref: UnificationXref2285
pathway order: PathwayStep278
pathway order: PathwayStep271
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref877
type: UnificationXref
id: 113529
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113529

UnificationXref878
type: UnificationXref
id: REACT_5847
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5847.1

Evidence420
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9739761
xref: http://identifiers.org/pubmed/10508235
xref: http://identifiers.org/pubmed/15207811
comment: Platelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary endothelial cells and neurons.The PDGF family of growth factors is composed of four different polypeptide chains encoded by four different genes. The classical PDGF chains, PDGF-A and PDGF-B, and more recently discovered PDGF-C and PDGF-D. The four PDGF chains assemble into disulphide-bonded dimers via homo- or heterodimerization, and five different dimeric isoforms have been described so far; PDGF-AA, PDGF-AB, PDGF-BB, PDGF-CC and PDGF-DD. It is notable that no heterodimers involving PDGF-C and PDGF-D chains have been described. PDGF exerts its effects by binding to, and activating, two protein tyrosine kinase (PTK) receptors, alpha and beta. These receptors dimerize and undergo autophosphorylation. The phosphorylation sites then attract downstream effectors to transduct the signal into the cell.

UnificationXref875
type: UnificationXref
id: 2164814
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2164814

UnificationXref876
type: UnificationXref
id: REACT_160984
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160984.1

UnificationXref873
type: UnificationXref
id: REACT_5633
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5633.1

UnificationXref874
type: UnificationXref
id: CHEBI:1109
db: ChEBI

Evidence424
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17008595
xref: http://identifiers.org/pubmed/12062722
xref: http://identifiers.org/pubmed/9169492
comment: The free radical nitric oxide (NO), produced by endothelial NO synthase (eNOS), is an important vasoactive substance in normal vascular biology and pathophysiology. It plays an important role in vascular functions such as vascular dilation and angiogenesis (Murohara et al. 1998, Ziche at al. 1997). NO has been reported to be a downstream mediator in the angiogenic response mediated by VEGF, but the mechanism by which NO promotes neovessel formation is not clear (Babaei & Stewart 2002). Persistent vasodilation and increase in vascular permeability in the existing vasculature is observed during the early steps of angiogenesis, suggesting that these hemodynamic changes are indispensable during an angiogenic processes. NO production by VEGF can occur either through the activation of PI3K or through a PLC-gamma dependent manner. Once activated both pathways converge on AKT phosphorylation of eNOS, releasing NO (Lin & Sessa 2006). VEGF also regulates vascular permeability by promoting VE-cadherin endocytosis at the cell surface through a VEGFR-2SrcVav2RacPAK signalling axis.

UnificationXref871
type: UnificationXref
id: REACT_255300
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_255300.1

UnificationXref3754
type: UnificationXref
id: P40825
db: UniProt

Evidence423
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15467163
xref: http://identifiers.org/pubmed/8782602
xref: http://identifiers.org/pubmed/7526779
xref: http://identifiers.org/pubmed/9173876
comment: Nitric oxide (NO) is produced from L-arginine by the family of nitric oxide synthases (NOS) enzymes, forming the free radical NO and citrulline as byproduct. The cofactor tetrahydrobiopterin (BH4) is an essential requirement for the delivery of an electron to the intermediate in the catalytic cycle of NOS.

UnificationXref872
type: UnificationXref
id: 113600
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113600

UnificationXref3753
type: UnificationXref
id: REACT_17687
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_17687.1

Evidence422
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19583767
xref: http://identifiers.org/pubmed/15476407
comment: The cofactor tetrahydrobiopterin (BH4) ensures endothelial nitric oxide synthase (eNOS) couples electron transfer to L-arginine oxidation (Berka et al. 2004). During catalysis, electrons derived from NADPH transfer to the flavins FAD and FMN in the reductase domain of eNOS and then on to the ferric heme in the oxygenase domain of eNOS. BH4 can donate an electron to intermediates in this electron transfer and is oxidised in the process, forming the BH3 radical. This radical can be reduced back to BH4 by iron, completing the cycle and forming ferrous iron again. Heme reduction enables O2 binding and L-arginine oxidation to occur within the oxygenase domain (Stuehr et al. 2009).

UnificationXref3752
type: UnificationXref
id: 379700
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379700

Evidence421
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10376602
xref: http://identifiers.org/pubmed/10376603
xref: http://identifiers.org/pubmed/10469573
comment: HSP90 serves as a scaffold to promote productive interaction between AKT1 and eNOS. Due to the proximity of these proteins once complexed with HSP90, AKT1 phosphorylates eNOS at Ser1177. When Ser1177 is phosphorylated, the level of NO production is elevated two- to three-fold above basal level.

UnificationXref870
type: UnificationXref
id: 5618280
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618280

UnificationXref3751
type: UnificationXref
id: REACT_17504
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_17504.1

Evidence428
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16861033
comment: PKC contains a N-terminal C2 like domain, a pseudosubstrate (PS), DAG binding (C1) domain and a C-terminal kinase domain. The PS sequence resembles an ideal substrate with the exception that it contains an alanine residue instead of a substrate serine residue. It is bound to the kinase domain in the resting state. As a result, PKC is maintained in a closed inactive state, inaccessible to cellular substrates. On stimulation of receptors there is an increase in intracellular calcium and diacylglycerol (DAG) levels which leads to the activation of PKC and its translocation from the cytosol to the plasma membrane. PKCs tether to the plasma membrane through DAG binding to the C1 domain. This confers a high-affinity interaction between PKC and the membrane, leading to a massive conformational change that releases the PS domain from the catalytic site, the system becomes both competent and accessible (Colon-Gonzalez & Kazanietz 2006).

UnificationXref3750
type: UnificationXref
id: 379731
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379731

Evidence427
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9218480
xref: http://identifiers.org/pubmed/10421574
comment: After phosphorylation by PDK1, PKC undergoes autophosphorylation at two sites important for PKC activity, one in the turn motif (Thr-642 in PKCB) and the second in the hydrophobic phosphorylation motif (Ser-661 in PKCB). These phosphorylations render the enzyme catalytically competent but still inactive; diacylglycerol (DAG) and calcium are required for full activation.

Evidence426
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12840507
xref: http://identifiers.org/pubmed/9888881
xref: http://identifiers.org/pubmed/11805327
xref: http://identifiers.org/pubmed/10327068
xref: http://identifiers.org/pubmed/9889098
xref: http://identifiers.org/pubmed/8903320
comment: Protein kinase C (PKC) activation enhances angiogenesis by participating in the intracellular signaling of vascular endothelial growth factor (VEGF) in endothelial cells. VEGF can activate several PKC isoforms including alpha, beta, delta and zeta isoforms. Their activation is preceded by the activation of PLC gamma (Suzuma et al. 2002, Xia et al. 1996, Takahashi et al. 1999, Wellner et al. 1999). Before Protein kinase C (PKC) is competent to respond to second messengers it must first be phosphorylated at three conserved positions: the activation loop and two positions at the carboxyl terminus of the protein (Dutil et al. 1998). The phosphorylation of the activation loop appears to occur first and is mediated by phosphoinositide dependent protein kinases (PDKs). PDK1 phosphorylates PKCs at a critical Thr (T) residue in the activation loop, a requirement for PKC to gain catalytic competency (Toker 2003).

Evidence425
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/14724572
xref: http://identifiers.org/pubmed/16966330
comment: CDC42 is involved in the formation of filopodia with potential functions in guidance and migration in response to a VEGF gradient. CDC42 is activated downstream of VEGFR2 and involved in the formation of stress fibres by contributing to the activation of the p38 pathway. The activation of CDC42 may rely on FYN activity but the precise mechanism that leads to activation is not known (Lamalice et al. 2004, 2006).

CCNB1:p-T14,Y15,T161-CDK1 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry468
component stoichiometry: Stoichiometry469
component: Protein630
component: Protein509
xref: UnificationXref1779
cellular location: GO_0005654
comment: Reactome DB_ID: 5611781

UnificationXref1610
type: UnificationXref
id: REACT_247514
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_247514.1

p-4S-CCNB1:p-T161-CDK1 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry470
component stoichiometry: Stoichiometry471
component: Protein516
component: Protein631
xref: UnificationXref1787
cellular location: GO_0005654
comment: Reactome DB_ID: 5611790

UnificationXref1611
type: UnificationXref
id: 5618007
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618007

Evidence429
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/14532121
xref: http://identifiers.org/pubmed/12391145
comment: VEGF mediated activation of ERK1/2 depends on the activity of PKC. Sphingosine kinase 1 (SPHK1) has been identified as the connecting link between PKC and Ras activation. Activated SPHK1 does not activate Ras-GEF directly but rather modulates Ras-GAP activity to favour Ras activation. VEGF-mediated stimulation of SPHK1 results from the direct phosphorylation of SPHK1 by PKC (Shu et al. 2002). S225 in SPHK1 may be the target site of phosphorylation (Piston et al. 2003).

CCNB1:p-T14,T161-CDK1 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry472
component stoichiometry: Stoichiometry473
component: Protein509
component: Protein638
xref: UnificationXref1792
cellular location: GO_0005654
comment: Reactome DB_ID: 5611809

UnificationXref1612
type: UnificationXref
id: REACT_246435
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_246435.1

UnificationXref3759
type: UnificationXref
id: 379722
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379722

CAK (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry476
component stoichiometry: Stoichiometry474
component stoichiometry: Stoichiometry475
component: Protein641
component: Protein639
component: Protein640
xref: UnificationXref1799
cellular location: GO_0005654
comment: Reactome DB_ID: 5610133

UnificationXref1613
type: UnificationXref
id: 5618008
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618008

http://identifiers.org/pubmed/19783045
type: PublicationXref
id: 19783045
author: Kongsuphol, Patthara
author: Kunzelmann, Karl
author: Schreiber, Rainer
author: Warth, R
author: Tian, Yuemin
author: Ousingsawat, Jiraporn
author: Aldehni, Fadi
db: Pubmed
title: Bestrophin and TMEM16-Ca(2+) activated Cl(-) channels with different functions
source: Cell Calcium 46:233-41
year: 2009

active nuclear Cyclin B1:Cdc2 complexes
type: Complex
data source: Provenance1
member physical entity: p-4S-CCNB1:p-T161-CDK1 (name copied from entity in Homo sapiens)
member physical entity: Complex69
xref: UnificationXref1831
cellular location: GO_0005654
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5611833

UnificationXref1614
type: UnificationXref
id: REACT_242056
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_242056.1

UnificationXref3757
type: UnificationXref
id: REACT_212992
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_212992.2

Cyclin B2:phospho-Cdc2(Thr 14, Thr 161) (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry483
component stoichiometry: Stoichiometry484
component: Protein546
component: Protein650
xref: UnificationXref1837
cellular location: GO_0005829
comment: Reactome DB_ID: 5611843

UnificationXref1615
type: UnificationXref
id: 68452
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68452

UnificationXref3758
type: UnificationXref
id: CHEBI:29172
db: ChEBI

UnificationXref1616
type: UnificationXref
id: REACT_4386
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4386.1

UnificationXref3755
type: UnificationXref
id: 5613515
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613515

UnificationXref1617
type: UnificationXref
id: 69172
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=69172

UnificationXref3756
type: UnificationXref
id: 5613517
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613517

UnificationXref1618
type: UnificationXref
id: REACT_4394
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4394.1

UnificationXref1619
type: UnificationXref
id: P04819
db: UniProt

http://identifiers.org/pubmed/3893466
type: PublicationXref
id: 3893466
author: Jornvall, H
db: Pubmed
title: Alcohol dehydrogenases, aldehyde dehydrogenases, and related enzymes
source: Alcohol 2:61-6
year: 1985

Cyclin B1:phospho-Cdc2(Thr 161, Thr 14, Tyr 15) (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry462
component stoichiometry: Stoichiometry463
component: Protein621
component: Protein539
xref: UnificationXref1766
cellular location: GO_0005829
comment: Reactome DB_ID: 5611744

phospho-cyclin B1(CRS):phosph-Cdc2(Thr 161) (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry464
component stoichiometry: Stoichiometry465
component: Protein622
component: Protein440
xref: UnificationXref1774
cellular location: GO_0005829
comment: Reactome DB_ID: 5611776

nuclear Cyclin B1:Cdc2 complexes
type: Complex
data source: Provenance1
member physical entity: CCNB1:p-T14,Y15,T161-CDK1 (name copied from entity in Homo sapiens)
member physical entity: p-4S-CCNB1:p-T161-CDK1 (name copied from entity in Homo sapiens)
member physical entity: CCNB1:p-T14-CDK1 (name copied from entity in Homo sapiens)
xref: UnificationXref1788
cellular location: GO_0005654
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5611791

CCNB1:p-T14-CDK1 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry467
component stoichiometry: Stoichiometry466
component: Protein509
component: Protein629
xref: UnificationXref1777
cellular location: GO_0005654
comment: Reactome DB_ID: 5611779

UnificationXref866
type: UnificationXref
id: 5611348
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611348

UnificationXref867
type: UnificationXref
id: REACT_261277
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_261277.1

UnificationXref868
type: UnificationXref
id: 5618279
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618279

UnificationXref869
type: UnificationXref
id: REACT_252688
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_252688.1

UnificationXref862
type: UnificationXref
id: P04147
db: UniProt

UnificationXref863
type: UnificationXref
id: 5611345
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611345

http://identifiers.org/pubmed/7890667
type: PublicationXref
id: 7890667
author: Liu, SM
author: Cheng, HF
author: Wong, LP
author: King, K
author: Jiang, MJ
author: Chen, CL
author: Lomasney, JW
db: Pubmed
title: Cloning and identification of amino acid residues of human phospholipase C delta 1 essential for catalysis
source: J Biol Chem 270:5495-505
year: 1995

Evidence431
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16633338
xref: http://identifiers.org/pubmed/13678960
xref: http://identifiers.org/pubmed/16336962
xref: http://identifiers.org/pubmed/19230644
xref: http://identifiers.org/pubmed/17344076
xref: http://identifiers.org/pubmed/7596435
xref: http://identifiers.org/pubmed/23216836
comment: Angiogenesis is the formation of new blood vessels from preexisting vasculature. One of the most important proangiogenic factors is vascular endothelial growth factor (VEGF). VEGF exerts its biologic effect through interaction with transmembrane tyrosine kinase receptors VEGFR, selectively expressed on vascular endothelial cells. VEGFA signaling through VEGFR2 is the major pathway that activates angiogenesis by inducing the proliferation, survival, sprouting and migration of endothelial cells (ECs), and also by increasing endothelial permeability (Lohela et al. 2009, Shibuya & Claesson-Welsh 2006, Claesson-Welsh & Welsh, 2013). The critical role of VEGFR2 in vascular development is highlighted by the fact that VEGFR2-/- mice die at E8.5-9.5 due to defective development of blood islands, endothelial cells and haematopoietic cells (Shalaby et al. 1995).

UnificationXref864
type: UnificationXref
id: 5611346
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611346

Evidence430
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/14670956
xref: http://identifiers.org/pubmed/8321321
xref: http://identifiers.org/pubmed/12776187
comment: VEGFR2 stimulates ERK not via GRB2-SOS-RAS, but via pY1175-dependent phosphorylation of PLC gamma and subsequent activation of PKCs. PKC plays an important mediatory role in the proliferative Ras/Raf/MEK/ERK pathway. PKC alpha can intersect the Ras/Raf/MEK/ERK cascade at the level of Ras (Clark et al. 2004) or downstream of Ras through direct phosphorylation of Raf (Kolch et al. 1993). VEGF stimulation leads to Ras activation in a Ras-guanine nucleotide exchange factor (GEF) independent mechanism. It rather relies on modulating the regulation of Ras-GTPase activating protein (GAP) than regulation of Ras-GEFS (Wu et al. 2003).

UnificationXref865
type: UnificationXref
id: 5611347
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611347

Evidence433
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19540337
xref: http://identifiers.org/pubmed/2004790
xref: http://identifiers.org/pubmed/17350321
xref: http://identifiers.org/pubmed/16475976
xref: http://identifiers.org/pubmed/15526160
xref: http://identifiers.org/pubmed/7688988
xref: http://identifiers.org/pubmed/16483568
comment: Stem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival and differentiation of hematopoetic progenitors, melanocytes and germ cells.(Linnekin 1999, Ronnstrand 2004, Lennartsson and Ronnstrand 2006). The receptor for SCF is KIT, a tyrosine kinase receptor (RTK) closely related to the receptors for platelet derived growth factor receptor, colony stimulating factor 1 (Linnekin 1999) and Flt3 (Rosnet et al. 1991). Four isoforms of c-Kit have been identified in humans. Alternative splicing results in isoforms of KIT differing in the presence or absence of four residues (GNNK) in the extracellular region. This occurs due to the use of an alternate 5' splice donor site. These GNNK+ and GNNK- variants are co-expressed in most tissues; the GNNK- form predominates and was more strongly tyrosine-phosphorylated and more rapidly internalized (Ronnstrand 2004). There are also splice variants that arise from alternative usage of splice acceptor site resulting in the presence or absence of a serine residue (Crosier et al., 1993). Finally, there is an alternative shorter transcript of KIT expressed in postmeiotic germ cells in the testis which encodes a truncated KIT consisting only of the second part of the kinase domain and thus lackig the extracellular and transmembrane domains as well as the first part of the kinase domain (Rossi et al. 1991). Binding of SCF homodimers to KIT results in KIT homodimerization followed by activation of its intrinsic tyrosine kinase activity. KIT stimulation activates a wide array of signalling pathways including MAPK, PI3K and JAK/STAT (Reber et al. 2006, Ronnstrand 2004). Defects of KIT in humans are associated with different genetic diseases and also in several types of cancers like mast cell leukaemia, germ cell tumours, certain subtypes of malignant melanoma and gastrointestinal tumours.

UnificationXref3741
type: UnificationXref
id: 5610491
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610491

Evidence432
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15585754
xref: http://identifiers.org/pubmed/16633338
xref: http://identifiers.org/pubmed/16835467
xref: http://identifiers.org/pubmed/13678960
xref: http://identifiers.org/pubmed/16336962
comment: In normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angiogenesis). In tumor progression, activation of VEGF pathways promotes tumor vascularization, facilitating tumor growth and metastasis. Abnormal VEGF function is also associated with inflammatory diseases including atherosclerosis, and hyperthyroidism. The members of the VEGF and VEGF-receptor protein families have distinct but overlapping ligand-receptor specificities, cell-type expression, and function. VEGF-receptor activation in turn regulates a network of signaling processes in the body that promote endothelial cell growth, migration and survival (Hicklin and Ellis, 2005; Shibuya and Claesson-Welsh, 2006). Molecular features of the VGF signaling cascades are outlined in the figure below (from Olsson et al. 2006; Nature Publishing Group). Tyrosine residues in the intracellular domains of VEGF receptors 1, 2,and 3 are indicated by dark blue boxes; residues susceptible to phosphorylation are numbered. A circled R indicates that phosphorylation is regulated by cell state (VEGFR2), by ligand binding (VEGFR1), or by heterodimerization (VEGFR3). Specific phosphorylation sites (boxed numbers) bind signaling molecules (dark blue ovals), whose interaction with other cytosolic signaling molecules (light blue ovals) leads to specific cellular (pale blue boxes) and tissue-level (pink boxes) responses in vivo. Signaling cascades whose molecular details are unclear are indicated by dashed arrows. DAG, diacylglycerol; EC, endothelial cell; eNOS, endothelial nitric oxide synthase; FAK, focal adhesion kinase; HPC, hematopoietic progenitor cell; HSP27, heat-shock protein-27; MAPK, mitogen-activated protein kinase; MEK, MAPK and ERK kinase; PI3K, phosphatidylinositol 3' kinase; PKC, protein kinase C; PLCgamma, phospholipase C-gamma; Shb, SH2 and beta-cells; TSAd, T-cell-specific adaptor. I…

UnificationXref3740
type: UnificationXref
id: 5610490
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5610490

Evidence435
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: ERBB2:EGFR and ERBB2:ERBB4 can directly recruit GRB2:SOS1 complex through phosphorylated C-tail tyrosines of EGFR (Y1068 and Y1086) and ERBB2 (Y1139) that serve as docking sites for GRB2 (Xie et al. 1995, Sepp-Lorenzino et al. 1996), which, again, results in SOS1-mediated guanyl-nucleotide exchange on RAS and activation of RAF and MAP kinases (Janes et al. 1994, Sepp-Lorenzino et al. 1996).

UnificationXref860
type: UnificationXref
id: 5609418
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609418

UnificationXref3743
type: UnificationXref
id: 5618103
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618103

Evidence434
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: All ERBB2 heterodimers, ERBB2:EGFR, ERBB2:ERBB3 and ERBB2:ERBB4, are able to activate RAF/MAP kinase cascade by recruiting SHC1 (Pinkas-Kramarski et al. 1996, Sepp-Lorenzino et al. 1996) to phosphorylated C-tail tyrosine residues in either EGFR (Y1148 and Y1173), ERBB2 (Y1196, Y1221, Y1222 and Y1248), ERBB3 (Y1328) or ERBB4 (Y1188 and Y1242 in JM-A CYT1 isoform, Y1178 and Y1232 in JM-B CYT1 isoform, Y1172 and Y1226 in JM-A CYT2 isoform). SHC1 recruitment is followed by phosphorylation (Segatto et al. 1993, Soler et al. 1994), and the phosphorylated SHC1 recruits GRB2:SOS1 complex (Xie et al. 1995), which leads to SOS1-mediated guanyl-nucleotide exchange on RAS (Xie et al. 1995) and downstream activation of RAF and MAP kinases.

UnificationXref861
type: UnificationXref
id: 5609459
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609459

UnificationXref3742
type: UnificationXref
id: REACT_259538
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_259538.1

Evidence437
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Activation of PLCG1 signaling is observed only in the presence of ERBB2:EGFR heterodimers, with PLCG1 binding to phosphorylated tyrosine Y992 and Y1173 in the C-tail of EGFR (Chattopadhyay et al. 1999), and potentially Y1023 in the C-tail of ERBB2 (Fazioli et al. 1991, Cohen et al. 1996).

Evidence436
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: ERBB2:ERBB3 and ERBB2:ERBB4cyt1 heterodimers activate PI3K signaling by direct binding of PI3K regulatory subunit p85 (Yang et al. 2007, Cohen et al. 1996, Kaushansky et al. 2008) to phosphorylated tyrosine residues in the C-tail of ERBB3 (Y1054, Y1197, Y1222, Y1224, Y1276 and Y1289) and ERBB4 CYT1 isoforms (Y1056 in JM-A CYT1 isoform and Y1046 in JM-B CYT1 isoform). Regulatory subunit p85 subsequently recruits catalytic subunit p110 of PI3K, resulting in the formation of active PI3K, conversion of PIP2 to PIP3, and PIP3-mediated activation of AKT signaling (Junttila et al. 2009, Kainulainen et al. 2000). Heterodimers of ERBB2 and EGFR recruit PI3K indirectly, through GRB2:GAB1 complex (Jackson et al. 2004), which again leads to PIP3-mediated activation of AKT signaling.

Evidence439
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: All splicing isoforms of ERBB4 possess two tyrosine residues in the C-tail that serve as docking sites for SHC1 (Kaushansky et al. 2008, Pinkas-Kramarski et al. 1996, Cohen et al. 1996). Once bound to ERBB4, SHC1 becomes phosphorylated on tyrosine residues by the tyrosine kinase activity of ERBB4, which enables it to recruit the complex of GRB2 and SOS1, resulting in the guanyl-nucleotide exchange on RAS and activation of RAF and MAP kinase cascade (Kainulainen et al. 2000).

Evidence438
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: ERBB2, also known as HER2 or NEU, is a receptor tyrosine kinase (RTK) belonging to the EGFR family. ERBB2 possesses an extracellular domain that does not bind any known ligand, contrary to other EGFR family members, a single transmembrane domain, and an intracellular domain consisting of an active kinase and a C-tail with multiple tyrosine phosphorylation sites. Inactive ERBB2 is associated with a chaperone heat shock protein 90 (HSP90) and its co-chaperone CDC37 (Xu et al. 2001, Citri et al. 2004, Xu et al. 2005). In addition, ERBB2 is associated with ERBB2IP (also known as ERBIN or LAP2), a protein responsible for proper localization of ERBB2. In epithelial cells, ERBB2IP restricts expression of ERBB2 to basolateral plasma membrane regions (Borg et al. 2000). ERBB2 becomes activated by forming a heterodimer with another ligand-activated EGFR family member, either EGFR, ERBB3 or ERBB4, which is accompanied by dissociation of chaperoning proteins HSP90 and CDC37 (Citri et al. 2004), as well as ERBB2IP (Borg et al. 2000) from ERBB2. ERBB2 heterodimers function to promote cell proliferation, cell survival and differentiation, depending on the cellular context. ERBB2 can also be activated by homodimerization when it is overexpressed, in cancer for example. In cells expressing both ERBB2 and EGFR, EGF stimulation of EGFR leads to formation of both ERBB2:EGFR heterodimers (Wada et al. 1990, Karunagaran et al. 1996) and EGFR homodimers. Heterodimers of ERBB2 and EGFR trans-autophosphorylate on twelve tyrosine residues, six in the C-tail of EGFR and six in the C-tail of ERBB2 - Y1023, Y1139, Y1196, Y1221, Y1222 and Y1248 (Margolis et al. 1989, Hazan et al. 1990,Walton et al. 1990, Helin et al. 1991, Ricci et al. 1995, Pinkas-Kramarski 1996). Phosphorylated tyrosine residues in the C-tail of EGFR and ERBB2 serve as docking sites for downstream signaling molecules. Three key signaling pathways activated by ERBB2:EGFR heterodimers are RAF/MAP kinase cascade, PI3K-induced AKT …

DNA polymerase alpha:primase:DNA polymerase alpha:G-strand extended telomere end (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry505
component stoichiometry: Stoichiometry503
component: DNA polymerase epsilon:G-strand extended telomere end (name copied from entity in Homo sapiens)
component: Complex85
xref: UnificationXref1932
cellular location: GO_0005654
comment: Reactome DB_ID: 5611934

UnificationXref1601
type: UnificationXref
id: REACT_246292
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_246292.1

UnificationXref3748
type: UnificationXref
id: REACT_261636
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_261636.1

DNA polymerase epsilon:G-strand extended telomere end (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry504
component: Complex84
xref: UnificationXref1931
cellular location: GO_0005654
comment: Reactome DB_ID: 5611933

UnificationXref1602
type: UnificationXref
id: P15873
db: UniProt

UnificationXref3749
type: UnificationXref
id: CHEBI:17732
db: ChEBI

Telomerase RNP:Telomeric Chromosome End with an Additional single Stranded Telomere repeat (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry499
component stoichiometry: Stoichiometry500
component: SmallMolecule62
component: Telomerase RNP (name copied from entity in Homo sapiens)
xref: UnificationXref1917
cellular location: GO_0005654
comment: Reactome DB_ID: 5611467

Telomerase Holoenzyme:Telomeric RNP End with Two Additional Single Stranded Telomere Repeats (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry502
component stoichiometry: Stoichiometry501
component: SmallMolecule63
component: Telomerase RNP (name copied from entity in Homo sapiens)
xref: UnificationXref1924
cellular location: GO_0005654
comment: Reactome DB_ID: 5611472

UnificationXref1600
type: UnificationXref
id: 5608170
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608170

UnificationXref1605
type: UnificationXref
id: 5608176
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608176

UnificationXref3744
type: UnificationXref
id: REACT_191540
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_191540.3

UnificationXref1606
type: UnificationXref
id: 5608177
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608177

UnificationXref3745
type: UnificationXref
id: 5618104
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618104

RNA primer:G-strand extended telomere end:DNA polymerase alpha:primase complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry506
component stoichiometry: Stoichiometry507
component stoichiometry: Stoichiometry508
component: Complex85
component: PhysicalEntity29
component: SmallMolecule63
xref: UnificationXref1933
cellular location: GO_0005654
comment: Reactome DB_ID: 5611935

UnificationXref1603
type: UnificationXref
id: 5608174
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608174

UnificationXref3746
type: UnificationXref
id: REACT_191539
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_191539.3

http://identifiers.org/pubmed/8662720
type: PublicationXref
id: 8662720
author: Korenberg, J
author: Garrow, TA
author: Qi, H
author: Choi, YJ
author: Shane, B
author: Chen, L
db: Pubmed
title: Purification and properties of human cytosolic folylpoly-gamma-glutamate synthetase and organization, localization, and differential splicing of its gene
source: J Biol Chem 271:13077-87
year: 1996

UnificationXref1604
type: UnificationXref
id: 5608175
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608175

UnificationXref3747
type: UnificationXref
id: 5618069
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618069

UnificationXref1609
type: UnificationXref
id: 5608179
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608179

SCF-beta-TrCP:phospho-Emi1 complexes (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry488
component stoichiometry: Stoichiometry489
component: PhysicalEntity7
component: SCF-beta-TrCP1 complex (name copied from entity in Homo sapiens)
xref: UnificationXref1868
cellular location: GO_0005829
comment: Reactome DB_ID: 5611886

http://identifiers.org/pubmed/7890675
type: PublicationXref
id: 7890675
author: Haucke, V
author: Schatz, G
author: Hahne, K
author: Lithgow, T
author: Rospert, S
db: Pubmed
title: The yeast mitochondrial protein import receptor Mas20p binds precursor proteins through electrostatic interaction with the positively charged presequence
source: J Biol Chem 270:5565-70
year: 1995

UnificationXref1607
type: UnificationXref
id: REACT_262464
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_262464.1

UnificationXref1608
type: UnificationXref
id: 5608178
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608178

Telomerase RNP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry496
component stoichiometry: Stoichiometry494
component stoichiometry: Stoichiometry495
component: Protein667
component: PhysicalEntity28
component: Protein666
xref: UnificationXref1909
cellular location: GO_0005654
comment: Reactome DB_ID: 5611465

Telomerase RNP Bound and base-paired to the Telomeric Chromosome End (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry498
component stoichiometry: Stoichiometry497
component: SmallMolecule61
component: Telomerase RNP (name copied from entity in Homo sapiens)
xref: UnificationXref1910
cellular location: GO_0005654
comment: Reactome DB_ID: 5611466

SCF-beta-TrCP1 complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry485
component stoichiometry: Stoichiometry486
component stoichiometry: Stoichiometry487
component: Protein656
component: Protein657
component: Protein658
xref: UnificationXref1867
cellular location: GO_0005829
comment: Reactome DB_ID: 5611885

SCF-associated multiubiquitinated Emi1complexes (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry492
component stoichiometry: Stoichiometry491
component: PhysicalEntity6
component: SCF-beta-TrCP:phospho-Emi1 complexes (name copied from entity in Homo sapiens)
xref: UnificationXref1869
cellular location: GO_0005829
comment: Reactome DB_ID: 5611887

Evidence405
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10712923
comment: RIT and RIN are two small guanine nucleotide binding proteins that share more than 50% sequence identity with RAS, including highly conserved core effector domains. Unlike RAS, the C termini of RIT and RIN lack a typical prenylation motif (CAAX, XXCC, or CXC) required for the association of RAS proteins with the plasma membrane. RIT is expressed in all tissues, whereas RIN is neuron-specific. They have similar signalling properties and are activated by NGF through unknown exchange factors. They signal to ERKs and p38 MAP kinase. They mainly lead to p38 activation via the BRAF-MEK kinase cascade.

UnificationXref3771
type: UnificationXref
id: CHEBI:29152
db: ChEBI

Evidence406
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9069267
comment: The adaptor protein Frs2 (Fibroblast growth factor receptor substrate 2) can mediate the prolonged activation of the MAPK (ERK) cascade.

UnificationXref3772
type: UnificationXref
id: 379719
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379719

Evidence403
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16699811
xref: http://identifiers.org/pubmed/16939974
xref: http://identifiers.org/pubmed/16025106
xref: http://identifiers.org/pubmed/12671646
comment: Besides signalling through the tyrosine kinase receptors TRK A, B, and C, the mature neurotrophins NGF, BDNF, and NT3/4 signal through their common receptor p75NTR. NGF binding to p75NTR activates a number of downstream signalling events controlling survival, death, proliferation, and axonogenesis, according to the cellular context. p75NTR is devoid of enzymatic activity, and signals by recruiting other proteins to its own intracellular domain. p75 interacting proteins include NRIF, TRAF2, 4, and 6, NRAGE, necdin, SC1, NADE, RhoA, Rac, ARMS, RIP2, FAP and PLAIDD. Here we annotate only the proteins for which a clear involvement in p75NTR signalling was demonstrated. A peculiarity of p75NTR is the ability to bind the pro-neurotrophins proNGF and proBDNF. Proneurotrophins do not associate with TRK receptors, whereas they efficiently signal cell death by apoptosis through p75NTR. The biological action of neurotrophins is thus regulated by proteolytic cleavage, with proforms preferentially activating p75NTR, mediating apoptosis, and mature forms activating TRK receptors, to promote survival. Moreover, the two receptors are utilised to differentially modulate neuronal plasticity. For instance, proBDNF-p75NTR signalling facilitates LTD, long term depression, in the hippocampus (Woo NH, et al, 2005), while BDNF-TRKB signalling promotes LTP (long term potentiation). Many biological observations indicate a functional interaction between p75NTR and TRKA signaling pathways.

UnificationXref1630
type: UnificationXref
id: REACT_260043
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_260043.1

Evidence404
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11520933
comment: Signalling through Shc adaptor proteins appears to be identical for both NGF and EGF. It leads to a fast, but transient, MAPK/ERK activation, which is insufficient to explain the prolonged activation of MAPK found in NGF-treated cells.

UnificationXref1631
type: UnificationXref
id: 5617995
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617995

UnificationXref3770
type: UnificationXref
id: REACT_15645
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15645.1

Evidence401
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Sphingomyielinase promotes the conversion of sphingomyelin to ceramide. Ceramide can activate JNK and other targets. The molecular details of the p75NTR-activated ceramide signalling cascade are only partially understood.

UnificationXref3775
type: UnificationXref
id: 5613521
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613521

Evidence402
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: PublicationXref960
comment: In certain cell types, ligand binding to p75NTR leads to ceramide production, which can mediate either cell survival (e.g. in noecotical subplate neurons) or apoptosis (e.g. in oligodendrocytes). Low levels of ceramide are also able to stimulate axonal outgrowth in hippocampal neurons.

UnificationXref3776
type: UnificationXref
id: 5613522
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613522

UnificationXref3773
type: UnificationXref
id: REACT_15780
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15780.1

Evidence400
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12787561
comment: p75NTR is a key regulator of neuronal apoptosis, both during development and after injury. Apoptosis is triggered by binding of either mature neurotrophin or proneurotrophin (proNGF, proBDNF). ProNGF is at least 10 times more potent than mature NGF in inducing apoptosis. TRKA signalling protects neurons from apoptosis. The molecular mechanisms involved in p75NTR-apoptosis are not well understood. The death signalling requires activation of c-JUN N-terminal Kinase (JNK), as well as transcriptional events. JNK activation appears to involve the receptor interacting proteins TRAF6, NRAGE, and Rac. The transcription events are thought to be regulated by another p75-interacting protein, NRIF. Two other p75-interacting proteins, NADE and Necdin, have been implicated in apoptosis, but their role is less clear.

UnificationXref3774
type: UnificationXref
id: P53852
db: UniProt

PAK1 dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry621
component: Protein716
xref: UnificationXref2535
cellular location: GO_0005829
comment: Reactome DB_ID: 5616749

RAC1/CDC42:PAK dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry623
component stoichiometry: Stoichiometry622
component: CDC42:GTP (name copied from entity in Homo sapiens)
component: PAK1 dimer (name copied from entity in Homo sapiens)
xref: UnificationXref2536
cellular location: GO_0005829
comment: Reactome DB_ID: 5616750

Mde1p:Zn++
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry643
component stoichiometry: Stoichiometry642
component: Protein815
component: SmallMolecule109
xref: UnificationXref2658
xref: UnificationXref2657
cellular location: GO_0005829
comment: Reactome DB_ID: 1237184

p-5Y-PKC-theta:DAG (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry641
component stoichiometry: Stoichiometry640
component: Protein814
component: SmallMolecule76
xref: UnificationXref2626
cellular location: GO_0005886
comment: Reactome DB_ID: 5617210

http://identifiers.org/pubmed/15585605
type: PublicationXref
id: 15585605
author: Takeda, K
author: Akira, S
db: Pubmed
title: TIRAP/Mal, TRIF and TRAM. Differential utilization of these TIR
source: Int Immunol 17:1-14
year: 2005

p-MEK:ERK
type: Complex
data source: Provenance1
member physical entity: Complex46
member physical entity: Complex42
xref: UnificationXref2696
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5615825

SUP4 tRNA Promoter Complex
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry647
component stoichiometry: Stoichiometry646
component stoichiometry: Stoichiometry645
component stoichiometry: Stoichiometry644
component: PhysicalEntity12
component: Complex33
component: Complex32
component: Protein388
xref: UnificationXref2670
xref: UnificationXref2669
cellular location: GO_0005654
comment: Reactome DB_ID: 156599

PKA tetramer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry631
component stoichiometry: Stoichiometry630
component: Protein804
component: Protein800
xref: UnificationXref2589
cellular location: GO_0005829
comment: Reactome DB_ID: 5611154

RAC1/CDC42:p-S144,T423-PAK (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry627
component stoichiometry: Stoichiometry626
component: CDC42:GTP (name copied from entity in Homo sapiens)
component: Protein788
xref: UnificationXref2543
cellular location: GO_0005829
comment: Reactome DB_ID: 5616761

active PKC (alpha, gamma, delta) (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry636
component stoichiometry: Stoichiometry637
component: Protein813
component: SmallMolecule9
xref: UnificationXref2610
cellular location: GO_0005829
comment: Reactome DB_ID: 5611170

cAMP:PKA regulatory subunit (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry635
component stoichiometry: Stoichiometry634
component: Protein804
component: SmallMolecule106
xref: UnificationXref2593
cellular location: GO_0005829
comment: Reactome DB_ID: 5611155

UnificationXref1637
type: UnificationXref
id: 5617993
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617993

UnificationXref1636
type: UnificationXref
id: REACT_237693
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_237693.1

UnificationXref3779
type: UnificationXref
id: CHEBI:29176
db: ChEBI

UnificationXref1639
type: UnificationXref
id: P23748
db: UniProt

UnificationXref3778
type: UnificationXref
id: REACT_214281
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_214281.2

UnificationXref1638
type: UnificationXref
id: REACT_243956
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_243956.1

UnificationXref3777
type: UnificationXref
id: 5613524
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613524

UnificationXref1633
type: UnificationXref
id: 5618005
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618005

Evidence409
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10508738
comment: Neurotrophins utilize multiple pathways to activate ERKs (ERK1 and ERK2), a subgroup of the large MAP kinase (MAPK) family, from the plasma membrane. The major signalling pathways to ERKs are via RAS, ocurring from caveolae in the plasma membrane or from clathrin-coated vesicles, and via RAP1, taking place in early endosomes. Whereas RAS activation by NGF is transient, RAP1 activation by NGF is sustained for hours.

UnificationXref1632
type: UnificationXref
id: REACT_237144
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_237144.1

Evidence408
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9069267
xref: http://identifiers.org/pubmed/12765839
comment: After NGF binding, activated Trk receptors provide multiple docking sites for adaptor proteins and enzymes. Two docking proteins, the Ankyrin-Rich Membrane Spanning protein (ARMS/Kidins220) and Fibroblast growth factor receptor substrate 2 (Frs2), target signaling molecules in response to NGF stimulation and link receptor activation with the MAP kinase (also called the Extracellular signal-Regulated Kinase cascade, ERK) cascade, an essential process for growth factor-induced cell proliferation and differentiation. A feature of NGF signaling is the sustained activation of the MAPK cascade. This is achieved by the small G protein, Rap1 which binds to and activates B-Raf, an activator of the MAPK cascade. Rap1 is a member of the Ras family of G proteins and like all G proteins, Rap1 is in an inactive state when bound to GDP and is active when bound to GTP. A specific GEF (guanine nucleotide exchange factor) called C3G can activate Rap1 by exchanging GDP for GTP.

UnificationXref1635
type: UnificationXref
id: 5617996
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617996

Evidence407
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9069267
comment: ARMS (Ankyrin-Rich Membrane Spanning/Kidins 220) is a 220kD tetraspanning adaptor protein which becomes rapidly tyrosine phosphorylated by active Trk receptors. ARMS is another adaptor protein which is involved in the activation of Rap1 and the subsequent prolonged activation of the MAPK cascade.

UnificationXref1634
type: UnificationXref
id: REACT_245084
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_245084.1

Evidence414
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: On phosphorylation, ERK5 translocates to the nucleus.

Evidence415
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: The location of neurotrophin stimulation appears to determine the nature of the transcriptional response through differential uses of individual MAP kinases. The ERK5 pathway has a unique function in retrograde signalling; in contrast, ERK1/2, which mediate nuclear responses following direct cell body stimulation, does not transmit a retrograde signal. Following neurotrophin stimulation of distal axons, phosphorylated TRK receptors are endocytosed and transported to the cell bodies, where MEK5 phosphorylates ERK5, leading to ERK5 nuclear translocation, phosphorylation of transcription factors, and neuronal survival. In contrast, neurotrophin stimulation of the cell bodies causes concurrent activation and nuclear transport of ERK1/2 as well as ERK5. Several distinctive features of the ERK5 pathway might be important for retrograde signalling. The ERK5 cascade does not depend on activation of the G-protein RAS. Instead, this pathway may use other G-proteins such as RAP that are associated with vesicles, or may not require any G-protein intermediate. Another distinctive feature is that the MEK5 isoform, which is expressed in the nervous system, exhibits a punctate staining pattern, suggesting a vesicular localization. ERK5 itself significantly differs from ERK1/2, and its substrate specificity also differs from ERK1/2. For instance, ERK5 directly activates transcription factors, including MEF2, that are not phosphorylated by ERK1/2. Conversely, ERK1/2, but not ERK5, activate transcription factors such as ELK1 and MITF.

UnificationXref1620
type: UnificationXref
id: 5608183
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608183

Evidence416
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8833451
comment: An important function of the kinase cascade triggered by neurotrophins is to induce the phosphorylation and activation of transcription factors in the nucleus to initiate new programs of gene expression. Transcription factors directly activated by neurotrophin signalling are responsible for induction of immediate-early genes, many of which are transcription factors. These in turn are involved in the induction of delayed-early genes.

UnificationXref3760
type: UnificationXref
id: REACT_15652
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15652.1

Evidence417
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10579918
xref: http://identifiers.org/pubmed/11520933
xref: http://identifiers.org/pubmed/10851172
xref: http://identifiers.org/pubmed/12676795
comment: Trk receptors signal from the plasma membrane and from intracellular membranes, particularly from early endosomes. Signalling from the plasma membrane is fast but transient; signalling from endosomes is slower but long lasting. Signalling from the plasma membrane is annotated here. TRK signalling leads to proliferation in some cell types and neuronal differentiation in others. Proliferation is the likely outcome of short term signalling, as observed following stimulation of EGFR (EGF receptor). Long term signalling via TRK receptors, instead, was clearly shown to be required for neuronal differentiation in response to neurotrophins.

UnificationXref3761
type: UnificationXref
id: CHEBI:29265
db: ChEBI

Evidence410
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10579907
xref: http://identifiers.org/pubmed/12676795
comment: The activation of phosphlipase C-gamma (PLC-gamma) and subsequent mobilization of calcium from intracellular stores are essential for neurotrophin secretion. PLC-gamma is activated through the phosphorylation by TrkA receptor kinase and this form hydrolyses PIP2 to generate inositol tris-phosphate (IP3) and diacylglycerol (DAG). IP3 promotes the release of Ca2+ from internal stores and this results in activation of enzymes such as protein kinase C and Ca2+ calmodulin-regulated protein kinases.

UnificationXref3762
type: UnificationXref
id: 379728
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379728

Evidence411
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Several guanine exchange factors (GEFs) for the Rho family of GTPases contain PH domains that bind to PIP3. RhoA protein activation is a mechanism whereby PI3K acts independently of AKT.

UnificationXref3763
type: UnificationXref
id: REACT_15840
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15840.1

Evidence412
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10579926
xref: http://identifiers.org/pubmed/12123609
comment: PI3K/AKT signalling is a major regulator of neuron survival. It blocks cell death by both impinging on the cytoplasmic cell death machinery and by regulating the expression of genes involved in cell death and survival. In addition, it may also use metabolic pathways to regulate cell survival.The PI3K/AKT pathway also affects axon diameter and branching (Marcus et al, 2002) and regulates small G proteins like RhoA (Vanhaesebroeck, B and Waterman, MD, 1999), which control the behaviour of the F-actin cytoskeleton. Moreover, through its connection with the TOR pathway, it promotes translation of a subset of mRNAs.

UnificationXref3764
type: UnificationXref
id: P38707
db: UniProt

Evidence413
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase family. ERK5 is twice the size of the ERK1/2, containing a conserved amino terminal kinase domain that is 53% identical to ERK1/2, and a unique carboxyterminal region which contains potential binding sites for signalling molecules such as CRK, PI3 kinase and SRC. The second proline-rich region may interact with actin, targeting the kinase to a specific location in the cell. In contrast to ERK1 and ERK2, which are activated by neurotrophins (NTs), cAMP, and neuronal activity in neurons, ERK5 appears to be activated only by neurotrophins. The small GTPase Rap1 and the MEKK2 or MEKK3 kinases are critical upstream signaling molecules mediating neurotrophin stimulation of ERK5 in neurons. MEKK2 or MEKK3 activate MEK5, which appears to be localised in intracellular vesicles. MEK5 then activates ERK5. Once phosphorylated, ERK5 translocates to the nucleus.

UnificationXref3765
type: UnificationXref
id: 5613549
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613549

p-ERK dimer
type: Complex
data source: Provenance1
member physical entity: Complex44
member physical entity: Complex48
xref: UnificationXref2705
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5615828

Activated mTORC1 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry658
component stoichiometry: Stoichiometry653
component stoichiometry: Stoichiometry654
component stoichiometry: Stoichiometry657
component: Protein710
component: Rheb:GTP (name copied from entity in Homo sapiens)
component: Protein820
component: Protein707
xref: UnificationXref2719
cellular location: GO_0005829
comment: Reactome DB_ID: 5611601

p-MEK:p-ERK
type: Complex
data source: Provenance1
member physical entity: Complex47
member physical entity: Complex43
xref: UnificationXref2697
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5615819

UniProt:Q05027
type: ProteinReference
name: TAF9
xref: UnificationXref3373
organism: http://identifiers.org/taxonomy/4932

V-ATPase:ATP6AP1 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry698
component stoichiometry: Stoichiometry685
component stoichiometry: Stoichiometry686
component: ATP6V1 (name copied from entity in Homo sapiens)
component: ATP6V0 (name copied from entity in Homo sapiens)
component: PhysicalEntity69
xref: UnificationXref2858
cellular location: endosome membrane
comment: Reactome DB_ID: 5610367

PIP3:AKT2 complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry676
component stoichiometry: Stoichiometry677
component: Protein842
component: SmallMolecule111
xref: UnificationXref2786
cellular location: GO_0005886
comment: Reactome DB_ID: 5610819

PIP3:PDK1 complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry674
component stoichiometry: Stoichiometry673
component: SmallMolecule111
component: Homologues of PDPK1
xref: UnificationXref2779
cellular location: GO_0005886
comment: Reactome DB_ID: 5610804

p-AMPK heterotrimer:AMP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry669
component stoichiometry: Stoichiometry670
component: p-AMPK heterotrimer (name copied from entity in Homo sapiens)
component: SmallMolecule70
xref: UnificationXref2763
cellular location: GO_0005829
comment: Reactome DB_ID: 5613689

AMPK heterotrimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry668
component stoichiometry: Stoichiometry667
component stoichiometry: Stoichiometry666
component: Protein835
component: Protein838
component: Protein831
xref: UnificationXref2758
cellular location: GO_0005829
comment: Reactome DB_ID: 5612736

p-AMPK heterotrimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry664
component stoichiometry: Stoichiometry663
component stoichiometry: Stoichiometry665
component: Protein835
component: Protein828
component: Protein831
xref: UnificationXref2754
cellular location: GO_0005829
comment: Reactome DB_ID: 5612741

http://identifiers.org/pubmed/15031527
type: PublicationXref
id: 15031527
author: Matsumoto, M
author: Seya, T
author: Funami, K
author: Oshiumi, H
db: Pubmed
title: Toll-like receptor 3: a link between toll-like receptor, interferon and viruses
source: Microbiol Immunol 48:147-54
year: 2004

Rheb:GTP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry655
component stoichiometry: Stoichiometry656
component: PhysicalEntity7
component: SmallMolecule26
xref: UnificationXref2716
cellular location: GO_0005829
comment: Reactome DB_ID: 5611596

UnificationXref1629
type: UnificationXref
id: 5617998
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617998

UnificationXref1628
type: UnificationXref
id: REACT_239906
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_239906.1

UnificationXref3767
type: UnificationXref
id: REACT_222434
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_222434.2

UnificationXref1627
type: UnificationXref
id: 5618009
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618009

UnificationXref3766
type: UnificationXref
id: 5613551
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613551

UnificationXref1626
type: UnificationXref
id: REACT_243277
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_243277.1

UnificationXref3769
type: UnificationXref
id: 379725
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379725

UnificationXref1625
type: UnificationXref
id: 5618010
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618010

UnificationXref3768
type: UnificationXref
id: CHEBI:29167
db: ChEBI

Evidence419
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9739761
xref: http://identifiers.org/pubmed/10508235
xref: http://identifiers.org/pubmed/1374684
comment: The role of autophosphorylation sites on PDGF receptors are to provide docking sites for downstream signal transduction molecules which contain SH2 domains. The SH2 domain is a conserved motif of around 100 amino acids that can bind a phosphorylated tyrosine residue. These downstream molecules are activated upon binding to, or phosphorylated by, the receptor kinases intrinsic to PDGF receptors. Some of the dowstream molecules are themselves enzymes, such as phosphatidylinositol 3'-kinase (PI3K), phospholipase C (PLC-gamma), the Src family of tyrosine kinases, the tyrosine phosphatase SHP2, and a GTPase activating protein (GAP) for Ras. Others such as Grb2 are adaptor molecules which link the receptor with downstream catalytic molecules.

UnificationXref1624
type: UnificationXref
id: REACT_238470
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_238470.1

UniProt:P18961
type: ProteinReference
name: YPK2
xref: UnificationXref77
organism: http://identifiers.org/taxonomy/4932

Evidence418
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Neurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in minute amounts, by a variety of tissues. They signal through two types of receptors: TRK tyrosine kinase receptors (TRKA, TRKB, TRKC), which specifically interact with the different neurotrophins, and p75NTR, which interacts with all neurotrophins. TRK receptors are reported in a variety of tissues in addition to neurons. p75NTRs are also widespread. Neurotrophins and their receptors are synthesized as several different splice variants, which differ in terms of their biological activities. The nerve growth factor (NGF) was the first growth factor to be identified and has served as a model for studying the mechanisms of action of neurotrophins and growth factors. The mechanisms by which NGF generates diverse cellular responses have been studied extensively in the rat pheochromocytoma cell line PC12. When exposed to NGF, PC12 cells exit the cell cycle and differentiate into sympathetic neuron-like cells. Current data show that signalling by the other neurotrophins is similar to NGF signalling.

UnificationXref1623
type: UnificationXref
id: 5618011
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618011

http://identifiers.org/pubmed/19489725
type: PublicationXref
id: 19489725
author: Joazeiro, Claudio A
author: Deshaies, RJ
db: Pubmed
title: RING domain E3 ubiquitin ligases
source: Annu Rev Biochem 78:399-434
year: 2009

UnificationXref1622
type: UnificationXref
id: REACT_236238
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_236238.1

UnificationXref1621
type: UnificationXref
id: 5608185
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608185

http://identifiers.org/pubmed/8896562
type: PublicationXref
id: 8896562
author: Saarialho-Kere, U
author: Haila, S
author: Kere, J
author: de la Chapelle, A
author: Socha, J
author: Karjalainen-Lindsberg, ML
author: Airola, K
author: Höglund, P
author: Tomaszewski, L
author: Holmberg, C
db: Pubmed
title: Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea
source: Nat Genet 14:316-9
year: 1996

UnificationXref3797
type: UnificationXref
id: 379786
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379786

UnificationXref3798
type: UnificationXref
id: REACT_17784
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_17784.1

UnificationXref3795
type: UnificationXref
id: REACT_15991
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15991.1

http://identifiers.org/pubmed/8618861
type: PublicationXref
id: 8618861
author: Nevins, JR
author: DeGregori, J
author: Ohtani, K
db: Pubmed
title: Regulation of the cyclin E gene by transcription factor E2F1
source: Proc Natl Acad Sci U S A 92:12146-50
year: 1995

UnificationXref3796
type: UnificationXref
id: CHEBI:29155
db: ChEBI

UnificationXref1650
type: UnificationXref
id: 5608194
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608194

UnificationXref3793
type: UnificationXref
id: CHEBI:29178
db: ChEBI

UnificationXref1651
type: UnificationXref
id: 5608195
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608195

UnificationXref3794
type: UnificationXref
id: 379758
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379758

UnificationXref1652
type: UnificationXref
id: 69599
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=69599

UnificationXref3791
type: UnificationXref
id: 5613576
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613576

UnificationXref1653
type: UnificationXref
id: REACT_2474
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2474.1

UnificationXref3792
type: UnificationXref
id: REACT_215894
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_215894.2

UnificationXref3790
type: UnificationXref
id: 5613574
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613574

Active PKC theta bound to DAG (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry567
component stoichiometry: Stoichiometry568
component: SmallMolecule76
component: Protein702
xref: UnificationXref2166
cellular location: GO_0005886
comment: Reactome DB_ID: 5612922

p-Y90-PKC-theta:DAG (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry564
component stoichiometry: Stoichiometry565
component: SmallMolecule76
component: Protein701
xref: UnificationXref2164
cellular location: GO_0005886
comment: Reactome DB_ID: 5612917

AKT:PIP3 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry571
component stoichiometry: Stoichiometry572
component: PhysicalEntity2
component: SmallMolecule11
xref: UnificationXref2176
cellular location: GO_0005886
comment: Reactome DB_ID: 5612612

PDPK1:PIP3 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry569
component stoichiometry: Stoichiometry570
component: Homologues of PDPK1
component: SmallMolecule11
xref: UnificationXref2173
cellular location: GO_0005886
comment: Reactome DB_ID: 5612532

TORC2 complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry577
component stoichiometry: Stoichiometry578
component stoichiometry: Stoichiometry575
component stoichiometry: Stoichiometry576
component: PhysicalEntity7
component: Protein710
component: Protein711
component: Protein707
xref: UnificationXref2194
cellular location: GO_0005829
comment: Reactome DB_ID: 5612617

p-S-AKT:PIP3 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry573
component stoichiometry: Stoichiometry574
component: SmallMolecule11
component: PhysicalEntity52
xref: UnificationXref2184
cellular location: GO_0005886
comment: Reactome DB_ID: 5612541

CDC42:GTP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry581
component stoichiometry: Stoichiometry582
component: Note: the coordinates are copied over from Homo sapiens.
component: SmallMolecule26
xref: UnificationXref2209
cellular location: GO_0005829
comment: Reactome DB_ID: 5613447

p-S-AKT:PDPK1:PIP3 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry579
component stoichiometry: Stoichiometry580
component: PDPK1:PIP3 (name copied from entity in Homo sapiens)
component: p-S-AKT:PIP3 (name copied from entity in Homo sapiens)
xref: UnificationXref2197
cellular location: GO_0005886
comment: Reactome DB_ID: 5612542

PAK bound to Rac1 and Cdc42 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry584
component stoichiometry: Stoichiometry585
component: CDC42:GTP (name copied from entity in Homo sapiens)
component: PhysicalEntity54
xref: UnificationXref2220
cellular location: GO_0005829
comment: Reactome DB_ID: 5613827

UnificationXref1655
type: UnificationXref
id: REACT_222108
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_222108.2

PAK1-3 dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry583
component: PhysicalEntity54
xref: UnificationXref2219
cellular location: GO_0005829
comment: Reactome DB_ID: 5613826

UnificationXref1654
type: UnificationXref
id: 5608196
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608196

UnificationXref1657
type: UnificationXref
id: 5608200
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608200

UnificationXref1656
type: UnificationXref
id: P38147
db: UniProt

UnificationXref1659
type: UnificationXref
id: P38110
db: UniProt

UnificationXref1658
type: UnificationXref
id: 5608211
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608211

UnificationXref3799
type: UnificationXref
id: P07263
db: UniProt

UnificationXref3784
type: UnificationXref
id: REACT_18164
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_18164.1

UnificationXref3785
type: UnificationXref
id: P38088
db: UniProt

UnificationXref3786
type: UnificationXref
id: 5613568
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613568

UnificationXref3787
type: UnificationXref
id: Q06817
db: UniProt

UnificationXref1641
type: UnificationXref
id: 5608191
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608191

UnificationXref3780
type: UnificationXref
id: 379766
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379766

UnificationXref1642
type: UnificationXref
id: 75807
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=75807

UnificationXref3781
type: UnificationXref
id: REACT_15638
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15638.1

UnificationXref3782
type: UnificationXref
id: CHEBI:29156
db: ChEBI

UnificationXref1640
type: UnificationXref
id: 5608189
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608189

UnificationXref3783
type: UnificationXref
id: 379784
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379784

PIP3:PDK1:active AKT (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry588
component stoichiometry: Stoichiometry586
component stoichiometry: Stoichiometry587
component: PhysicalEntity53
component: Homologues of PDPK1
component: SmallMolecule11
xref: UnificationXref2227
cellular location: GO_0005886
comment: Reactome DB_ID: 5613960

TAP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry606
component stoichiometry: Stoichiometry605
component: Protein755
component: Protein754
xref: UnificationXref2388
cellular location: GO_0030670
comment: Reactome DB_ID: 5615725

TAP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry601
component stoichiometry: Stoichiometry600
component: Protein752
component: Protein753
xref: UnificationXref2373
cellular location: GO_0005789
comment: Reactome DB_ID: 5615559

PDPK1:PIP2 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry596
component stoichiometry: Stoichiometry595
component: SmallMolecule77
component: Homologues of PDPK1
xref: UnificationXref2280
cellular location: GO_0005886
comment: Reactome DB_ID: 5616916

PP2A (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry590
component stoichiometry: Stoichiometry589
component stoichiometry: Stoichiometry591
component: Protein727
component: Protein733
component: Protein724
xref: UnificationXref2240
cellular location: GO_0005829
comment: Reactome DB_ID: 5613771

http://identifiers.org/pubmed/1756912
type: PublicationXref
id: 1756912
author: Morgan, R
author: Rees, A
author: Choi, WH
author: Moller, DE
author: O'Rahilly, S
author: Buse, JB
author: Flier, JS
db: Pubmed
title: Molecular scanning of insulin-responsive glucose transporter (GLUT4) gene in NIDDM subjects
source: Diabetes 40:1712-8
year: 1991

CDC42:GDP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry617
component stoichiometry: Stoichiometry616
component: SmallMolecule67
component: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref2525
cellular location: GO_0005829
comment: Reactome DB_ID: 5613765

AGE adducts:Peptide:AGER-1,2,3 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry615
component stoichiometry: Stoichiometry614
component: Protein782
component: AGE adducts:Peptide (name copied from entity in Homo sapiens)
xref: UnificationXref2520
cellular location: GO_0005886
comment: Reactome DB_ID: 5615195

http://identifiers.org/pubmed/9461603
type: PublicationXref
id: 9461603
author: Aguado, B
author: Campbell, RD
db: Pubmed
title: Characterization of a human lysophosphatidic acid acyltransferase that is encoded by a gene located in the class III region of the human major histocompatibility complex
source: J Biol Chem 273:4096-105
year: 1998

AGE adducts:Peptide (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry612
component stoichiometry: Stoichiometry613
component: SmallMolecule99
component: SmallMolecule100
xref: UnificationXref2519
cellular location: GO_0005576
comment: Reactome DB_ID: 5615185

SUGT1:HSP90 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry610
component stoichiometry: Stoichiometry611
component: Protein776
component: Protein779
xref: UnificationXref2486
cellular location: GO_0005829
comment: Reactome DB_ID: 5615182

UnificationXref1646
type: UnificationXref
id: P22216
db: UniProt

UnificationXref1645
type: UnificationXref
id: REACT_216627
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_216627.2

UnificationXref1644
type: UnificationXref
id: 5608193
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608193

CDC42-GTP:WASP/N-WASP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry620
component stoichiometry: Stoichiometry619
component stoichiometry: Stoichiometry618
component: SmallMolecule77
component: CDC42:GTP (name copied from entity in Homo sapiens)
component: Protein785
xref: UnificationXref2532
cellular location: GO_0005829
comment: Reactome DB_ID: 5614457

UnificationXref1643
type: UnificationXref
id: REACT_5826
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5826.1

UnificationXref3789
type: UnificationXref
id: 5613573
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613573

UnificationXref1649
type: UnificationXref
id: REACT_217637
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_217637.2

UnificationXref3788
type: UnificationXref
id: 5613572
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613572

UnificationXref1648
type: UnificationXref
id: 5608208
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608208

UnificationXref1647
type: UnificationXref
id: 5608206
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608206

UnificationXref816
type: UnificationXref
id: 5609194
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609194

SequenceSite910
type: SequenceSite
position status: EQUAL
sequence position: 1462

UnificationXref815
type: UnificationXref
id: P48589
db: UniProt

SequenceSite911
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref818
type: UnificationXref
id: 5609313
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609313

SequenceSite912
type: SequenceSite
position status: EQUAL
sequence position: 598

UnificationXref817
type: UnificationXref
id: P38711
db: UniProt

SequenceSite913
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref819
type: UnificationXref
id: P35997
db: UniProt

SequenceSite908
type: SequenceSite
position status: EQUAL
sequence position: 420

SequenceSite907
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref810
type: UnificationXref
id: P0CX48
db: UniProt

SequenceSite909
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref811
type: UnificationXref
id: 5609187
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609187

SequenceSite904
type: SequenceSite
position status: EQUAL
sequence position: 527

UnificationXref812
type: UnificationXref
id: P0CX47
db: UniProt

SequenceSite903
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref813
type: UnificationXref
id: 5609189
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609189

SequenceSite906
type: SequenceSite
position status: EQUAL
sequence position: 2286

UnificationXref814
type: UnificationXref
id: 5609190
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609190

SequenceSite905
type: SequenceSite
position status: EQUAL
sequence position: 1

UniProt:P28239
type: ProteinReference
name: PPA2
xref: UnificationXref3872
organism: http://identifiers.org/taxonomy/4932

UnificationXref807
type: UnificationXref
id: 5609220
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609220

SequenceSite901
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref806
type: UnificationXref
id: 5609219
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609219

SequenceSite902
type: SequenceSite
position status: EQUAL
sequence position: 560

http://identifiers.org/pubmed/18043707
type: PublicationXref
id: 18043707
author: Hamm, HE
author: Oldham, WM
db: Pubmed
title: Heterotrimeric G protein activation by G-protein-coupled receptors
source: Nat Rev Mol Cell Biol 9:60-71
year: 2008

UnificationXref805
type: UnificationXref
id: P0CX51
db: UniProt

UnificationXref804
type: UnificationXref
id: 5609217
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609217

SequenceSite900
type: SequenceSite
position status: EQUAL
sequence position: 2120

UnificationXref809
type: UnificationXref
id: 5609264
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609264

UnificationXref808
type: UnificationXref
id: P38701
db: UniProt

http://identifiers.org/pubmed/9295278
type: PublicationXref
id: 9295278
author: Krems, B
author: Casareno, R L
author: Culotta, V C
author: Gitlin, J D
author: Strain, J
author: Klomp, L W
db: Pubmed
title: The copper chaperone for superoxide dismutase
source: J. Biol. Chem. 272:23469-72
year: 1997

UnificationXref802
type: UnificationXref
id: 5609260
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609260

UnificationXref803
type: UnificationXref
id: P0CX52
db: UniProt

UnificationXref800
type: UnificationXref
id: 5609247
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609247

UnificationXref801
type: UnificationXref
id: P25443
db: UniProt

http://identifiers.org/pubmed/8755573
type: PublicationXref
id: 8755573
author: Webster, MK
author: Meyer, AN
author: Donoghue, DJ
author: Hart, KC
author: Galvin, BD
db: Pubmed
title: Constitutive receptor activation by Crouzon syndrome mutations in fibroblast growth factor receptor (FGFR)2 and FGFR2/Neu chimeras
source: Proc Natl Acad Sci U S A 93:7894-9
year: 1996

Active N-SMase:Mg2+ (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry700
component stoichiometry: Stoichiometry699
component: SmallMolecule116
component: Protein879
xref: UnificationXref2885
cellular location: GO_0005886
comment: Reactome DB_ID: 5612224

PIP3:RhoA (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry701
component stoichiometry: Stoichiometry702
component: SmallMolecule111
component: Protein880
xref: UnificationXref2908
cellular location: GO_0005886
comment: Reactome DB_ID: 5612937

ATP6V1G dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry693
component: Protein874
xref: UnificationXref2851
cellular location: GO_0005829
comment: Reactome DB_ID: 5610361

SequenceSite930
type: SequenceSite
position status: EQUAL
sequence position: 380

ATP6V1A trimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry696
component: Protein878
xref: UnificationXref2856
cellular location: GO_0005829
comment: Reactome DB_ID: 5610327

SequenceSite931
type: SequenceSite
position status: EQUAL
sequence position: 381

SequenceSite932
type: SequenceSite
position status: EQUAL
sequence position: 456

SequenceSite933
type: SequenceSite
position status: EQUAL
sequence position: 457

eNOS:CaM:HSP90:p-AKT1 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry716
component stoichiometry: Stoichiometry715
component: Protein888
component: eNOS:CaM:HSP90 (name copied from entity in Homo sapiens)
xref: UnificationXref2949
cellular location: GO_0005886
comment: Reactome DB_ID: 5612894

SequenceSite934
type: SequenceSite
position status: EQUAL
sequence position: 532

eNOS:CaM:HSP90 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry714
component stoichiometry: Stoichiometry713
component stoichiometry: Stoichiometry710
component: Active Calmodulin (name copied from entity in Homo sapiens)
component: palmitoylated, myristoylated eNOS dimer (name copied from entity in Homo sapiens)
component: Protein885
xref: UnificationXref2944
cellular location: GO_0005886
comment: Reactome DB_ID: 5612889

SequenceSite935
type: SequenceSite
position status: EQUAL
sequence position: 533

SequenceSite926
type: SequenceSite
position status: EQUAL
sequence position: 228

SequenceSite925
type: SequenceSite
position status: EQUAL
sequence position: 153

SequenceSite928
type: SequenceSite
position status: EQUAL
sequence position: 304

SequenceSite927
type: SequenceSite
position status: EQUAL
sequence position: 229

ATP6V1B trimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry688
component: Protein866
xref: UnificationXref2838
cellular location: GO_0005829
comment: Reactome DB_ID: 5610334

ATP6V1 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry692
component stoichiometry: Stoichiometry690
component stoichiometry: Stoichiometry691
component stoichiometry: Stoichiometry687
component stoichiometry: Stoichiometry697
component stoichiometry: Stoichiometry694
component stoichiometry: Stoichiometry689
component stoichiometry: Stoichiometry695
component: Protein873
component: ATP6V1B trimer (name copied from entity in Homo sapiens)
component: Protein872
component: Protein863
component: Protein877
component: ATP6V1G dimer (name copied from entity in Homo sapiens)
component: ATP6V1A trimer (name copied from entity in Homo sapiens)
component: Protein869
xref: UnificationXref2857
cellular location: GO_0005829
comment: Reactome DB_ID: 5610366

SequenceSite929
type: SequenceSite
position status: EQUAL
sequence position: 305

ATP6V0C hexamer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry680
component: Protein846
xref: UnificationXref2807
cellular location: endosome membrane
comment: Reactome DB_ID: 5610314

ATP6V0 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry681
component stoichiometry: Stoichiometry682
component stoichiometry: Stoichiometry683
component stoichiometry: Stoichiometry684
component stoichiometry: Stoichiometry679
component: Protein862
component: ATP6V0C hexamer (name copied from entity in Homo sapiens)
component: Protein859
component: PhysicalEntity69
component: PhysicalEntity70
xref: UnificationXref2829
cellular location: endosome membrane
comment: Reactome DB_ID: 5610322

UniProt:P22133
type: ProteinReference
name: MDH2
xref: UnificationXref6280
organism: http://identifiers.org/taxonomy/4932

UniProt:P22139 RPB10
type: ProteinReference
name: YOR210W
name: RPB10
xref: UnificationXref971
comment: MISCELLANEOUS Present with 5300 molecules/cell in log phase SD medium.SIMILARITY Belongs to the archaeal RpoN/eukaryotic RPB10 RNA polymerase subunit family.
organism: http://identifiers.org/taxonomy/4932

http://identifiers.org/pubmed/10781593
type: PublicationXref
id: 10781593
author: Kinoshita, T
author: Watanabe, R
author: Hong, Y
author: Maeda, Y
author: Inoue, N
author: Ohishi, K
db: Pubmed
title: Requirement of PIG-F and PIG-O for transferring phosphoethanolamine to the third mannose in glycosylphosphatidylinositol
source: J Biol Chem 275:20911-9
year: 2000

UniProt:P24279
type: ProteinReference
name: MCM3
xref: UnificationXref1560
organism: http://identifiers.org/taxonomy/4932

http://identifiers.org/pubmed/16182515
type: PublicationXref
id: 16182515
author: Hubbard, KB
author: Hepler, JR
db: Pubmed
title: Cell signalling diversity of the Gqalpha family of heterotrimeric G proteins
source: Cell Signal 18:135-50
year: 2006

SequenceSite920
type: SequenceSite
position status: EQUAL
sequence position: 76

SequenceSite923
type: SequenceSite
position status: EQUAL
sequence position: 77

SequenceSite924
type: SequenceSite
position status: EQUAL
sequence position: 152

SequenceSite921
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite922
type: SequenceSite
position status: EQUAL
sequence position: 76

SequenceSite917
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite916
type: SequenceSite
position status: EQUAL
sequence position: 76

SequenceSite915
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite914
type: SequenceSite
position status: EQUAL
sequence position: 861

SequenceSite919
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite918
type: SequenceSite
position status: EQUAL
sequence position: 76

http://identifiers.org/pubmed/21944752
type: PublicationXref
id: 21944752
author: Pierrel, F
author: Lill, R
author: Webert, H
author: Mühlenhoff, U
author: Fontecave, M
author: Ozeir, M
db: Pubmed
title: Coenzyme Q biosynthesis: Coq6 is required for the C5-hydroxylation reaction and substrate analogs rescue Coq6 deficiency
source: Chem Biol 18:1134-42
year: 2011

http://identifiers.org/pubmed/11470918
type: PublicationXref
id: 11470918
author: Wagner, H
author: Hausmann, S
author: Kirschning, CJ
author: Lipford, GB
author: Bauer, S
author: Redecke, V
author: Akira, S
author: Hacker, H
db: Pubmed
title: Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition
source: Proc Natl Acad Sci U S A 98:9237-42
year: 2001

UnificationXref859
type: UnificationXref
id: 5609291
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609291

SequenceSite955
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite954
type: SequenceSite
position status: EQUAL
sequence position: 863

SequenceSite957
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite956
type: SequenceSite
position status: EQUAL
sequence position: 821

SequenceSite951
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite950
type: SequenceSite
position status: EQUAL
sequence position: 734

SequenceSite953
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite952
type: SequenceSite
position status: EQUAL
sequence position: 719

http://identifiers.org/pubmed/11136247
type: PublicationXref
id: 11136247
author: Hurwitz, J
author: Lee, JK
db: Pubmed
title: Processive DNA helicase activity of the minichromosome maintenance proteins 4, 6, and 7 complex requires forked DNA structures
source: Proc Natl Acad Sci U S A 98:54-9
year: 2001

UnificationXref850
type: UnificationXref
id: Q3E754
db: UniProt

UnificationXref852
type: UnificationXref
id: P0C0V8
db: UniProt

UnificationXref851
type: UnificationXref
id: 5609268
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609268

UnificationXref854
type: UnificationXref
id: 5609273
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609273

UnificationXref853
type: UnificationXref
id: 5609272
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609272

UnificationXref856
type: UnificationXref
id: 5609288
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609288

SequenceSite947
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref855
type: UnificationXref
id: P0CX32
db: UniProt

SequenceSite948
type: SequenceSite
position status: EQUAL
sequence position: 904

UnificationXref858
type: UnificationXref
id: 5609290
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609290

SequenceSite949
type: SequenceSite
position status: EQUAL
sequence position: 1

http://identifiers.org/pubmed/10524214
type: PublicationXref
id: 10524214
author: Cregeen, DP
author: Rumsby, G
db: Pubmed
title: Identification and expression of a cDNA for human hydroxypyruvate/glyoxylate reductase
source: Biochim Biophys Acta 1446:383-8
year: 1999

UnificationXref857
type: UnificationXref
id: P0CX31
db: UniProt

SequenceSite946
type: SequenceSite
position status: EQUAL
sequence position: 560

SequenceSite945
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref848
type: UnificationXref
id: Q01855
db: UniProt

SequenceSite944
type: SequenceSite
position status: EQUAL
sequence position: 560

UnificationXref849
type: UnificationXref
id: 5609211
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609211

SequenceSite943
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite942
type: SequenceSite
position status: EQUAL
sequence position: 861

SequenceSite941
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite940
type: SequenceSite
position status: EQUAL
sequence position: 861

http://identifiers.org/pubmed/5666113
type: PublicationXref
id: 5666113
author: Luzzatto, L
author: Afolayan, A
db: Pubmed
title: Enzymic properties of different types of human erythrocyte glucose-6-phosphate dehydrogenase, with characterization of two new genetic variants
source: J Clin Invest 47:1833-42
year: 1968

http://identifiers.org/pubmed/16738407
type: PublicationXref
id: 16738407
author: Schotta, Gunnar
author: O'Sullivan, Roderick J
author: Kubicek, Stefan
author: Jenuwein, Thomas
author: Sengupta, Roopsha
author: Mechtler, Karl
author: Opravil, Susanne
author: Yonezawa, Masato
author: Fodor, Barna D
author: Perez-Burgos, Laura
db: Pubmed
title: Jmjd2b antagonizes H3K9 trimethylation at pericentric heterochromatin in mammalian cells
source: Genes Dev. 20:1557-62
year: 2006

UnificationXref843
type: UnificationXref
id: P0CX55
db: UniProt

UnificationXref842
type: UnificationXref
id: 5609359
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609359

UnificationXref841
type: UnificationXref
id: 5609358
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609358

UnificationXref840
type: UnificationXref
id: P23248
db: UniProt

UnificationXref847
type: UnificationXref
id: 5609238
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609238

SequenceSite938
type: SequenceSite
position status: EQUAL
sequence position: 684

UnificationXref846
type: UnificationXref
id: 5609237
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609237

SequenceSite939
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref845
type: UnificationXref
id: P0CX56
db: UniProt

SequenceSite936
type: SequenceSite
position status: EQUAL
sequence position: 608

UnificationXref844
type: UnificationXref
id: 5609235
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609235

SequenceSite937
type: SequenceSite
position status: EQUAL
sequence position: 609

SequenceSite973
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite972
type: SequenceSite
position status: EQUAL
sequence position: 1148

SequenceSite975
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite974
type: SequenceSite
position status: EQUAL
sequence position: 340

UnificationXref837
type: UnificationXref
id: 5609408
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609408

SequenceSite977
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref838
type: UnificationXref
id: P33442
db: UniProt

SequenceSite976
type: SequenceSite
position status: EQUAL
sequence position: 354

UnificationXref839
type: UnificationXref
id: 5609354
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609354

SequenceSite979
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite978
type: SequenceSite
position status: EQUAL
sequence position: 261

SequenceSite971
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite970
type: SequenceSite
position status: EQUAL
sequence position: 356

UnificationXref834
type: UnificationXref
id: 5609403
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609403

SequenceSite969
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref833
type: UnificationXref
id: O13516
db: UniProt

UnificationXref836
type: UnificationXref
id: 5609407
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609407

UnificationXref835
type: UnificationXref
id: P05755
db: UniProt

UnificationXref830
type: UnificationXref
id: 5609389
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609389

UnificationXref832
type: UnificationXref
id: 5609319
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609319

UnificationXref831
type: UnificationXref
id: 5609390
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609390

SequenceSite964
type: SequenceSite
position status: EQUAL
sequence position: 185

SequenceSite963
type: SequenceSite
position status: EQUAL
sequence position: 1

http://identifiers.org/pubmed/21413788
type: PublicationXref
id: 21413788
author: Dunaway-Mariano, Debra
author: Wu, Rui
author: Garland, Megan
author: Allen, Karen N
db: Pubmed
title: Homo sapiens dullard protein phosphatase shows a preference for the insulin-dependent phosphorylation site of lipin1
source: Biochemistry 50:3045-7
year: 2011

SequenceSite962
type: SequenceSite
position status: EQUAL
sequence position: 196

SequenceSite961
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref828
type: UnificationXref
id: 5609385
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609385

SequenceSite968
type: SequenceSite
position status: EQUAL
sequence position: 363

UnificationXref829
type: UnificationXref
id: P26786
db: UniProt

SequenceSite967
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref826
type: UnificationXref
id: 5609337
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609337

SequenceSite966
type: SequenceSite
position status: EQUAL
sequence position: 566

UnificationXref827
type: UnificationXref
id: P48164
db: UniProt

SequenceSite965
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite960
type: SequenceSite
position status: EQUAL
sequence position: 223

UnificationXref825
type: UnificationXref
id: 5609336
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609336

UnificationXref824
type: UnificationXref
id: P41057
db: UniProt

UnificationXref823
type: UnificationXref
id: 5609332
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609332

SequenceSite958
type: SequenceSite
position status: EQUAL
sequence position: 808

UnificationXref822
type: UnificationXref
id: P41058
db: UniProt

SequenceSite959
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref821
type: UnificationXref
id: 5609318
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609318

UnificationXref820
type: UnificationXref
id: 5609317
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5609317

http://identifiers.org/pubmed/21554866
type: PublicationXref
id: 21554866
author: Cox, Brian J
author: Biechele, Steffen
author: Rossant, Janet
db: Pubmed
title: Porcupine homolog is required for canonical Wnt signaling and gastrulation in mouse embryos
source: Dev. Biol. 355:275-85
year: 2011

SequenceSite110
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite111
type: SequenceSite
position status: EQUAL
sequence position: 227

SequenceSite112
type: SequenceSite
position status: EQUAL
sequence position: 1

Metabolism of carbohydrates
type: Pathway
data source: Provenance1
pathway component: REACT 245640.1
pathway component: REACT 230026.1
pathway component: REACT 233695.1
pathway component: REACT 233121.1
pathway component: Hexose transport
pathway component: REACT 227287.2
pathway component: REACT 232344.1
evidence: Evidence994
xref: RelationshipXref628
xref: UnificationXref6640
xref: UnificationXref6641
pathway order: PathwayStep961
pathway order: PathwayStep958
pathway order: PathwayStep975
pathway order: PathwayStep893
pathway order: PathwayStep978
pathway order: PathwayStep865
pathway order: PathwayStep904
display name: Carbohydrate metabolism
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

SequenceSite113
type: SequenceSite
position status: EQUAL
sequence position: 570

SequenceSite114
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite115
type: SequenceSite
position status: EQUAL
sequence position: 215

SequenceSite116
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite117
type: SequenceSite
position status: EQUAL
sequence position: 215

SequenceSite118
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite119
type: SequenceSite
position status: EQUAL
sequence position: 784

SequenceSite101
type: SequenceSite
position status: EQUAL
sequence position: 166

SequenceSite102
type: SequenceSite
position status: EQUAL
sequence position: 19

UniProt:P30822
type: ProteinReference
name: CRM1
xref: UnificationXref1805
organism: http://identifiers.org/taxonomy/4932

http://identifiers.org/pubmed/2351134
type: PublicationXref
id: 2351134
author: Finocchiaro, G
author: Colombo, I
author: Bloisi, W
author: Giardini, R
author: DiDonato, S
author: Garavaglia, B
db: Pubmed
title: Purification and properties of carnitine acetyltransferase from human liver
source: Eur J Biochem 189:539-46
year: 1990

SequenceSite100
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite105
type: SequenceSite
position status: EQUAL
sequence position: 654

http://identifiers.org/pubmed/19359157
type: PublicationXref
id: 19359157
author: Lykke-Andersen, J
author: Rebbapragada, I
db: Pubmed
title: Execution of nonsense-mediated mRNA decay: what defines a substrate?
source: Curr Opin Cell Biol 21:394-402
year: 2009

SequenceSite106
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite103
type: SequenceSite
position status: EQUAL
sequence position: 654

SequenceSite104
type: SequenceSite
position status: EQUAL
sequence position: 19

SequenceSite109
type: SequenceSite
position status: EQUAL
sequence position: 286

SequenceSite107
type: SequenceSite
position status: EQUAL
sequence position: 277

SequenceSite108
type: SequenceSite
position status: EQUAL
sequence position: 2

http://identifiers.org/pubmed/17698287
type: PublicationXref
id: 17698287
author: Grabowska, AM
author: Watson, SA
db: Pubmed
title: Role of gastrin peptides in carcinogenesis
source: Cancer Lett 257:1-15
year: 2007

SequenceSite132
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite133
type: SequenceSite
position status: EQUAL
sequence position: 790

SequenceSite134
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite135
type: SequenceSite
position status: EQUAL
sequence position: 105

SequenceSite130
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite131
type: SequenceSite
position status: EQUAL
sequence position: 898

SequenceSite136
type: SequenceSite
position status: EQUAL
sequence position: 2

http://identifiers.org/pubmed/7378348
type: PublicationXref
id: 7378348
author: So, AG
author: Tan, CK
author: Downey, KM
author: Lee, MY
db: Pubmed
title: Purification of deoxyribonucleic acid polymerase delta from calf thymus: partial characterization of physical properties.
source: Biochemistry 19:2096-101
year: 1980

SequenceSite137
type: SequenceSite
position status: EQUAL
sequence position: 105

SequenceSite138
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite139
type: SequenceSite
position status: EQUAL
sequence position: 105

http://identifiers.org/pubmed/22362766
type: PublicationXref
id: 22362766
author: Pallesen, Leif J
author: Walden, William E
author: Netz, Daili J A
author: Bill, Eckhard
author: Sharma, Anil K
author: Stümpfig, Martin
author: Lill, R
author: Pierik, Antonio J
db: Pubmed
title: A bridging [4Fe-4S] cluster and nucleotide binding are essential for function of the Cfd1-Nbp35 complex as a scaffold in iron-sulfur protein maturation
source: J. Biol. Chem. 287:12365-78
year: 2012

SequenceSite123
type: SequenceSite
position status: EQUAL
sequence position: 188

SequenceSite124
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite121
type: SequenceSite
position status: EQUAL
sequence position: 1865

SequenceSite122
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite120
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite129
type: SequenceSite
position status: EQUAL
sequence position: 2698

SequenceSite127
type: SequenceSite
position status: EQUAL
sequence position: 1056

SequenceSite128
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite125
type: SequenceSite
position status: EQUAL
sequence position: 1056

SequenceSite126
type: SequenceSite
position status: EQUAL
sequence position: 1

http://identifiers.org/pubmed/8089153
type: PublicationXref
id: 8089153
author: Hirst, M
author: Lou, L
author: Nakamura, J
author: Haliday, E
db: Pubmed
title: Human GMP synthetase. Protein purification, cloning, and functional expression of cDNA
source: J Biol Chem 269:23830-23837
year: 1994

S000001698
type: ProteinReference
name: UniProt:P28273
xref: UnificationXref10429
organism: http://identifiers.org/taxonomy/4932

URA1
type: ProteinReference
name: UniProt:P28272
xref: UnificationXref9436
organism: http://identifiers.org/taxonomy/4932

URA7
type: ProteinReference
name: UniProt:P28274
xref: UnificationXref9502
organism: http://identifiers.org/taxonomy/4932

SequenceSite159
type: SequenceSite
position status: EQUAL
sequence position: 213

SequenceSite158
type: SequenceSite
position status: EQUAL
sequence position: 402

http://identifiers.org/pubmed/18367721
type: PublicationXref
id: 18367721
author: Skinner, SJ
author: Deleault, KM
author: Whitfield, ML
author: Brooks, SA
author: Gross, RH
author: Townley-Tilson, WH
author: Emmons, J
db: Pubmed
title: Identification of TTP mRNA targets in human dendritic cells reveals TTP as a critical regulator of dendritic cell maturation
source: RNA 14:888-902
year: 2008

SequenceSite151
type: SequenceSite
position status: EQUAL
sequence position: 524

SequenceSite150
type: SequenceSite
position status: EQUAL
sequence position: 213

SequenceSite153
type: SequenceSite
position status: EQUAL
sequence position: 213

SequenceSite152
type: SequenceSite
position status: EQUAL
sequence position: 402

SequenceSite155
type: SequenceSite
position status: EQUAL
sequence position: 402

SequenceSite154
type: SequenceSite
position status: EQUAL
sequence position: 524

SequenceSite157
type: SequenceSite
position status: EQUAL
sequence position: 524

SequenceSite156
type: SequenceSite
position status: EQUAL
sequence position: 213

http://identifiers.org/pubmed/11425315
type: PublicationXref
id: 11425315
author: Peng, H
author: Liu, Q
author: Golde, DW
author: Vera, JC
db: Pubmed
title: The predicted ATP-binding domains in the hexose transporter GLUT1 critically affect transporter activity.
source: Biochemistry 40:7874-81
year: 2001

SequenceSite149
type: SequenceSite
position status: EQUAL
sequence position: 524

SequenceSite148
type: SequenceSite
position status: EQUAL
sequence position: 213

SequenceSite147
type: SequenceSite
position status: EQUAL
sequence position: 524

SequenceSite142
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite141
type: SequenceSite
position status: EQUAL
sequence position: 105

SequenceSite140
type: SequenceSite
position status: EQUAL
sequence position: 2

UniProt:P22023
type: ProteinReference
name: KRE5
xref: UnificationXref4962
organism: http://identifiers.org/taxonomy/4932

SequenceSite146
type: SequenceSite
position status: EQUAL
sequence position: 213

SequenceSite145
type: SequenceSite
position status: EQUAL
sequence position: 209

SequenceSite144
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite143
type: SequenceSite
position status: EQUAL
sequence position: 215

SequenceSite170
type: SequenceSite
position status: EQUAL
sequence position: 524

SequenceSite171
type: SequenceSite
position status: EQUAL
sequence position: 2

http://identifiers.org/pubmed/17635743
type: PublicationXref
id: 17635743
author: Bluteau, D
author: Debili, N
author: Chang, Y
author: Vainchenker, W
db: Pubmed
title: From hematopoietic stem cells to platelets
source: J Thromb Haemost 5:318-27
year: 2007

http://identifiers.org/pubmed/17686774
type: PublicationXref
id: 17686774
author: Tamura, A
author: Wakabayashi, K
author: Nakagawa, H
author: Hoshijima, K
author: Ishikawa, T
author: Komada, M
author: Koshiba, S
db: Pubmed
title: Intramolecular disulfide bond is a critical check point determining degradative fates of ATP-binding cassette (ABC) transporter ABCG2 protein
source: J Biol Chem 282:27841-6
year: 2007

beta-catenin independent WNT signaling
type: Pathway
data source: Provenance1
pathway component: REACT 187439.3
evidence: Evidence478
xref: UnificationXref3239
xref: UnificationXref3238
pathway order: PathwayStep470
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

SequenceSite177
type: SequenceSite
position status: EQUAL
sequence position: 197

SequenceSite176
type: SequenceSite
position status: EQUAL
sequence position: 192

SequenceSite179
type: SequenceSite
position status: EQUAL
sequence position: 524

SequenceSite178
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite173
type: SequenceSite
position status: EQUAL
sequence position: 19

SequenceSite172
type: SequenceSite
position status: EQUAL
sequence position: 524

SequenceSite175
type: SequenceSite
position status: EQUAL
sequence position: 55

SequenceSite174
type: SequenceSite
position status: EQUAL
sequence position: 20

Advanced glycosylation endproduct receptor signaling
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction162
evidence: Evidence328
xref: UnificationXref2524
xref: UnificationXref2523
pathway order: PathwayStep321
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

SequenceSite160
type: SequenceSite
position status: EQUAL
sequence position: 524

http://identifiers.org/pubmed/14521508
type: PublicationXref
id: 14521508
author: Fransson, A
author: Aspenstrom, P
author: Saras, J
db: Pubmed
title: Rho GTPases have diverse effects on the organization of the actin filament system
source: Biochem J 377:327-37
year: 2004

http://identifiers.org/pubmed/19261609
type: PublicationXref
id: 19261609
author: Vitvitsky, V
author: Singh, S
author: Banerjee, R
author: Zhu, W
author: Chiku, T
author: Padovani, D
db: Pubmed
title: H2S biogenesis by human cystathionine gamma-lyase leads to the novel sulfur metabolites lanthionine and homolanthionine and is responsive to the grade of hyperhomocysteinemia
source: J Biol Chem 284:11601-12
year: 2009

UniProt:P28241
type: ProteinReference
name: IDH2
xref: UnificationXref8988
organism: http://identifiers.org/taxonomy/4932

SequenceSite169
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite168
type: SequenceSite
position status: EQUAL
sequence position: 524

SequenceSite167
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite166
type: SequenceSite
position status: EQUAL
sequence position: 524

SequenceSite165
type: SequenceSite
position status: EQUAL
sequence position: 213

SequenceSite164
type: SequenceSite
position status: EQUAL
sequence position: 524

SequenceSite163
type: SequenceSite
position status: EQUAL
sequence position: 213

SequenceSite162
type: SequenceSite
position status: EQUAL
sequence position: 524

SequenceSite161
type: SequenceSite
position status: EQUAL
sequence position: 213

SequenceSite196
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref1544
type: UnificationXref
id: 5608143
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608143

SequenceSite197
type: SequenceSite
position status: EQUAL
sequence position: 736

UnificationXref1545
type: UnificationXref
id: 5608144
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608144

SequenceSite194
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref1546
type: UnificationXref
id: 5608145
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608145

SequenceSite195
type: SequenceSite
position status: EQUAL
sequence position: 736

UnificationXref1547
type: UnificationXref
id: REACT_28162
db: Reactome
id version: 5
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_28162.5

http://identifiers.org/pubmed/8428657
type: PublicationXref
id: 8428657
author: Yang, DC
author: Donovan, D
author: Vogeli, G
author: Vilalta, A
author: Wood, L
db: Pubmed
title: Cloning, sequencing and expression of a cDNA encoding mammalian valyl-tRNA synthetase
source: Gene 123:181-6
year: 1993

UnificationXref1548
type: UnificationXref
id: 5618006
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618006

UnificationXref1549
type: UnificationXref
id: REACT_245912
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_245912.1

http://identifiers.org/pubmed/16024644
type: PublicationXref
id: 16024644
author: Shimamura, T
author: Shapiro, GI
author: Engelman, JA
author: Lowell, AM
db: Pubmed
title: Epidermal growth factor receptors harboring kinase domain mutations associate with the heat shock protein 90 chaperone and are destabilized following exposure to geldanamycins
source: Cancer Res 65:6401-8
year: 2005

SequenceSite198
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite199
type: SequenceSite
position status: EQUAL
sequence position: 313

http://identifiers.org/pubmed/9268380
type: PublicationXref
id: 9268380
author: Fattaey, A
author: Booher, RN
author: Holman, PS
db: Pubmed
title: Human Myt1 is a cell cycle-regulated kinase that inhibits Cdc2 but not Cdk2 activity
source: J Biol Chem 272:22300-6
year: 1997

http://identifiers.org/pubmed/17222168
type: PublicationXref
id: 17222168
author: Agre, P
author: Frøkiaer, J
author: Nielsen, S
author: Kwon, TH
db: Pubmed
title: Regulation and dysregulation of aquaporins in water balance disorders
source: J Intern Med 261:53-64
year: 2007

SequenceSite193
type: SequenceSite
position status: EQUAL
sequence position: 524

UnificationXref1541
type: UnificationXref
id: 5608141
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608141

SequenceSite192
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref1540
type: UnificationXref
id: REACT_83036
db: Reactome
id version: 4
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_83036.4

SequenceSite191
type: SequenceSite
position status: EQUAL
sequence position: 197

UnificationXref1543
type: UnificationXref
id: REACT_243595
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_243595.1

SequenceSite190
type: SequenceSite
position status: EQUAL
sequence position: 192

UnificationXref1542
type: UnificationXref
id: 5608142
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608142

SequenceSite183
type: SequenceSite
position status: EQUAL
sequence position: 192

UnificationXref1557
type: UnificationXref
id: 5608120
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608120

SequenceSite184
type: SequenceSite
position status: EQUAL
sequence position: 197

UnificationXref1558
type: UnificationXref
id: P53091
db: UniProt

SequenceSite185
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref1555
type: UnificationXref
id: 5608132
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608132

SequenceSite186
type: SequenceSite
position status: EQUAL
sequence position: 524

UnificationXref1556
type: UnificationXref
id: P30665
db: UniProt

SequenceSite187
type: SequenceSite
position status: EQUAL
sequence position: 19

SequenceSite188
type: SequenceSite
position status: EQUAL
sequence position: 20

SequenceSite189
type: SequenceSite
position status: EQUAL
sequence position: 55

UnificationXref1559
type: UnificationXref
id: 5608128
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608128

http://identifiers.org/pubmed/17222174
type: PublicationXref
id: 17222174
author: Van Schaftingen, E
author: Linster, CL
db: Pubmed
title: Vitamin C: biosynthesis, recycling and degradation in mammals
source: FEBS J 274:1-22
year: 2007

UnificationXref1550
type: UnificationXref
id: P29469
db: UniProt

SequenceSite180
type: SequenceSite
position status: EQUAL
sequence position: 19

UnificationXref1554
type: UnificationXref
id: P38132
db: UniProt

UnificationXref1553
type: UnificationXref
id: 5608124
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608124

SequenceSite182
type: SequenceSite
position status: EQUAL
sequence position: 55

UnificationXref1552
type: UnificationXref
id: P29496
db: UniProt

SequenceSite181
type: SequenceSite
position status: EQUAL
sequence position: 20

UnificationXref1551
type: UnificationXref
id: 5608136
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608136

UnificationXref1566
type: UnificationXref
id: 5618004
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618004

UnificationXref1567
type: UnificationXref
id: REACT_241537
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_241537.1

UnificationXref1568
type: UnificationXref
id: 169515
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=169515

UnificationXref1569
type: UnificationXref
id: REACT_7812
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_7812.1

http://identifiers.org/pubmed/17320160
type: PublicationXref
id: 17320160
author: Bonni, Azad
author: Huarte, Maite
author: Iwase, Shigeki
author: Shi, Yang
author: Bayliss, Peter
author: Lan, Fei
author: Roberts, Thomas M
author: Qi, Hank H
author: Whetstine, Johnathan R
author: de la Torre-Ubieta, Luis
db: Pubmed
title: The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases
source: Cell 128:1077-88
year: 2007

http://identifiers.org/pubmed/11264579
type: PublicationXref
id: 11264579
author: Hutson, SM
author: Conway, ME
author: Dunbar, J
author: Farber, GK
author: Yennawar, NH
db: Pubmed
title: The structure of human mitochondrial branched-chain aminotransferase.
source: Acta Crystallogr D Biol Crystallogr 57:506-15
year: 2001

UnificationXref1563
type: UnificationXref
id: 5608146
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608146

UnificationXref1562
type: UnificationXref
id: 5608137
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608137

UnificationXref1565
type: UnificationXref
id: REACT_232020
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_232020.1

UnificationXref1564
type: UnificationXref
id: 5608147
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608147

UnificationXref1561
type: UnificationXref
id: 5608116
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608116

UnificationXref1560
type: UnificationXref
id: P24279
db: UniProt

UnificationXref1579
type: UnificationXref
id: 5611968
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611968

UnificationXref1577
type: UnificationXref
id: 5611964
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611964

UnificationXref1578
type: UnificationXref
id: P40359
db: UniProt

http://identifiers.org/pubmed/17320163
type: PublicationXref
id: 17320163
author: Yamane, Kenichi
author: Zhang, Yi
author: Yan, Qin
author: Kaelin, William G
author: Tempst, P
author: Klose, Robert J
author: Gilliland, D Gary
author: Erdjument-Bromage, H
author: Tothova, Zuzana
db: Pubmed
title: The retinoblastoma binding protein RBP2 is an H3K4 demethylase
source: Cell 128:889-900
year: 2007

http://identifiers.org/pubmed/17320161
type: PublicationXref
id: 17320161
author: Rappsilber, Juri
author: Cloos, Paul A C
author: Salcini, Anna Elisabetta
author: Hansen, Klaus H
author: Sennels, Lau
author: Pasini, Diego
author: Agger, Karl
author: Christensen, Jesper
author: Rose, Simon
author: Helin, Kristian
db: Pubmed
title: RBP2 belongs to a family of demethylases, specific for tri-and dimethylated lysine 4 on histone 3
source: Cell 128:1063-76
year: 2007

UnificationXref1576
type: UnificationXref
id: Q12488
db: UniProt

UnificationXref1575
type: UnificationXref
id: 5611972
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611972

UnificationXref1574
type: UnificationXref
id: Q03406
db: UniProt

UnificationXref1573
type: UnificationXref
id: REACT_258259
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_258259.1

UnificationXref1572
type: UnificationXref
id: 5611731
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611731

UnificationXref1571
type: UnificationXref
id: REACT_7610
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_7610.1

UnificationXref1570
type: UnificationXref
id: 169509
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=169509

http://identifiers.org/pubmed/18767960
type: PublicationXref
id: 18767960
author: Antonellis, A
author: Green, ED
db: Pubmed
title: The role of aminoacyl-tRNA synthetases in genetic diseases
source: Annu Rev Genomics Hum Genet 9:87-107
year: 2008

G-protein alpha:GDP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry770
component stoichiometry: Stoichiometry769
component: SmallMolecule67
component: Protein985
xref: UnificationXref3168
cellular location: GO_0005886
comment: Reactome DB_ID: 5611175

G protein alpha:GTP complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry767
component stoichiometry: Stoichiometry768
component: SmallMolecule26
component: Protein985
xref: UnificationXref3167
cellular location: GO_0005886
comment: Reactome DB_ID: 5611125

UnificationXref3809
type: UnificationXref
id: P15624
db: UniProt

Protein Kinase C, alpha type: DAG (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry774
component stoichiometry: Stoichiometry773
component: SmallMolecule14
component: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref3199
cellular location: GO_0005886
comment: Reactome DB_ID: 5614009

UnificationXref3808
type: UnificationXref
id: REACT_15573
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15573.1

Activated PLC beta 1/4 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry772
component stoichiometry: Stoichiometry771
component: Protein987
component: G protein alpha:GTP complex (name copied from entity in Homo sapiens)
xref: UnificationXref3179
cellular location: GO_0005886
comment: Reactome DB_ID: 5611126

UnificationXref3807
type: UnificationXref
id: 379792
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379792

UnificationXref1589
type: UnificationXref
id: 5608155
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608155

VPS35:VPS29:VPS26 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry776
component stoichiometry: Stoichiometry778
component stoichiometry: Stoichiometry777
component: Protein994
component: Protein993
component: Protein995
xref: UnificationXref3217
cellular location: GO_0005829
comment: Reactome DB_ID: 5617387

UnificationXref3806
type: UnificationXref
id: CHEBI:29153
db: ChEBI

http://identifiers.org/pubmed/2995985
type: PublicationXref
id: 2995985
author: Evans, DR
author: Kelly, RE
author: Pastra-Landis, SC
author: Lee, L
db: Pubmed
title: Oligomeric structure of the multifunctional protein CAD that initiates pyrimidine biosynthesis in mammalian cells
source: Proc Natl Acad Sci USA 82:6802-6806
year: 1985

UnificationXref1588
type: UnificationXref
id: P40348
db: UniProt

WLS:retromer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry775
component stoichiometry: Stoichiometry779
component stoichiometry: Stoichiometry780
component: PhysicalEntity74
component: VPS35:VPS29:VPS26 (name copied from entity in Homo sapiens)
component: Protein992
xref: UnificationXref3219
cellular location: GO_0031901
comment: Reactome DB_ID: 5617393

UnificationXref3805
type: UnificationXref
id: REACT_17850
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_17850.1

activated PKC alpha (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry785
component stoichiometry: Stoichiometry788
component stoichiometry: Stoichiometry787
component stoichiometry: Stoichiometry786
component: SmallMolecule20
component: SmallMolecule14
component: SmallMolecule9
component: Protein996
xref: UnificationXref3226
cellular location: GO_0005886
comment: Reactome DB_ID: 5617682

UnificationXref3804
type: UnificationXref
id: 379767
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379767

WLS:retromer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry783
component stoichiometry: Stoichiometry782
component stoichiometry: Stoichiometry781
component: PhysicalEntity25
component: VPS35:VPS29:VPS26 (name copied from entity in Homo sapiens)
component: Protein992
xref: UnificationXref3220
cellular location: GO_0000139
comment: Reactome DB_ID: 5617394

UnificationXref3803
type: UnificationXref
id: CHEBI:29184
db: ChEBI

http://identifiers.org/pubmed/6022858
type: PublicationXref
id: 6022858
author: Younathan, ES
author: Pynes, GD
db: Pubmed
title: Purification and some properties of inorganic pyrophosphatase from human erythrocytes
source: J Biol Chem 242:2119-23
year: 1967

pT298-NLK dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry790
component: Protein998
xref: UnificationXref3233
cellular location: GO_0005654
comment: Reactome DB_ID: 5617691

UnificationXref3802
type: UnificationXref
id: REACT_220687
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_220687.2

pT298-NLK dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry789
component: Protein997
xref: UnificationXref3231
cellular location: GO_0005829
comment: Reactome DB_ID: 5617689

UnificationXref3801
type: UnificationXref
id: 5613500
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613500

UnificationXref3800
type: UnificationXref
id: 5613498
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613498

UnificationXref1580
type: UnificationXref
id: 5611973
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611973

UnificationXref1581
type: UnificationXref
id: Q08032
db: UniProt

UnificationXref1582
type: UnificationXref
id: 5607913
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5607913

Evidence498
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8330735
xref: http://identifiers.org/pubmed/8946909
comment: Although TBP (TATA box binding factor) is necessary and sufficient for initiation of basal transcription, the other subunits of the general transcription factor TFIID, the TBP-associated factors, are required for response to transcriptional activators. TBP binds to the TATA box (a core promoter element), and bends the DNA 80 degrees toward the major groove. This conformation of TBP-TATA box provides the proper topology for the binding of the general transcription factor TFIIB. Transcriptional activators function by affecting the kinetics of binding of TBP to the promoter DNA.

UnificationXref1583
type: UnificationXref
id: 5611974
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611974

Evidence499
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8946909
comment: The general transcription factor TFIIB is a single polypeptide of approximately 35 kDa. There is a Zn-binding domain near the N terminus of TFIIB, and the C-terminal domain encompasses two imperfect repeats; between the N and C termini is a phylogenetically conserved region. The C terminus interacts with TBP and RNA Polymerase II, whereas the N terminus interacts with factor TFIIF and RNA polymerase II. TFIIB is a sequence-specific factor, and it interacts with the BRE element within the promoter. TFIIB interacts with the Rpb1 subunit of RNA polymerase II to define transcription strat sites. Several activators directly bind TFIIB, and stimulate transcription. The N-terminus and the C-terminus can participate in intramolecular interactions, and this can be disrupted by specific activators by causing a conformational change in TFIIB. TFIIA also binds the preinitiation complex along with TFIIB. However, TFIIA is not required for accurate initiation, but rather functions as a coactivator of transcription.

UnificationXref1584
type: UnificationXref
id: 5611975
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611975

http://identifiers.org/pubmed/18201392
type: PublicationXref
id: 18201392
author: Clarke, LA
db: Pubmed
title: The mucopolysaccharidoses: a success of molecular medicine
source: Expert Rev Mol Med 10:e1
year: 2008

UnificationXref1585
type: UnificationXref
id: REACT_242774
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_242774.1

UnificationXref1586
type: UnificationXref
id: 5618309
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618309

UnificationXref1587
type: UnificationXref
id: REACT_255883
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_255883.1

Evidence492
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17937601
xref: http://identifiers.org/pubmed/20198122
xref: http://identifiers.org/pubmed/21622208
xref: http://identifiers.org/pubmed/22249808
xref: http://identifiers.org/pubmed/19724019
xref: http://identifiers.org/pubmed/21713385
xref: http://identifiers.org/pubmed/20600241
xref: http://identifiers.org/pubmed/20553370
xref: http://identifiers.org/pubmed/21527729
xref: http://identifiers.org/pubmed/23579596
xref: http://identifiers.org/pubmed/23565489
xref: http://identifiers.org/pubmed/22448029
xref: http://identifiers.org/pubmed/21489811
xref: http://identifiers.org/pubmed/21147620
xref: http://identifiers.org/pubmed/22211890
xref: http://identifiers.org/pubmed/23562747
xref: http://identifiers.org/pubmed/21331644
xref: http://identifiers.org/pubmed/22991412
xref: http://identifiers.org/pubmed/22289780
xref: http://identifiers.org/pubmed/22458591
xref: http://identifiers.org/pubmed/21677426
xref: http://identifiers.org/pubmed/20029269
comment: Leptin (LEP, OB, OBS), a circulating adipokine, and its receptor LEPR (DB, OBR) control food intake and energy balance and are implicated in obesity-related diseases (recently reviewed in Amitani et al. 2013, Dunmore and Brown 2013, Cottrell and Mercer 2012, La Cava 2012, Marroqui et al. 2012, Paz-Filho et al. 2012, Denver et al. 2011, Lee 2011, Marino et al. 2011, Morton and Schwartz 2011, Scherer and Buettner 2011, Shan and Yeo 2011, Wauman and Tavernier 2011, Dardeno et al. 2010, Bjorbaek 2009, Morris and Rui 2009, Myers et al. 2008), including cancer (Guo et al. 2012), inflammation (Newman and Gonzalez-Perez 2013, Iikuni et al. 2008), and angiogenesis (Gonzalez-Perez et al. 2013). The identification of spontaneous mutations in the leptin gene (ob or LEP) and the leptin receptor gene (Ob-R, db or LEPR) genes in mice opened up a new field in obesity research. Leptin was discovered as the product of the gene affected by the ob (obesity) mutation, which causes obesity in mice. Likewise LEPR is the product of the gene affected by the db (diabetic) mutation. Leptin binding to LEPR induces canonical (JAK2/STATs; MAPK/ERK 1/2, PI-3K/AKT) and non-canonical signaling pathways (PKC, JNK, p38 MAPK and AMPK) in diverse cell types. The binding of leptin to the long isoform of LEPR (OB-Rl) initiates a phosphorylation cascade that results in transcriptional activation of target genes by STAT5 and STAT3 and activation of the PI3K pathway(not shown here), the MAPK/ERK pathway, and the mTOR/S6K pathway. Shorter LEPR isoforms with truncated intracellular domains are unable to activate the STAT pathway, but can transduce signals by way of activation of JAK2, IRS-1 or ERKs, including MAPKs. LEPR is constitutively bound to the JAK2 kinase. Binding of LEP to LEPR causes a conformational change in LEPR that activates JAK2 autophosphorylation followed by phosphorylation of LEPR by JAK2. Phosphorylated LEPR binds STAT3, STAT5, and SHP2 which are then phosphorylated by JAK2. Phosphorylated…

Evidence493
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/21781017
xref: http://identifiers.org/pubmed/18483217
xref: http://identifiers.org/pubmed/16939974
xref: http://identifiers.org/pubmed/21252999
xref: http://identifiers.org/pubmed/19379690
xref: http://identifiers.org/pubmed/15450248
xref: http://identifiers.org/pubmed/17084981
xref: http://identifiers.org/pubmed/19648010
xref: http://identifiers.org/pubmed/19762341
xref: http://identifiers.org/pubmed/17604717
xref: http://identifiers.org/pubmed/19536106
xref: http://identifiers.org/pubmed/19458711
xref: http://identifiers.org/pubmed/15863030
xref: http://identifiers.org/pubmed/19935667
xref: http://identifiers.org/pubmed/11742412
xref: http://identifiers.org/pubmed/19619488
xref: http://identifiers.org/pubmed/18043707
xref: http://identifiers.org/pubmed/17496910
xref: http://identifiers.org/pubmed/15520807
xref: http://identifiers.org/pubmed/16260143
comment: Signal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such as hormones and growth factors, or reacting to other types of stimuli, such as light. Stimulation of transmembrane receptors leads to their conformational change which propagates the signal to the intracellular environment by activating downstream signaling cascades. Depending on the cellular context, this may impact cellular proliferation, differentiation, and survival. On the organism level, signal transduction regulates overall growth and behavior. Receptor tyrosine kinases (RTKs) transmit extracellular signals by phosphorylating their protein partners on conserved tyrosine residues. Some of the best studied RTKs are EGFR (reviewed in Avraham and Yarden, 2011), FGFR (reviewed in Eswarakumar et al, 2005), insulin receptor (reviewed in Saltiel and Kahn, 2001), NGF (reviewed in Reichardt, 2006), PDGF (reviewed in Andrae et al, 2008) and VEGF (reviewed in Xie et al, 2004). RTKs frequently activate downstream signaling through RAF/MAP kinases (reviewed in McKay and Morrison, 2007 and Wellbrock et al 2004), AKT (reviewed in Manning and Cantley, 2007) and PLC- gamma (reviewed in Patterson et al), which ultimately results in changes in gene expression and cellular metabolism. Receptor serine/threonine kinases of the TGF-beta family, such as TGF-beta receptors (reviewed in Kang et al. 2009) and BMP receptors (reviewed in Miyazono et al. 2009), transmit extracellular signals by phosphorylating regulatory SMAD proteins on conserved serine and threonine residues. This leads to formation of complexes of regulatory SMADs and SMAD4, which translocate to the nucleus where they act as transcription factors. WNT receptors transmit their signal through beta-catenin. In the absence of ligand, beta-catenin is constitutively degraded in a ubiquitin-dependent manner. WNT receptor stimulation…

Evidence490
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/20430952
xref: http://identifiers.org/pubmed/22658984
xref: http://identifiers.org/pubmed/20192770
comment: The visual pigment (rhodopsin in rods) consists of an 11-cis-retinal (11cRAL) chromophore covalently attached to a GPCR opsin family member via a Schiff base linkage. Upon photon absorption, 11cRAL isomerizes to all trans retinal (atRAL), changing the conformation of opsin to a form that can activate the regulatory G protein transducin (Gt). The alpha subunit of Gt activates phosphodiesterase which hydrolyses cGMP to 5'-GMP. A high level of cGMP keeps cGMP-gated cation channels open, so lower cGMP levels close these channels and hyperpolarize the cell. The hyperpolarization spreads passively to the synapse located at the opposite end of the rod, where it subsequently closes voltage-gated calcium channels. Vesicular release of the neurotransmitter glutamate subsides as the intracellular calcium levels drop. This diminution of neurotransmitter release relays the light signal to postsynaptic neurons. The events below describe activation, inactivation, recovery and regulation of the phototransduction cascade in rods (Burns & Pugh 2010, Korenbrot 2012, Smith 2010).

Evidence491
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/22074927
xref: http://identifiers.org/pubmed/16688755
xref: http://identifiers.org/pubmed/21111842
xref: http://identifiers.org/pubmed/20188572
xref: http://identifiers.org/pubmed/16011460
xref: http://identifiers.org/pubmed/22074928
xref: http://identifiers.org/pubmed/15384919
xref: http://identifiers.org/pubmed/11340090
xref: http://identifiers.org/pubmed/20430952
xref: http://identifiers.org/pubmed/22658984
xref: http://identifiers.org/pubmed/21350678
xref: http://identifiers.org/pubmed/8382952
comment: Visual phototransduction is the process by which photon absorption by visual pigment molecules in photoreceptor cells is converted to an electrical cellular response. The events in this process are photochemical, biochemical and electrophysiological and are highly conserved across many species. This process occurs in two types of photoreceptors in the retina, rods and cones. Each type consists of two parts, the outer segment which detects a photon signal and the inner segment which contains the necessary machinery for cell metabolism. Each type of cell functions differently. Rods are very light sensitive but their flash response is slow so they work best in twilight conditions but are not good at detecting objects moving quickly. Cones are less light-sensitive and have a fast flash response so they work best in daylight conditions and are better at detecting fast moving objects than rods. The visual pigment consists of a chromophore (11-cis-retinal, 11cRAL, A1) covalently attached to a GPCR opsin family member. The linkage is via a Schiff base forming retinylidene protein. Upon photon absorption, 11cRAL isomerises to all-trans retinal (atRAL), changing the conformation of opsin to an activated form which can activate the regulatory G protein transducin (Gt). The alpha subunit of Gt activates phosphodiesterase which hydrolyses cGMP to 5'-GMP. As high level of cGMP keep cGMP-gated sodium channels open, the lowering of cGMP levels closes these channels which causes hyperpolarization of the cell and subsequently, closure of voltage-gated calcium channels. As calcium levels drop, the level of the neurotransmitter glutamate also drops causing depolarization of the cell. This effectively relays the light signal to postsynaptic neurons as electrical signal (Burns & Pugh 2010, Korenbrot 2012, Pugh & Lamb 1993). 11cRAL cannot be synthesised in vertebrates. Vitamin A from many dietary sources is the precursor for 11cRAL. It is taken from food in the form of esters such as reti…

Evidence496
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/2449431
comment: At the beginning of this reaction, 1 molecule of 'pol II open pre-initiation complex' is present. At the end of this reaction, 1 molecule of 'pol II closed pre-initiation complex' is present. This reaction takes place in the 'nucleus'.

Evidence494
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: At the beginning of this reaction, 1 molecule of 'SUPT5H protein', and 1 molecule of 'SPT4H1 protein' are present. At the end of this reaction, 1 molecule of 'DSIF complex' is present. This reaction takes place in the 'nucleus'.

Evidence495
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: At the beginning of this reaction, 1 molecule of 'FACT 140 kDa subunit', and 1 molecule of 'FACT 80 kDa subunit' are present. At the end of this reaction, 1 molecule of 'FACT complex' is present. This reaction takes place in the 'nucleus'.

RhoGTPase:GDP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry750
component stoichiometry: Stoichiometry751
component: Protein969
component: SmallMolecule67
xref: UnificationXref3117
cellular location: GO_0005829
comment: Reactome DB_ID: 5612313

UnificationXref3819
type: UnificationXref
id: CHEBI:29162
db: ChEBI

Inactivated RhoGTPase:GDP:GDI complex (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry749
component stoichiometry: Stoichiometry752
component: RhoGTPase:GDP (name copied from entity in Homo sapiens)
component: Protein963
xref: UnificationXref3118
cellular location: GO_0005829
comment: Reactome DB_ID: 5612314

UnificationXref3818
type: UnificationXref
id: REACT_16106
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_16106.1

RhoGTPase:GTP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry748
component stoichiometry: Stoichiometry747
component: Protein913
component: SmallMolecule120
xref: UnificationXref3042
cellular location: GO_0005886
comment: Reactome DB_ID: 5612316

DNA Damage Bypass
type: Pathway
data source: Provenance1
pathway component: REACT 243860.1
evidence: Evidence1780
xref: UnificationXref11484
xref: UnificationXref11485
pathway order: PathwayStep1760
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

p(S27)-G protein alpha (z):GTP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry760
component stoichiometry: Stoichiometry759
component: SmallMolecule120
component: Protein983
xref: UnificationXref3141
cellular location: GO_0005886
comment: Reactome DB_ID: 5615171

UnificationXref3815
type: UnificationXref
id: REACT_204382
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_204382.2

G-protein alpha (z):GTP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry757
component stoichiometry: Stoichiometry758
component: Protein981
component: SmallMolecule120
xref: UnificationXref3139
cellular location: GO_0005886
comment: Reactome DB_ID: 5613980

UnificationXref3814
type: UnificationXref
id: 5613511
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613511

G-protein alpha (i):GDP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry756
component stoichiometry: Stoichiometry755
component: Protein979
component: SmallMolecule119
xref: UnificationXref3134
cellular location: GO_0005886
comment: Reactome DB_ID: 5613986

UnificationXref3817
type: UnificationXref
id: 379762
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379762

G-protein alpha (i): GTP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry754
component stoichiometry: Stoichiometry753
component: Protein979
component: SmallMolecule120
xref: UnificationXref3133
cellular location: GO_0005886
comment: Reactome DB_ID: 5613985

UnificationXref1599
type: UnificationXref
id: 5608169
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608169

UnificationXref3816
type: UnificationXref
id: CHEBI:29179
db: ChEBI

UnificationXref3811
type: UnificationXref
id: P15625
db: UniProt

2-Hexaprenyl-6-methoxyphenol [ChEBI:1109]
type: SmallMoleculeReference
name: 2-Hexaprenyl-6-methoxyphenol
xref: UnificationXref874

RhoA/B/C:GTP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry766
component stoichiometry: Stoichiometry765
component: Protein984
component: SmallMolecule120
xref: UnificationXref3154
cellular location: GO_0005886
comment: Reactome DB_ID: 5614035

UnificationXref3810
type: UnificationXref
id: 5613508
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613508

RhoA,B,C:GDP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry764
component stoichiometry: Stoichiometry763
component: SmallMolecule119
component: Protein984
xref: UnificationXref3153
cellular location: GO_0005886
comment: Reactome DB_ID: 5614034

UnificationXref3813
type: UnificationXref
id: 5613509
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613509

G-protein alpha (z):GDP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry762
component stoichiometry: Stoichiometry761
component: Protein981
component: SmallMolecule119
xref: UnificationXref3145
cellular location: GO_0005886
comment: Reactome DB_ID: 5613981

UnificationXref3812
type: UnificationXref
id: 5613504
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613504

UnificationXref1593
type: UnificationXref
id: 5608167
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608167

Evidence487
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17114291
xref: http://identifiers.org/pubmed/7644482
xref: http://identifiers.org/pubmed/16274222
xref: http://identifiers.org/pubmed/17636946
comment: All eukaryotic proteins synthesized in the cytosol are initiated by methionine (Met). For the maturation of many proteins, the removal of N-terminal Met is essential and is mediated by methionine-aminopeptidases (METAPs). In human, there are two forms, METAP1 and 2 (Arfin et al. 1995). These enzymes utilise 2 cobalt ions (Co2+) as cofactors (Addlagatta et al. 2005, Hu et al. 2006, Marino et al. 2007).

http://identifiers.org/pubmed/1335363
type: PublicationXref
id: 1335363
author: Birnbaumer, L
db: Pubmed
title: Receptor-to-effector signaling through G proteins: roles for beta gamma dimers as well as alpha subunits
source: Cell 71:1069-72
year: 1992

UnificationXref1594
type: UnificationXref
id: P38629
db: UniProt

Evidence488
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9506952
xref: http://identifiers.org/pubmed/3006923
xref: http://identifiers.org/pubmed/9353336
comment: After removal of the N-terminal methionine (Met) residue, the enzymes glycylpeptide N-tetradecanoyltransferase 1 and 2 (NMT1 and 2) mediate the transfer of the myristoyl (MYS) group from myristoyl-CoA to the now N-terminal glycine (Gly) residue of transducin's alpha subunit (GNAT1) (Glover et al. 1997, Giang & Cravatt 1998). Myristoylation is thought to aid enzyme function and localization. Evidence from chicken experiments suggest non-myristoylated proteins do not bind to membranes (Kamps et al. 1986).

UnificationXref1591
type: UnificationXref
id: 5608159
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608159

Evidence489
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/20430952
xref: http://identifiers.org/pubmed/22658984
comment: To terminate the single photon response and restore the system to its basal state, the three activated intermediates in phototransduction, rhodopsin (MII), transducin alpha subunit with GTP bound (GNAT1-GTP) and phosphodiesterase 6 (PDE6) all need to be efficiently deactivated. In addition, the cGMP concentrations must be restored to support reopening of the CNG channels. This section describes the inactivation and recovery events of the activated intermediates involved in phototransduction (Burns & Pugh 2010, Korenbrot 2012).

UnificationXref1592
type: UnificationXref
id: P38630
db: UniProt

UnificationXref1597
type: UnificationXref
id: 5608163
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608163

GPVI-mediated activation cascade
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction4
pathway component: BiochemicalReaction5
pathway component: BiochemicalReaction6
evidence: Evidence12
xref: UnificationXref115
xref: UnificationXref114
pathway order: PathwayStep10
pathway order: PathwayStep11
pathway order: PathwayStep9
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref1598
type: UnificationXref
id: 5608168
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608168

UnificationXref1595
type: UnificationXref
id: 5608151
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608151

UnificationXref1596
type: UnificationXref
id: P40339
db: UniProt

Evidence480
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17598937
xref: http://identifiers.org/pubmed/18927274
xref: http://identifiers.org/pubmed/22649417
xref: http://identifiers.org/pubmed/20098959
xref: http://identifiers.org/pubmed/20975071
comment: Phosphorylated IGF1R binds and phosphorylates SHC1 (reviewed in Pavelic et al. 2007, Chitnis et al. 2008, Maki et al. 2010, Parrella et al. 2010, Siddle et al. 2012). Phosphorylated SHC then binds GRB:SOS, which activates RAS-RAF-MAPK signaling.

Evidence481
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17598937
xref: http://identifiers.org/pubmed/18927274
xref: http://identifiers.org/pubmed/22649417
xref: http://identifiers.org/pubmed/20098959
xref: http://identifiers.org/pubmed/20975071
xref: http://identifiers.org/pubmed/21042815
comment: The phosphorylated type 1 insulin-like growth factor receptor phosphorylates IR1, IRS2, IRS4 and possibly other IRS/DOK family members (reviewed in Pavelic et al. 2007, Chitnis et al. 2008, Maki et al. 2010, Parrella et al. 2010, Siddle et al. 2012). The phosphorylated IRS proteins serve as scaffolds that bind the effector molecules PI3K and GRB2:SOS. PI3K then activates PKB (AKT) signaling while GRB2:SOS activates RAS-RAF-MAPK signaling.

Evidence482
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17598937
xref: http://identifiers.org/pubmed/18927274
xref: http://identifiers.org/pubmed/22649417
xref: http://identifiers.org/pubmed/20098959
xref: http://identifiers.org/pubmed/20975071
xref: http://identifiers.org/pubmed/21042815
comment: After autophosphorylation the type 1 insulin-like growth factor receptor (IGF1R) binds and phosphorylates scaffold proteins, IRS1/2/4 and SHC1, which in turn bind effectors possessing enzymatic activity (recently reviewed in Pavelic et al. 2007, Chitnis et al. 2008, Maki et al. 2010, Parrella et al. 2010, and Siddle et al. 2012). IRS1/2/4 can bind both PI3K (via the p85 subunit of PI3K) and the GRB2:SOS complex. PI3K activates PKB (AKT, AKT1) signaling. GRB:SOS stimulates RAS to exchange GDP for GTP leading to activation of RAF and MAPK.

Evidence483
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/22044904
xref: http://identifiers.org/pubmed/17598937
xref: http://identifiers.org/pubmed/18927274
xref: http://identifiers.org/pubmed/22649417
xref: http://identifiers.org/pubmed/20098959
xref: http://identifiers.org/pubmed/20975071
xref: http://identifiers.org/pubmed/21042815
comment: Binding of IGF1 (IGF-I) or IGF2 (IGF-II) to the extracellular alpha peptides of the type 1 insulin-like growth factor receptor (IGF1R) triggers the activation of two major signaling pathways: the SOS-RAS-RAF-MAPK (ERK) pathway and the PI3K-PKB (AKT) pathway (recently reviewed in Pavelic et al. 2007, Chitnis et al. 2008, Maki et al. 2010, Parella et al. 2010, Annunziata et al. 2011, Siddle et al. 2012, Holzenberger 2012).

UnificationXref1590
type: UnificationXref
id: P38251
db: UniProt

Evidence484
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15949819
xref: http://identifiers.org/pubmed/9778132
xref: http://identifiers.org/pubmed/14634025
xref: http://identifiers.org/pubmed/14611934
xref: http://identifiers.org/pubmed/11756445
xref: http://identifiers.org/pubmed/16527816
comment: The outer segment of photoreceptor cells is shed every 10-14 days to be completely replaced. The shed material is phagocytosed and transferred to the retinal pigment epithelium (RPE). Diretinoid-pyridinium-phosphatidylethanolamine (A2PE) can be hydrolysed to diretinoid-pyridinium-ethanolamine (A2E), a prominent constituent of lipofuscin (the material deposited in retinal tissue which accumulates over time and is implicated in macular degeneration). Evidence suggests this happens before transfer to RPE cells as part of the phagocytosed outer segment. A2E has been detected in outer segments (Ben-Shabat et al. 2002) and an N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (NAPEPLD) activity detected in rat, mouse and human proteins (Okamoto et al. 2004, Ueda et al. 2005, Wang et al. 2006). This activity has been shown to hydrolyse A2PE to A2E in bovine outer segments before phagocytosis and transfer to RPE cells, suggesting A2PE is hydrolysed to A2E in photoreceptor outer segment membranes (Sparrow et al. 2003, Salvador & Giusto 1998).

Signaling by the B Cell Receptor (BCR)
type: Pathway
data source: Provenance1
pathway component: Downstream signaling events of B Cell Receptor (BCR)
evidence: Evidence286
xref: UnificationXref2288
xref: UnificationXref2287
pathway order: PathwayStep279
display name: B Cell Activation
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

Evidence485
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/20134024
xref: http://identifiers.org/pubmed/19666736
xref: http://identifiers.org/pubmed/22209824
comment: Lipofuscin is a yellow-brown pigment grain composed mainly of lipids but also sugars and certain metals. Accumulation of lipofuscin is associated with degenerative diseases such as Alzheimer's disease, Parkinson's disease, chronic obstructive pulmonary disease and retinal macular degeneration. A prominent component of lipofuscin in retinal pigment epithelial (RPE) cells is the bisretinoid A2E (di-retinoid-pyridinium-ethanolamine), the end-product of the condensation of 2 molecules of all-trans-retinal (atRAL) and phosphatidylethanolamine (PE) in photoreceptor outer disc membranes. Once formed, A2E is phagocytosed, together with outer segments (Kevany & Palczewski 2010), to RPE where it accumulates. There is no evidence as yet to indicate that A2E can be catabolised (Sparrow et al. 2012, Sparrow et al. 2010). A simplified biosynthetic pathway for A2E is described here.

Evidence486
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/22074927
xref: http://identifiers.org/pubmed/16688755
xref: http://identifiers.org/pubmed/20188572
xref: http://identifiers.org/pubmed/21350678
comment: The retinoid cycle (also referred to as the visual cycle) is the process by which the visual chromophore 11-cis-retinal (11cRAL) is released from light-activated opsins in the form all-trans-retinal and isomerized back to its 11-cis isomer ready for another photoisomerization reaction. This process involves oxidation, reduction and isomerization reactions and take place in the retinal pigment epithelium (RPE) and photoreceptor segments of the eye (von Lintig 2012, Blomhoff & Blomhoff 2006, von Lintig et al. 2010, D'Ambrosio et al. 2011). This section describes the retinoid cycle in rods during dark/twilight conditions.

Active Calmodulin (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry711
component stoichiometry: Stoichiometry712
component: PhysicalEntity71
component: SmallMolecule21
xref: UnificationXref2940
cellular location: GO_0005886
comment: Reactome DB_ID: 5612879

palmitoylated, myristoylated eNOS dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry705
component stoichiometry: Stoichiometry706
component stoichiometry: Stoichiometry707
component stoichiometry: Stoichiometry708
component stoichiometry: Stoichiometry709
component: SmallMolecule45
component: SmallMolecule44
component: SmallMolecule117
component: SmallMolecule109
component: Protein884
xref: UnificationXref2938
cellular location: GO_0005886
comment: Reactome DB_ID: 5612877

UnificationXref3829
type: UnificationXref
id: REACT_15966
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_15966.1

CDC42:GTP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry738
component stoichiometry: Stoichiometry739
component: Protein896
component: SmallMolecule26
xref: UnificationXref2973
cellular location: GO_0005886
comment: Reactome DB_ID: 5617891

UnificationXref3824
type: UnificationXref
id: 5613543
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613543

Cdc42-GDP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry736
component stoichiometry: Stoichiometry737
component: SmallMolecule119
component: Protein896
xref: UnificationXref2972
cellular location: GO_0005886
comment: Reactome DB_ID: 5617890

UnificationXref3823
type: UnificationXref
id: 5613542
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613542

RhoGTPase:GDP (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry746
component stoichiometry: Stoichiometry745
component: Protein913
component: SmallMolecule119
xref: UnificationXref3039
cellular location: GO_0005886
comment: Reactome DB_ID: 5612289

UnificationXref3822
type: UnificationXref
id: P07284
db: UniProt

DAG:active PKC:Ca+2 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry744
component stoichiometry: Stoichiometry742
component stoichiometry: Stoichiometry743
component: SmallMolecule76
component: Protein902
component: SmallMolecule9
xref: UnificationXref2990
cellular location: GO_0005886
comment: Reactome DB_ID: 5617878

UnificationXref3821
type: UnificationXref
id: REACT_17419
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_17419.1

http://identifiers.org/pubmed/9305914
type: PublicationXref
id: 9305914
author: Ishimi, Y
db: Pubmed
title: A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex.
source: J Biol Chem 272:24508-13
year: 1997

p-S1177-eNOS dimer (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry719
component stoichiometry: Stoichiometry724
component stoichiometry: Stoichiometry722
component stoichiometry: Stoichiometry723
component stoichiometry: Stoichiometry720
component stoichiometry: Stoichiometry721
component: SmallMolecule45
component: SmallMolecule44
component: SmallMolecule118
component: SmallMolecule117
component: Protein895
component: SmallMolecule109
xref: UnificationXref2957
cellular location: GO_0005886
comment: Reactome DB_ID: 5612901

UnificationXref3828
type: UnificationXref
id: 379749
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379749

p-S1177-eNOS:CaM:HSP90:p-AKT1 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry718
component stoichiometry: Stoichiometry717
component stoichiometry: Stoichiometry728
component stoichiometry: Stoichiometry725
component: Protein712
component: p-S1177-eNOS dimer (name copied from entity in Homo sapiens)
component: Protein892
component: 4xCa2+:CaM (name copied from entity in Homo sapiens)
xref: UnificationXref2959
cellular location: GO_0005886
comment: Reactome DB_ID: 5612902

UnificationXref3827
type: UnificationXref
id: CHEBI:29180
db: ChEBI

p-S1177-eNOS:CaM:HSP90:p-AKT1:BH4 (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry729
component stoichiometry: Stoichiometry730
component stoichiometry: Stoichiometry731
component stoichiometry: Stoichiometry732
component stoichiometry: Stoichiometry733
component: SmallMolecule118
component: Protein712
component: p-S1177-eNOS dimer (name copied from entity in Homo sapiens)
component: Protein892
component: 4xCa2+:CaM (name copied from entity in Homo sapiens)
xref: UnificationXref2962
cellular location: GO_0005886
comment: Reactome DB_ID: 5612904

UnificationXref3826
type: UnificationXref
id: REACT_208057
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_208057.2

4xCa2+:CaM (name copied from entity in Homo sapiens)
type: Complex
data source: Provenance1
component stoichiometry: Stoichiometry727
component stoichiometry: Stoichiometry726
component: PhysicalEntity7
component: SmallMolecule9
xref: UnificationXref2958
cellular location: GO_0005829
comment: Reactome DB_ID: 5612898

UnificationXref3825
type: UnificationXref
id: 5613545
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613545

Signaling by ERBB2
type: Pathway
data source: Provenance1
pathway component: REACT 191485.3
pathway component: REACT 188923.3
pathway component: REACT 191492.3
pathway component: REACT 188678.3
evidence: Evidence438
xref: UnificationXref3019
xref: UnificationXref3020
pathway order: PathwayStep427
pathway order: PathwayStep429
pathway order: PathwayStep428
pathway order: PathwayStep430
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

Evidence478
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/7739543
xref: http://identifiers.org/pubmed/8065359
xref: http://identifiers.org/pubmed/23140633
xref: http://identifiers.org/pubmed/23256519
xref: http://identifiers.org/pubmed/21903638
xref: http://identifiers.org/pubmed/22935904
comment: Humans and mice have 19 identified WNT proteins that were originally classified as either 'canonical' or 'non-canonical' depending upon whether they were able to transform the mouse mammary epithelial cell line C57MG and to induce secondary axis formation in Xenopus (Wong et al, 1994; Du et al, 1995). So-called canonical WNTs, including Wnt1, 3, 3a and 7, initiate signaling pathways that destabilize the destruction complex and allow beta-catenin to accumulate and translocate to the nucleus where it promotes transcription (reviewed in Saito-Diaz et al, 2013). Non-canonical WNTs, including Wnt 2, 4, 5a, 5b, 6, 7b, and Wnt11 activate beta-catenin-independent responses that regulate many aspects of morphogenesis and development, often by impinging on the cytoskeleton (reviewed in van Amerongen, 2012). Two of the main beta-catenin-independent pathways are the Planar Cell Polarity (PCP) pathway, which controls the establishment of polarity in the plane of a field of cells, and the WNT/Ca2+ pathway, which promotes the release of intracellular calcium and regulates numerous downstream effectors (reviewed in Gao, 2012; De, 2011).

Evidence479
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/23256519
xref: http://identifiers.org/pubmed/17143292
xref: http://identifiers.org/pubmed/19204114
xref: http://identifiers.org/pubmed/10858654
xref: http://identifiers.org/pubmed/17230199
xref: http://identifiers.org/pubmed/18710302
xref: http://identifiers.org/pubmed/19619488
xref: http://identifiers.org/pubmed/19530173
xref: http://identifiers.org/pubmed/20576942
xref: http://identifiers.org/pubmed/12967557
xref: http://identifiers.org/pubmed/19365405
xref: http://identifiers.org/pubmed/16099039
xref: http://identifiers.org/pubmed/22952392
comment: WNT signaling pathways control a wide range of developmental and adult process in metozoans including cell proliferation, cell fate decisions, cell polarity and stem cell maintenance (reviewed in Saito-Diaz et al, 2013; MacDonald et al, 2009). The pathway is named for the WNT ligands, a large family of secreted cysteine-rich glycoproteins. At least 19 WNT members have been identified in humans and mice with distinct expression patterns during development (reviewed in Willert and Nusse, 2012). These ligands can activate at least three different downstream signaling cascades depending on which receptors they engage. In the so-called 'canonical' WNT signaling pathway, WNT ligands bind one of the 10 human Frizzled (FZD) receptors in conjunction with the LRP5/6 co-receptors to activate a transcriptional cascade that controls processes such as cell fate, proliferation and self-renenwal of stem cells. Engagement of the FZD-LRP receptor by WNT ligand results in the stabilization and translocation of cytosolic beta-catenin to the nucleus where it is a co-activator for LEF (lymphoid enhancer-binding factor)- and TCF (T cell factor) -dependent transcription. In the absence of WNT ligand, cytosolic beta-catenin is phosphorylated by a degradation complex consisting of glycogen synthase kinase 3 (GSK3), casein kinase 1 (CK1), Axin and Adenomatous polyposis coli (APC), and subsequently ubiquitinated and degraded by the 26S proteasome (reviewed in Saito-Diaz et al, 2013; Kimmelman and Xu, 2006). In addition to the beta-catenin-dependent transcriptional response, WNT signaling can also activate distinct non-transcriptional pathways that regulate cell migration and polarity. These beta-catenin-independent 'non-canonical' pathways signal through Frizzled receptors independently of LRP5/6, or occur through the tyrosine kinase receptors ROR and RYK (reviewed in Veeman et al, 2003; James et al, 2009). Non-canonical WNT pathways are best studied in Drosophila where the planar cell polarit…

UnificationXref3820
type: UnificationXref
id: 379738
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379738

Evidence476
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/21118996
comment: Dimerization and autophosphorylation at T298 is required for NLK nuclear localization (Ishitani et al, 2011).

http://identifiers.org/pubmed/14638695
type: PublicationXref
id: 14638695
author: Lu, M
author: Haney, LB
author: Brugnera, E
author: Hengartner, MO
author: Tosello-Trampont, AC
author: Klingele, D
author: Ravichandran, KS
author: Kinchen, JM
author: Chen, Q
author: Grimsley, CM
db: Pubmed
title: Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration
source: J Biol Chem 279:6087-97
year: 2004

Evidence477
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/21181886
xref: http://identifiers.org/pubmed/21903638
xref: http://identifiers.org/pubmed/16099039
comment: A number of so called non-canonical WNT ligands have been shown to promote intracellular calcium release upon FZD binding. This beta-catenin-independent WNT pathway acts through heterotrimeric G proteins and promotes calcium release through phophoinositol signaling and activation of phosphodiesterase (PDE). Downstream effectors include the calcium/calmodulin-dependent kinase II (CaMK2) and PKC (reviewed in De, 2011). The WNT Ca2+ pathway is important in dorsoventral polarity, convergent extension and organ formation in vertebrates and also has roles in negatively regulating 'canonical' beta-catenin-dependent transcription. Non-canonical WNT Ca2+ signaling is also implicated in inflammatory response and cancer (reviewed in Kohn and Moon, 2005; Sugimura and Li, 2010).

Evidence474
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/21554866
xref: http://identifiers.org/pubmed/23256519
xref: http://identifiers.org/pubmed/22653731
xref: http://identifiers.org/pubmed/19837038
xref: http://identifiers.org/pubmed/22983114
xref: http://identifiers.org/pubmed/21725318
xref: http://identifiers.org/pubmed/16678096
xref: http://identifiers.org/pubmed/22952392
xref: http://identifiers.org/pubmed/17108000
xref: http://identifiers.org/pubmed/16678095
xref: http://identifiers.org/pubmed/23260141
xref: http://identifiers.org/pubmed/21768372
xref: http://identifiers.org/pubmed/22796206
xref: http://identifiers.org/pubmed/17141155
comment: 19 WNT proteins have been identified in human cells. The WNTs are members of a conserved metazoan family of secreted morphogens that activate several signaling pathways in the responding cell: the canonical (beta-catenin) WNT signaling cascade and several non-canonical pathways, including the planar cell polarity (PCP), the regulation of intracellular calcium signaling and activation of JNK kinases. WNT proteins exist in a gradient outside the secreting cell and are able to act over both short and long ranges to promote proliferation, changes in cell migration and polarity and tissue homeostasis, among others (reviewed in Saito-Diaz et al, 2012; Willert and Nusse, 2012). The WNTs are ~40kDa proteins with 23 conserved cysteine residues in the N-terminal that may form intramolecular disulphide bonds. They also contain an N-terminal signal sequence and a number of N-linked glycosylation sites (Janda et al, 2012). In addition to being glycosylated, WNTs are also lipid-modified in the endoplasmic reticulum by a WNT-specific O-acyl-transferase, Porcupine (PORCN), contributing to their characteristic hydrophobicity. PORCN-dependent palmitoylation is required for the secretion of WNT as well as its signaling activity, as either depletion of PORCN or mutation of the conserved serine acylation site results in the intracellular accumulation of WNT ligand (Takada et al, 2006; Barrott et al, 2011; Biechele et al, 2011; reviewed in Willert and Nusse, 2012). Secretion of WNT requires a number of other dedicated factors including the sorting receptor Wntless (WLS) (also knownas Evi, Sprinter, and GPR177), which binds WNT and escorts it to the cell surface (Banziger et al, 2006; Bartscherer et al, 2006; Goodman et al, 2006). A WNT-specific retromer containing SNX3 is subsequently required for the recycling of WLS back to the Golgi (reviewed in Herr et al, 2012; Johannes and Wunder, 2011). Once at the cell surface, WNT makes extensive contacts with components of the extracellular mat…

Evidence475
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10858654
xref: http://identifiers.org/pubmed/10395542
xref: http://identifiers.org/pubmed/12086864
xref: http://identifiers.org/pubmed/17426020
xref: http://identifiers.org/pubmed/19177143
comment: Ectopic expression of Xwnt5a or Rfz2 in Xenopus embryos results in PKC translocation to the plasma membrane in a G-protein-dependent manner (Sheldahl et al, 1999; reviewed in Kuhl et al, 2000). PKC activation in response to WNT5A has also been demonstrated in human metastatic melanoma cell lines, contributing to cytoskeletal reorganization leading to invasiveness and motility as well as promoting the epithelial to mesenchymal transition (Weeraratna et al, 2002; Dissanyake et al, 2007; O'Connell et al, 2009)

Evidence472
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16902930
xref: http://identifiers.org/pubmed/10202136
xref: http://identifiers.org/pubmed/18043707
comment: G protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors in humans, accounting for more than 1% of the protein-coding capacity of the human genome. All known GPCRs share a common architecture of seven membrane-spanning helices connected by intra- and extracellular loops. The extracellular loops contain two highly-conserved cysteine residues that form disulphide bonds to stabilize the structure of the receptor. They recognize diverse messengers such as light, odorants, small molecules, hormones and neurotransmitters. Most GPCRs act as guanine nucleotide exchange factors; activated by ligand binding, they promote GDP-GTP exchange on associated heterotrimeric guanine nucleotide-binding (G) proteins. There are two models for GPCR-G Protein interactions: 1) ligand-GPCR binding first, then binding to G Proteins; 2) "Pre-coupling" of GPCRs and G Proteins before ligand binding (review Oldham WM and Hamm HE, 2008). These in turn activate effector enzymes or ion channels. GPCRs are involved in a range of physiological roles which include the visual sense, smell, behavioural regulation, functions of the autonomic nervous system and regulation of the immune system and inflammation. GPCRs are divided into 6 classes based on sequence homology and functional similarity; the main mammalian families are classes A/1-C/3; Class A/1 (Rhodopsin-like) Class B/2 (Secretin receptor family) Class C/3 (Metabotropic glutamate/pheromones) Class D/4 (fungal mating pheromone receptors) Class E/5 (cAMP receptors) Class F/6 (Frizzled/Smoothened) Here, those Class A/1 (Rhodopsin-like) receptors that bind peptide ligands have been annotated. The binding events mediated by other classes of receptors, as well as the downstream events triggered by receptor-ligand interactions will be annotated in future releases of Reactome.

Evidence473
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/21725318
xref: http://identifiers.org/pubmed/22952392
comment: Retromer is believed to escort WLS from the early endosome back to the Golgi for subsequent rounds of WNT secretion (reviewed in Johannes and Wunder, 2011; Willert and Nusse, 2012 ).

Evidence470
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/20398727
xref: http://identifiers.org/pubmed/16816139
comment: Gastrin, through the action of diacylglycerol produced from downstream G alpha (q) events, transactivates EGFR via a PKC-mediated pathway by activation of MMP3 (Matrix Metalloproteinase 3) which allows formation of mature HBEGF (heparin-binding epidermal growth factor) by cleaving pro-HBEGF. Mature HBEGF is then free to bind the EGFR, resulting in EGFR activation (Dufresne et al. 2006, Liebmann 2011).

Evidence471
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17698287
xref: http://identifiers.org/pubmed/7491953
xref: http://identifiers.org/pubmed/10413847
comment: Gastrin is a hormone whose main function is to stimulate secretion of hydrochloric acid by the gastric mucosa, which results in gastrin formation inhibition. This hormone also acts as a mitogenic factor for gastrointestinal epithelial cells. Gastrin has two biologically active peptide forms, G34 and G17.Gastrin gene expression is upregulated in both a number of pre-malignant conditions and in established cancer through a variety of mechanisms. Depending on the tissue where it is expressed and the level of expression, differential processing of the polypeptide product leads to the production of different biologically active peptides. In turn, acting through the classical gastrin cholecystokinin B receptor CCK-BR, its isoforms and alternative receptors, these peptides trigger signalling pathways which influence the expression of downstream genes that affect cell survival, angiogenesis and invasion (Wank 1995, de Weerth et al. 1999, Grabowska & Watson 2007)

http://identifiers.org/pubmed/8114698
type: PublicationXref
id: 8114698
author: Nevins, JR
author: Ohtani, K
db: Pubmed
title: Functional properties of a Drosophila homolog of the E2F1 gene
source: Mol Cell Biol 14:1603-12
year: 1994

UnificationXref3833
type: UnificationXref
id: P04801
db: UniProt

UnificationXref3832
type: UnificationXref
id: REACT_17415
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_17415.1

UnificationXref3835
type: UnificationXref
id: 5613556
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613556

UnificationXref3834
type: UnificationXref
id: 5613555
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613555

UnificationXref3837
type: UnificationXref
id: REACT_209330
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_209330.2

UnificationXref3836
type: UnificationXref
id: 5613558
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613558

UnificationXref3839
type: UnificationXref
id: 379763
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379763

UnificationXref3838
type: UnificationXref
id: CHEBI:29181
db: ChEBI

Evidence469
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11588141
comment: Diacylglycerol, produced by PLC beta-mediated PIP2 hydrolysis in G alpha (q) signalling, remains in the plasma membrane and binds Protein Kinase C alpha (PKC-alpha), causing PKC-alpha to translocate from the cytosol to the plasma membrane. PKC-alpha is thereby activated and phosphorylates target proteins.

Evidence465
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16183910
xref: http://identifiers.org/pubmed/9218123
xref: http://identifiers.org/pubmed/1335363
comment: The phospholipase C (PLC) family of enzymes is both diverse and complex. The isoforms beta, gamma and delta (each have subtypes) make up the members of this family. PLC hydrolyzes phosphatidylinositol bisphosphate (PIP2) into two second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 mobilizes intracellular calcium stores while DAG activates protein kinase C isoforms which are involved in regulatory functions.

Evidence466
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9218123
xref: http://identifiers.org/pubmed/9422713
comment: When dissociated Galpha-GTP and Gbeta-gamma can activate or inhibit different signalling cascades and effector proteins. The precise pathways depends on the identity of the alpha and beta/gamma subtypes.

Evidence467
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/14744247
xref: http://identifiers.org/pubmed/2908293
comment: Dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32), was identified as a major target for dopamine and protein kinase A (PKA) in striatum. Recent advances now indicate that regulation DARPP-32 phosphorylation provides a mechanism for integrating information arriving at dopaminoceptive neurons, in multiple brain regions, via a variety of neurotransmitters, neuromodulators, neuropeptides, and steroid hormones. Activation of PKA or PKG stimulates DARPP-32 phosphorylation at Thr34, converting DARPP-32 into a potent inhibitor of protein phosphatase-1 (PP-1). DARPP-32 is also phosphorylated at Thr75 by Cdk5, converting DARPP-32 into an inhibitor of PKA. Thus, DARPP-32 has the unique property of being a dual-function protein, acting either as an inhibitor of PP-1 or of PKA.

UnificationXref3830
type: UnificationXref
id: CHEBI:29163
db: ChEBI

Evidence468
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9218123
xref: http://identifiers.org/pubmed/16612131
xref: http://identifiers.org/pubmed/9422713
comment: Opioids are chemical substances similar to opiates, the active substances found in opium (morphine, codeine etc.). Opioid action is mediated by the receptors for endogenous opioids; peptides such as the enkephalins, the endorphins or the dynorphins. Opioids possess powerful analgesic and sedative effects, and are widely used as pain-killers. Their main side-effect is the rapid establishment of a strong addiction. Opioids receptors are G-protein coupled receptors (GPCR). There are four classes of receptors: mu (MOR), kappa (KOR) and delta (DOR), and the nociceptin receptor (NOP).

UnificationXref3831
type: UnificationXref
id: 379783
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=379783

Evidence461
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15705797
xref: http://identifiers.org/pubmed/16182515
xref: http://identifiers.org/pubmed/11753430
comment: The active form of G protein alpha subunit q (Gq-alpha) was found to activate phospholipase C beta-1 (PLC-beta1), in investigations using bovine membranes. Subsequently, all 4 human isoforms have been shown to be activated by Gq, though activation of PLCbeta-4 is limited. In recombinant assays, several activated rat G alpha q family members were found to stimulate human PLC-beta isoforms with the same rank order of decreasing potency. PLC-beta1 stimulation was slightly more than for PLC-beta3; PLC-beta3 stimulation was 10-fold greater than for beta-2. PLC-beta2 is expressed specifically in hematopoietic cells. PLC-beta acts directly on Gq to accelerate hydrolysis of bound GTP, thus PLC-betas are GTPase activating proteins (GAPs). The crystal structure of the C-terminal region from Turkey PLC-beta, revealed a novel fold composed almost entirely of three long helices forming a coiled-coil that dimerizes along its long axis in an antiparallel orientation. The extent of the dimer interface and gel exclusion chromatography data suggest that PLC-betas are functionally dimeric.

Evidence462
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11118617
comment: The phospholipase C (PLC) family of enzymes is both diverse and complex. The isoforms beta, gamma and delta (each have subtypes) make up the members of this family. One type, PLC-beta1, hydrolyzes phosphatidylinositol bisphosphate (PIP2) into two second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 mobilizes intracellular calcium stores while DAG activates protein kinase C isoforms which are involved in regulatory functions.

Evidence463
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/1322796
comment: PLC-beta1 is a GTPase-activating protein (GAP) for Gq-alpha, exchanging GTP for GDP and releasing the alpha subunit to cycle back to the membrane and reassociate with the beta-gamma subunits. Between itself and the receptor, they regulate the amplitude of the PLC signal and the rates of signal initiation and termination.

Evidence464
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11162741
xref: http://identifiers.org/pubmed/18083096
xref: http://identifiers.org/pubmed/16076488
xref: http://identifiers.org/pubmed/17697045
comment: Calcium, as the ion Ca2+, is essential in many biological processes. The majority of Ca2+ in many organisms is bound to phosphates which form skeletal structures and also buffer Ca2+ levels in extracellular fluids (typically 1 millimolar). Intracellular free Ca2+, by contrast, is 10,000 times lower than the outside of the cell (typically 10 micromolar). This concentration gradient is used to import Ca2+ into cells where it acts as a second messenger.

Evidence460
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15294442
xref: http://identifiers.org/pubmed/9218123
xref: http://identifiers.org/pubmed/12184727
comment: Receptor activated heterotrimeric G proteins consist of the Galpha and the tightly associated Gbeta-gamma subunits. When a ligand binds to a G protein-coupled receptor, it stabilises a conformation with an high affinity for the G-protein bound to GDP. GDP is then exchanged for GTP on the Galpha subunit. This exchange triggers the dissociation of the Galpha subunit from the Gbeta-gamma dimer and the receptor. Galpha-GTP and Gbeta-gamma, can then modulate different signalling cascades and effector proteins, while the receptor is able to activate another G protein, resulting in an amplification cascade. The Galpha subunit will eventually hydrolyze the attached GTP to GDP by its inherent enzymatic activity, allowing it to reassociate with Gbeta-gamma and start a new cycle.

Stoichiometry1604
type: Stoichiometry
physical entity: Protein1642
stoichiometric coefficient: 4.0

Stoichiometry1605
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 4.0

Stoichiometry1602
type: Stoichiometry
physical entity: Protein1641
stoichiometric coefficient: 4.0

Stoichiometry1603
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 4.0

Stoichiometry1608
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

Stoichiometry1609
type: Stoichiometry
physical entity: Protein1643
stoichiometric coefficient: 1.0

Stoichiometry1606
type: Stoichiometry
physical entity: SmallMolecule12
stoichiometric coefficient: 2.0

Stoichiometry1607
type: Stoichiometry
physical entity: SmallMolecule13
stoichiometric coefficient: 2.0

http://identifiers.org/pubmed/20188670
type: PublicationXref
id: 20188670
author: Riemer, J
author: Wagener, N
author: Chwalla, I
author: Herrmann, JM
author: Longen, S
author: Bien, M
db: Pubmed
title: Mitochondrial disulfide bond formation is driven by intersubunit electron transfer in Erv1 and proofread by glutathione
source: Mol Cell 37:516-28
year: 2010

SequenceSite211
type: SequenceSite
position status: EQUAL
sequence position: 76

SequenceSite212
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite210
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite215
type: SequenceSite
position status: EQUAL
sequence position: 76

SequenceSite216
type: SequenceSite
position status: EQUAL
sequence position: 77

SequenceSite213
type: SequenceSite
position status: EQUAL
sequence position: 76

SequenceSite214
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite219
type: SequenceSite
position status: EQUAL
sequence position: 228

Stoichiometry1601
type: Stoichiometry
physical entity: Protein1639
stoichiometric coefficient: 2.0

Stoichiometry1600
type: Stoichiometry
physical entity: SmallMolecule314
stoichiometric coefficient: 2.0

SequenceSite217
type: SequenceSite
position status: EQUAL
sequence position: 152

SequenceSite218
type: SequenceSite
position status: EQUAL
sequence position: 153

Stoichiometry1613
type: Stoichiometry
physical entity: Protein1650
stoichiometric coefficient: 2.0

Stoichiometry1614
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

http://identifiers.org/pubmed/20042001
type: PublicationXref
id: 20042001
author: Wolf, George
db: Pubmed
title: Retinoic acid activation of peroxisome proliferation-activated receptor delta represses obesity and insulin resistance
source: Nutr. Rev. 68:67-70
year: 2010

Stoichiometry1615
type: Stoichiometry
physical entity: Protein1653
stoichiometric coefficient: 2.0

Stoichiometry1616
type: Stoichiometry
physical entity: SmallMolecule274
stoichiometric coefficient: 8.0

UniProt:Q12403
type: ProteinReference
name: ERP3
xref: UnificationXref2442
organism: http://identifiers.org/taxonomy/4932

Stoichiometry1617
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

UniProt:Q12404
type: ProteinReference
name: MPD1
xref: UnificationXref5302
organism: http://identifiers.org/taxonomy/4932

Stoichiometry1618
type: Stoichiometry
physical entity: Protein1656
stoichiometric coefficient: 2.0

Stoichiometry1619
type: Stoichiometry
physical entity: Protein1653
stoichiometric coefficient: 2.0

Degradation of GABA
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction413
pathway component: BiochemicalReaction414
evidence: Evidence799
xref: UnificationXref5392
xref: UnificationXref5393
pathway order: PathwayStep784
pathway order: PathwayStep785
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

SequenceSite200
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite201
type: SequenceSite
position status: EQUAL
sequence position: 313

SequenceSite202
type: SequenceSite
position status: EQUAL
sequence position: 213

SequenceSite203
type: SequenceSite
position status: EQUAL
sequence position: 524

SequenceSite204
type: SequenceSite
position status: EQUAL
sequence position: 213

UniProt:P24583
type: ProteinReference
name: PKC1
xref: UnificationXref98
organism: http://identifiers.org/taxonomy/4932

SequenceSite205
type: SequenceSite
position status: EQUAL
sequence position: 524

SequenceSite206
type: SequenceSite
position status: EQUAL
sequence position: 213

Stoichiometry1610
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

SequenceSite207
type: SequenceSite
position status: EQUAL
sequence position: 524

SequenceSite208
type: SequenceSite
position status: EQUAL
sequence position: 1

Stoichiometry1612
type: Stoichiometry
physical entity: Protein1647
stoichiometric coefficient: 8.0

SequenceSite209
type: SequenceSite
position status: EQUAL
sequence position: 76

Stoichiometry1611
type: Stoichiometry
physical entity: Protein1646
stoichiometric coefficient: 1.0

UnificationXref8499
type: UnificationXref
id: CHEBI:17351
db: ChEBI

UnificationXref8498
type: UnificationXref
id: REACT_188947
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_188947.3

UnificationXref8497
type: UnificationXref
id: 5618632
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618632

UnificationXref8496
type: UnificationXref
id: REACT_187464
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_187464.3

UnificationXref8495
type: UnificationXref
id: 5616796
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616796

UnificationXref8494
type: UnificationXref
id: REACT_123067
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_123067.1

UnificationXref8493
type: UnificationXref
id: 2066763
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2066763

UnificationXref8492
type: UnificationXref
id: CHEBI:28125
db: ChEBI

UnificationXref8491
type: UnificationXref
id: REACT_187468
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_187468.3

UnificationXref9989
type: UnificationXref
id: 5608466
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608466

http://identifiers.org/pubmed/15581364
type: PublicationXref
id: 15581364
author: Zhai, H
author: McLafferty, FW
author: Brand, LA
author: Begley, TP
author: Strauss, E
db: Pubmed
title: Mechanistic studies on phosphopantothenoylcysteine decarboxylase: trapping of an enethiolate intermediate with a mechanism-based inactivating agent
source: Biochemistry 43:15520-33
year: 2004

UnificationXref9988
type: UnificationXref
id: P00812
db: UniProt

UnificationXref9985
type: UnificationXref
id: REACT_2669
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2669.1

http://identifiers.org/pubmed/17851529
type: PublicationXref
id: 17851529
author: Issaeva, Irina
author: Chen, Shuzhen
author: Shi, Yang
author: Roberts, Thomas M
author: Rinn, John L
author: Canaani, Eli
author: Iwase, Shigeki
author: Bayliss, Peter E
author: Lan, Fei
author: Wang, Jordon K
author: Alpatov, Roman
author: Chang, HY
author: Whetstine, Johnathan R
db: Pubmed
title: A histone H3 lysine 27 demethylase regulates animal posterior development
source: Nature 449:689-94
year: 2007

UnificationXref9984
type: UnificationXref
id: 29514
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29514

http://identifiers.org/pubmed/26687
type: PublicationXref
id: 26687
author: Hayaishi, Osamu
author: Shimizu, T
author: Nomiyama, S
author: Hirata, F
db: Pubmed
title: Indoleamine 2,3-dioxygenase. Purification and some properties
source: J Biol Chem 253:4700-4706
year: 1978

UnificationXref9987
type: UnificationXref
id: REACT_5017
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5017.2

UnificationXref9986
type: UnificationXref
id: 29498
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29498

UnificationXref9981
type: UnificationXref
id: 5608476
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608476

UnificationXref9980
type: UnificationXref
id: 5608474
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608474

UnificationXref9983
type: UnificationXref
id: CHEBI:16199
db: ChEBI

UnificationXref9982
type: UnificationXref
id: REACT_246623
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_246623.1

ROM2
type: ProteinReference
name: UniProt:P51862
xref: UnificationXref3053
organism: http://identifiers.org/taxonomy/4932

Astrocytic Glutamate-Glutamine Uptake And Metabolism
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction416
evidence: Evidence807
xref: UnificationXref5424
xref: UnificationXref5423
pathway order: PathwayStep793
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

http://identifiers.org/pubmed/10522552
type: PublicationXref
id: 10522552
author: Ponka, P
db: Pubmed
title: Cell biology of heme
source: Am J Med Sci 318:241-56
year: 1999

UnificationXref9999
type: UnificationXref
id: Q12375
db: UniProt

UnificationXref9998
type: UnificationXref
id: REACT_225766
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_225766.2

UnificationXref9997
type: UnificationXref
id: 5614872
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5614872

UnificationXref9996
type: UnificationXref
id: 5614870
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5614870

UnificationXref9995
type: UnificationXref
id: 5614869
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5614869

UnificationXref9994
type: UnificationXref
id: REACT_21729
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_21729.1

UnificationXref9993
type: UnificationXref
id: 374061
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=374061

UnificationXref9992
type: UnificationXref
id: REACT_234723
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_234723.1

http://identifiers.org/pubmed/16116451
type: PublicationXref
id: 16116451
author: Szabó, SI
author: Makara, JK
author: Fegley, D
author: Freund, TF
author: Tontini, A
author: Duranti, A
author: Mor, M
author: Astarita, G
author: Piomelli, D
author: Rivara, S
author: Tarzia, G
author: Kathuria, S
db: Pubmed
title: Selective inhibition of 2-AG hydrolysis enhances endocannabinoid signaling in hippocampus
source: Nat Neurosci 8:1139-41
year: 2005

UnificationXref9991
type: UnificationXref
id: 5608469
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608469

UnificationXref9990
type: UnificationXref
id: 5608467
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608467

UnificationXref11210
type: UnificationXref
id: REACT_216253
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_216253.2

UnificationXref8471
type: UnificationXref
id: REACT_187461
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_187461.3

UnificationXref8472
type: UnificationXref
id: CHEBI:65139
db: ChEBI

UnificationXref11212
type: UnificationXref
id: REACT_10868
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_10868.2

UnificationXref11211
type: UnificationXref
id: 167012
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=167012

UnificationXref8470
type: UnificationXref
id: 5616787
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616787

UnificationXref8475
type: UnificationXref
id: 5616798
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616798

http://identifiers.org/pubmed/12949583
type: PublicationXref
id: 12949583
author: van den Bosch, M
author: Lowndes, NF
author: Bree, RT
db: Pubmed
title: The MRN complex: coordinating and mediating the response to broken chromosomes.
source: EMBO Rep 4:844-9
year: 2003

UnificationXref8476
type: UnificationXref
id: REACT_263117
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_263117.1

UnificationXref8473
type: UnificationXref
id: 2066767
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2066767

UnificationXref8474
type: UnificationXref
id: REACT_123653
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_123653.1

UnificationXref11218
type: UnificationXref
id: 5615449
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615449

UnificationXref8479
type: UnificationXref
id: REACT_121859
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_121859.1

Stoichiometry1649
type: Stoichiometry
physical entity: SmallMolecule278
stoichiometric coefficient: 8.0

ZRC1
type: ProteinReference
name: UniProt:P20107
xref: UnificationXref10979
organism: http://identifiers.org/taxonomy/4932

UnificationXref11217
type: UnificationXref
id: 5615447
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615447

Stoichiometry1648
type: Stoichiometry
physical entity: Protein1653
stoichiometric coefficient: 2.0

UnificationXref8477
type: UnificationXref
id: CHEBI:65130
db: ChEBI

Stoichiometry1647
type: Stoichiometry
physical entity: Protein1674
stoichiometric coefficient: 2.0

UnificationXref11219
type: UnificationXref
id: REACT_182148
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_182148.3

UnificationXref8478
type: UnificationXref
id: 2066766
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2066766

Stoichiometry1646
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

UnificationXref11214
type: UnificationXref
id: 5615444
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615444

UnificationXref11213
type: UnificationXref
id: P13586
db: UniProt

UnificationXref11216
type: UnificationXref
id: 5615446
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615446

UnificationXref11215
type: UnificationXref
id: 5615445
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615445

Stoichiometry1640
type: Stoichiometry
physical entity: SmallMolecule274
stoichiometric coefficient: 8.0

Stoichiometry1641
type: Stoichiometry
physical entity: Protein1668
stoichiometric coefficient: 2.0

Stoichiometry1644
type: Stoichiometry
physical entity: SmallMolecule278
stoichiometric coefficient: 8.0

Stoichiometry1645
type: Stoichiometry
physical entity: SmallMolecule274
stoichiometric coefficient: 8.0

UnificationXref9960
type: UnificationXref
id: 5608454
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608454

Stoichiometry1642
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

UnificationXref9961
type: UnificationXref
id: REACT_189977
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_189977.3

Stoichiometry1643
type: Stoichiometry
physical entity: Protein1671
stoichiometric coefficient: 2.0

UnificationXref9962
type: UnificationXref
id: 5608455
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608455

UnificationXref9963
type: UnificationXref
id: 113567
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113567

UnificationXref9964
type: UnificationXref
id: REACT_2266
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2266.2

UnificationXref9965
type: UnificationXref
id: P05150
db: UniProt

UnificationXref9966
type: UnificationXref
id: 5608459
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608459

UnificationXref9967
type: UnificationXref
id: 5608460
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608460

UnificationXref9968
type: UnificationXref
id: 5608462
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608462

UnificationXref9969
type: UnificationXref
id: REACT_235076
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_235076.1

UnificationXref11223
type: UnificationXref
id: 939747
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939747

UnificationXref8480
type: UnificationXref
id: 5616795
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616795

UnificationXref11222
type: UnificationXref
id: REACT_25558
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_25558.2

UnificationXref8481
type: UnificationXref
id: REACT_187463
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_187463.3

UnificationXref11221
type: UnificationXref
id: 947595
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=947595

UnificationXref8482
type: UnificationXref
id: CHEBI:65131
db: ChEBI

UnificationXref11220
type: UnificationXref
id: GO:0009897
db: GENE ONTOLOGY

UnificationXref8483
type: UnificationXref
id: 2066762
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2066762

UnificationXref8484
type: UnificationXref
id: REACT_124098
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_124098.1

http://identifiers.org/pubmed/2995393
type: PublicationXref
id: 2995393
author: Fitzpatrick, F
author: McGee, J
db: Pubmed
title: Enzymatic hydration of leukotriene A4. Purification and characterization of a novel epoxide hydrolase from human erythrocytes
source: J Biol Chem 260:12832-7
year: 1985

UnificationXref8485
type: UnificationXref
id: 5616797
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616797

UnificationXref8486
type: UnificationXref
id: REACT_187460
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_187460.3

UnificationXref8487
type: UnificationXref
id: CHEBI:65132
db: ChEBI

UnificationXref8488
type: UnificationXref
id: 2066765
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2066765

Stoichiometry1658
type: Stoichiometry
physical entity: Protein1665
stoichiometric coefficient: 2.0

UnificationXref8489
type: UnificationXref
id: REACT_124023
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_124023.1

Stoichiometry1657
type: Stoichiometry
physical entity: Protein1677
stoichiometric coefficient: 2.0

UnificationXref11229
type: UnificationXref
id: 947592
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=947592

UnificationXref11228
type: UnificationXref
id: REACT_26149
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_26149.2

Stoichiometry1659
type: Stoichiometry
physical entity: SmallMolecule278
stoichiometric coefficient: 8.0

UnificationXref11227
type: UnificationXref
id: 939760
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=939760

UnificationXref11226
type: UnificationXref
id: GO:0009898
db: GENE ONTOLOGY

UnificationXref11225
type: UnificationXref
id: 5615456
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615456

UnificationXref11224
type: UnificationXref
id: REACT_26138
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_26138.2

Stoichiometry1650
type: Stoichiometry
physical entity: SmallMolecule274
stoichiometric coefficient: 8.0

Stoichiometry1651
type: Stoichiometry
physical entity: Protein1659
stoichiometric coefficient: 2.0

Stoichiometry1652
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

UnificationXref9971
type: UnificationXref
id: 34575
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=34575

Stoichiometry1653
type: Stoichiometry
physical entity: Protein1674
stoichiometric coefficient: 2.0

UnificationXref9972
type: UnificationXref
id: REACT_5577
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5577.1

Stoichiometry1654
type: Stoichiometry
physical entity: SmallMolecule278
stoichiometric coefficient: 8.0

Stoichiometry1655
type: Stoichiometry
physical entity: SmallMolecule274
stoichiometric coefficient: 8.0

UnificationXref9970
type: UnificationXref
id: CHEBI:15682
db: ChEBI

Stoichiometry1656
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

UnificationXref9975
type: UnificationXref
id: 5608481
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608481

UnificationXref9976
type: UnificationXref
id: 5608483
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608483

UnificationXref9973
type: UnificationXref
id: P22768
db: UniProt

UnificationXref9974
type: UnificationXref
id: 5608480
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608480

UnificationXref9979
type: UnificationXref
id: 5608473
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608473

UnificationXref9977
type: UnificationXref
id: REACT_255917
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_255917.1

UnificationXref8490
type: UnificationXref
id: 5616800
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616800

CHEBI:60640 [ChEBI:60640]
type: SmallMoleculeReference
name: CHEBI:60640
xref: UnificationXref4948

UnificationXref9978
type: UnificationXref
id: P04076
db: UniProt

Cleavage of 5-hydroxyluracil by UNG2 glycosylase
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1758
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11415
xref: UnificationXref11414
left: Complex891
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex897
right: SmallMolecule1165

UnificationXref8453
type: UnificationXref
id: REACT_123220
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_123220.1

Cleavage of thymine glycol by hNTH1 glycosylase
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1759
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11420
xref: UnificationXref11419
left: Complex896
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex898
right: PhysicalEntity157

UnificationXref8454
type: UnificationXref
id: CHEBI:63541
db: ChEBI

UnificationXref8451
type: UnificationXref
id: CHEBI:63539
db: ChEBI

UnificationXref8452
type: UnificationXref
id: 2046059
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2046059

UnificationXref9949
type: UnificationXref
id: 5608445
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608445

UnificationXref9948
type: UnificationXref
id: 5608443
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608443

UnificationXref8450
type: UnificationXref
id: REACT_260095
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_260095.1

Elongation by REV1 protein
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1773
conversion direction: LEFT_TO_RIGHT
EC number: 2.7.7.7
xref: UnificationXref11465
xref: UnificationXref11464
left: Complex901
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Note: the coordinates are copied over from Homo sapiens.
right: PhysicalEntity161

Binding of Pol eta to lesioned DNA template
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1775
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11471
xref: UnificationXref11472
left: PhysicalEntity159
left: Note: the coordinates are copied over from Homo sapiens.
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex902

Binding of REV1 to lesioned DNA template
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1771
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11456
xref: UnificationXref11455
left: Note: the coordinates are copied over from Homo sapiens.
left: PhysicalEntity159
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex900

UnificationXref8459
type: UnificationXref
id: REACT_250916
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_250916.1

Stoichiometry1629
type: Stoichiometry
physical entity: Protein1662
stoichiometric coefficient: 2.0

Misinsertion of bases opposite to the lesion by HREV1
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1772
conversion direction: LEFT_TO_RIGHT
EC number: 2.7.7.7
xref: UnificationXref11461
xref: UnificationXref11460
left: Complex900
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex901

Stoichiometry1628
type: Stoichiometry
physical entity: SmallMolecule278
stoichiometric coefficient: 8.0

Cleavage of formamidopyrimidine by hNTH1 glycosylase
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1762
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11429
xref: UnificationXref11430
left: Complex895
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex898
right: SmallMolecule1163

UnificationXref8457
type: UnificationXref
id: 5616780
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616780

Stoichiometry1627
type: Stoichiometry
physical entity: Protein1656
stoichiometric coefficient: 2.0

Interaction between FEN1 and PCNA
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1766
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11441
xref: UnificationXref11440
left: Note: the coordinates are copied over from Homo sapiens.
left: Protein596
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex899

UnificationXref8458
type: UnificationXref
id: 5616794
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616794

Stoichiometry1626
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

Cleavage of cytosine glycol by hNTH1 glycosylase
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1760
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11424
xref: UnificationXref11423
left: Complex893
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: PhysicalEntity158
right: Complex898

UnificationXref8455
type: UnificationXref
id: 2046057
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2046057

Stoichiometry1625
type: Stoichiometry
physical entity: Protein1659
stoichiometric coefficient: 2.0

Cleavage of dihydrouracil by hNTH1 glycosylase
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1761
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11428
xref: UnificationXref11427
left: Complex894
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex898
right: SmallMolecule1166

UnificationXref8456
type: UnificationXref
id: REACT_124032
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_124032.1

Stoichiometry1624
type: Stoichiometry
physical entity: SmallMolecule274
stoichiometric coefficient: 8.0

Stoichiometry1622
type: Stoichiometry
physical entity: Protein1659
stoichiometric coefficient: 2.0

Stoichiometry1623
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

http://identifiers.org/pubmed/19297525
type: PublicationXref
id: 19297525
author: Chacinska, A
author: Stojanovski, D
author: Milenkovic, D
author: Gebert, N
author: Schulze-Specking, A
author: Ramming, T
author: Müller, JM
author: Wenz, LS
author: Rospert, S
db: Pubmed
title: Identification of the signal directing Tim9 and Tim10 into the intermembrane space of mitochondria
source: Mol Biol Cell 20:2530-9
year: 2009

Stoichiometry1620
type: Stoichiometry
physical entity: SmallMolecule278
stoichiometric coefficient: 8.0

Stoichiometry1621
type: Stoichiometry
physical entity: Protein1650
stoichiometric coefficient: 2.0

UnificationXref9944
type: UnificationXref
id: CHEBI:17533
db: ChEBI

UnificationXref9945
type: UnificationXref
id: 30471
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=30471

UnificationXref9946
type: UnificationXref
id: REACT_5708
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5708.2

UnificationXref9947
type: UnificationXref
id: P40360
db: UniProt

UnificationXref9940
type: UnificationXref
id: 5615270
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615270

UnificationXref9941
type: UnificationXref
id: REACT_245225
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_245225.1

UnificationXref9942
type: UnificationXref
id: 5618054
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618054

UnificationXref9943
type: UnificationXref
id: REACT_230831
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_230831.1

UnificationXref8462
type: UnificationXref
id: REACT_124787
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_124787.1

Stimulation of the cell death response by PAK-2p34
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction26
pathway component: BiochemicalReaction25
pathway component: BiochemicalReaction27
evidence: Evidence47
xref: UnificationXref359
xref: UnificationXref360
pathway order: PathwayStep45
pathway order: PathwayStep44
pathway order: PathwayStep43
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

Insertion of correct bases opposite to the lesion by Pol eta
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1776
conversion direction: LEFT_TO_RIGHT
EC number: 2.7.7.7
xref: UnificationXref11477
xref: UnificationXref11476
left: Complex902
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex903

UnificationXref8463
type: UnificationXref
id: 5616789
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616789

Elongation by Pol eta
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1777
conversion direction: LEFT_TO_RIGHT
EC number: 2.7.7.7
xref: UnificationXref11479
xref: UnificationXref11478
left: Complex903
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Note: the coordinates are copied over from Homo sapiens.
right: PhysicalEntity161

UnificationXref8464
type: UnificationXref
id: REACT_250958
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_250958.1

MGMT/hAGT mediated DNA Damage Reversal
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1781
conversion direction: LEFT_TO_RIGHT
EC number: 2.1.1.63
xref: UnificationXref11495
xref: UnificationXref11494
xref: RelationshipXref1470
left: PhysicalEntity163
left: 6-O- methylguanine-DNA methyltransferase
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: 6-O- methylguanine-DNA methyltransferase
right: PhysicalEntity164

UnificationXref8465
type: UnificationXref
id: CHEBI:63540
db: ChEBI

UnificationXref11201
type: UnificationXref
id: 5618564
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618564

UnificationXref11200
type: UnificationXref
id: REACT_178510
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_178510.3

UnificationXref8460
type: UnificationXref
id: CHEBI:63543
db: ChEBI

UnificationXref9959
type: UnificationXref
id: 5608453
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608453

UnificationXref8461
type: UnificationXref
id: 2046065
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2046065

Association of RAD51 with RAD52:DNA double-strand break ends
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1791
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11529
xref: UnificationXref11528
left: Complex907
left: Note: the coordinates are copied over from Homo sapiens.
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex908

UnificationXref11205
type: UnificationXref
id: 936901
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=936901

Association of RAD51 with the resected ends of the DNA double-strand break
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1792
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11531
xref: UnificationXref11532
left: Note: the coordinates are copied over from Homo sapiens.
left: PhysicalEntity15
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex909

UnificationXref11204
type: UnificationXref
id: REACT_189191
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_189191.3

Stoichiometry1639
type: Stoichiometry
physical entity: Protein1671
stoichiometric coefficient: 2.0

Ligation of DNA and formation of Holliday structures following repair synthesis
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1796
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11544
xref: UnificationXref11543
left: PhysicalEntity165
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: PhysicalEntity166

UnificationXref11203
type: UnificationXref
id: 5618520
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618520

UnificationXref11202
type: UnificationXref
id: REACT_189190
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_189190.3

http://identifiers.org/pubmed/11278486
type: PublicationXref
id: 11278486
author: Chong, C
author: Tan, L
author: Lim, L
author: Manser, E
db: Pubmed
title: The mechanism of PAK activation. Autophosphorylation events in both regulatory and kinase domains control activity
source: J Biol Chem 276:17347-53
year: 2001

Intermolecular autophosphorylation of ATM within dimeric ATM complexes
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1783
conversion direction: LEFT_TO_RIGHT
xref: RelationshipXref1472
xref: UnificationXref11502
xref: UnificationXref11501
participant stoichiometry: Stoichiometry2350
participant stoichiometry: Stoichiometry2353
left: SmallMolecule36
left: Complex904
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule37
right: Complex905

UnificationXref11209
type: UnificationXref
id: 5615455
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615455

UnificationXref8466
type: UnificationXref
id: 2046054
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2046054

Stoichiometry1636
type: Stoichiometry
physical entity: SmallMolecule278
stoichiometric coefficient: 8.0

Dissociation of dimeric phospho-ATM complexes
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1784
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11504
xref: UnificationXref11503
participant stoichiometry: Stoichiometry2354
left: Complex905
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Protein604

UnificationXref11208
type: UnificationXref
id: 5615453
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615453

UnificationXref8467
type: UnificationXref
id: REACT_123619
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_123619.1

Stoichiometry1635
type: Stoichiometry
physical entity: Protein1665
stoichiometric coefficient: 2.0

Formation of RAD50:MRE11 complex
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1786
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11513
xref: UnificationXref11512
left: P12753
left: MRE11 homolog 1
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex906

UnificationXref11207
type: UnificationXref
id: P38995
db: UniProt

UnificationXref8468
type: UnificationXref
id: 2046047
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2046047

Stoichiometry1638
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

Association of RAD52 with ssDNA at resected ends of double-strand break
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1790
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11524
xref: UnificationXref11523
left: P06778
left: PhysicalEntity15
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex907

UnificationXref11206
type: UnificationXref
id: REACT_26878
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_26878.2

UnificationXref8469
type: UnificationXref
id: REACT_124358
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_124358.1

Stoichiometry1637
type: Stoichiometry
physical entity: Protein1662
stoichiometric coefficient: 2.0

CHEBI:60629 [ChEBI:60629]
type: SmallMoleculeReference
name: CHEBI:60629
xref: UnificationXref4936

Stoichiometry1631
type: Stoichiometry
physical entity: Protein1665
stoichiometric coefficient: 2.0

CHEBI:60628
type: SmallMoleculeReference
name: CHEBI:60628 [ChEBI:60628]
xref: UnificationXref4925

UnificationXref9950
type: UnificationXref
id: 5608446
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608446

Stoichiometry1632
type: Stoichiometry
physical entity: SmallMolecule274
stoichiometric coefficient: 8.0

CHEBI:60627
type: SmallMoleculeReference
name: CHEBI:60627 [ChEBI:60627]
xref: UnificationXref4942

Stoichiometry1633
type: Stoichiometry
physical entity: Protein1668
stoichiometric coefficient: 2.0

Stoichiometry1634
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

PPi
type: SmallMoleculeReference
name: PPi [ChEBI:29888]
xref: UnificationXref1886

Stoichiometry1630
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

UnificationXref9957
type: UnificationXref
id: P03965
db: UniProt

UnificationXref9958
type: UnificationXref
id: 5608451
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608451

UnificationXref9955
type: UnificationXref
id: 29676
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29676

UnificationXref9956
type: UnificationXref
id: REACT_5535
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5535.2

UnificationXref9953
type: UnificationXref
id: 29896
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29896

UnificationXref9954
type: UnificationXref
id: REACT_2670
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2670.1

UnificationXref9951
type: UnificationXref
id: REACT_255759
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_255759.1

UnificationXref9952
type: UnificationXref
id: 5608447
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608447

http://identifiers.org/pubmed/15585754
type: PublicationXref
id: 15585754
author: Hicklin, DJ
author: Ellis, LM
db: Pubmed
title: Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis
source: J Clin Oncol 23:1011-27
year: 2005

UniProt:Q02939
type: ProteinReference
name: TFB2
xref: UnificationXref3364
organism: http://identifiers.org/taxonomy/4932

HHB is hydroxylated to DHHB by Coq6
type: BiochemicalReaction
data source: Provenance1
conversion direction: LEFT_TO_RIGHT
EC number: 1.14.13
xref: http://identifiers.org/pubmed/21944752
xref: http://identifiers.org/pubmed/12721307
xref: UnificationXref11337
xref: UnificationXref11336
left: SmallMolecule29
left: SmallMolecule27
left: SmallMolecule1160
left: SmallMolecule30
comment: Edited: Williams, MG, 2012-03-23
comment: Reviewed: Kawamukai, Makoto, 2013-02-05
comment: A flavin-dependent monooxygenase involved in ubiquinone/ubiquinol biosynthesis, Coq6 (Heeringa et al. 2011) catalyses the C5-hydroxylation of 3-hexaprenyl-4-hydroxybenzoic acid (HHB) to 3,4-dihydroxy-5-hexaprenylbenzoic acid (DHHB) (Ozeir et al. 2011, Gin et al. 2003). Coq6 is a peripheral membrane protein that localizes to the matrix side of the inner mitochondrial membrane (Gin et al. 2003). Ferredoxin, Yah1 and the ferredoxin reductase, Arh1 may be the in vivo source of electrons for Coq6 and additionally required for this reaction (Ozeir et al. 2011).
comment: Authored: Williams, MG, 2012-03-19
right: SmallMolecule33
right: SmallMolecule1161
right: SmallMolecule31

hOGG1 glycosylase mediated recognition and binding of an 8-oxo guanine opposite to a cytosine
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1743
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11344
xref: UnificationXref11343
left: PhysicalEntity149
left: Note: the coordinates are copied over from Homo sapiens.
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex888

http://identifiers.org/pubmed/11208594
type: PublicationXref
id: 11208594
author: Rabelink, TJ
author: Govers, R
db: Pubmed
title: Cellular regulation of endothelial nitric oxide synthase
source: Am J Physiol Renal Physiol 280:F193-206
year: 2001

Anoctamin transmembrane proteins
type: Protein
data source: Provenance1
member physical entity: ANO9_HUMAN
member physical entity: Note: the coordinates are copied over from Homo sapiens.
member physical entity: ANO1_HUMAN
xref: UnificationXref11260
cellular location: GO_0005886
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5617196
display name: ANOs

ANO1_HUMAN
type: Protein
entity reference: P38250
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: P38250
name: Anoctamin-1
xref: UnificationXref11252
feature: FragmentFeature1894
cellular location: GO_0005886
comment: Reactome DB_ID: 5617188
display name: ANO1

UnificationXref309
type: UnificationXref
id: 5611261
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611261

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38250
data source: Provenance1
name: P38250
name: Anoctamin-2
name: ANO2_HUMAN
xref: UnificationXref11253
feature: FragmentFeature1895
cellular location: GO_0005886
comment: Reactome DB_ID: 5617189
display name: ANO2

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38250
data source: Provenance1
name: P38250
name: ANO3_HUMAN
name: Anoctamin-3
xref: UnificationXref11254
feature: FragmentFeature1896
cellular location: GO_0005886
comment: Reactome DB_ID: 5617190
display name: ANO3

Aminophospholipids are transported from in the internal to the external side of the plasma membrane
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1734
conversion direction: LEFT_TO_RIGHT
EC number: 3.6.3.1
xref: UnificationXref11247
xref: UnificationXref11248
left: SmallMolecule15
left: SmallMolecule1153
left: SmallMolecule12
display name: P-type ATPases type IV transport internal-facing APLs to external side of the plasma membrane
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule54
right: SmallMolecule1150
right: SmallMolecule13

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: DNF2
data source: Provenance1
name: AT8B2_HUMAN
name: Probable phospholipid-transporting ATPase ID
name: Q12675
xref: UnificationXref11239
feature: FragmentFeature1891
cellular location: GO_0005886
comment: Reactome DB_ID: 5615471
display name: ATP8B2

UnificationXref8434
type: UnificationXref
id: REACT_124715
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_124715.1

UnificationXref305
type: UnificationXref
id: 5611260
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611260

Homologues of ATP8B2
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref11241
cellular location: GO_0005886
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5615473

P-type ATPases type IV transport external-facing APLs to internal side of the plasma membrane
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1733
conversion direction: LEFT_TO_RIGHT
EC number: 3.6.3.1
xref: UnificationXref11246
xref: UnificationXref11245
left: SmallMolecule15
left: SmallMolecule1150
left: SmallMolecule12
display name: P-type ATPase type IV subfamily transporters may mediate phospholipid transfer
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule54
right: SmallMolecule13
right: SmallMolecule1153

UnificationXref8433
type: UnificationXref
id: 2046066
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2046066

UnificationXref306
type: UnificationXref
id: 5611252
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611252

CLCN3 exchanges Cl- for H+
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1737
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11268
xref: UnificationXref11269
left: SmallMolecule1156
left: SmallMolecule19
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1053
right: SmallMolecule1034

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: DNF3
data source: Provenance1
name: AT11C_HUMAN
name: Probable phospholipid-transporting ATPase IG
name: Q12674
xref: UnificationXref11243
feature: FragmentFeature1893
cellular location: GO_0005886
comment: Reactome DB_ID: 5615477
display name: ATP11C

UnificationXref8436
type: UnificationXref
id: 2046052
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2046052

UnificationXref307
type: UnificationXref
id: 5611256
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611256

Cytosolic Cl- is transported to extracellular region by ANOs
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1736
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11261
xref: UnificationXref11262
left: SmallMolecule1034
display name: ANOs transport cytosolic Cl- to extracellular region
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1033

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P32660
data source: Provenance1
name: AT8B2_HUMAN
name: Probable phospholipid-transporting ATPase ID
name: P32660
xref: UnificationXref11240
feature: FragmentFeature1892
cellular location: GO_0005886
comment: Reactome DB_ID: 5615472
display name: ATP8B2

UnificationXref8435
type: UnificationXref
id: CHEBI:63545
db: ChEBI

UnificationXref308
type: UnificationXref
id: 5611257
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611257

DMQ6H2 is hydroxylated to DeMQ6H2 by Cat5
type: BiochemicalReaction
data source: Provenance1
conversion direction: LEFT_TO_RIGHT
EC number: 1.14.13
xref: UnificationXref11295
xref: UnificationXref11294
xref: http://identifiers.org/pubmed/16624818
xref: http://identifiers.org/pubmed/8621692
left: SmallMolecule1158
left: SmallMolecule29
left: SmallMolecule27
left: SmallMolecule30
comment: Edited: Williams, MG, 2012-03-23
comment: Reviewed: Kawamukai, Makoto, 2013-02-05
comment: Authored: Williams, MG, 2012-03-19
comment: Catabolite repression protein Cat5 aka ubiquinone biosynthesis protein catalyses the hydroxylation of 2-hexaprenyl-3-methyl-6-methoxy-1,4-benzoquinol (DMQ6H2) to 3-demethylubiquinol-6 (DeMQ6H2) (Marbois & Clarke 1996, Tran et al. 2006).
right: SmallMolecule33
right: SmallMolecule1159
right: SmallMolecule31

UnificationXref11259
type: UnificationXref
id: 5617195
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617195

UnificationXref8438
type: UnificationXref
id: 113601
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113601

UnificationXref301
type: UnificationXref
id: P00045
db: UniProt

http://identifiers.org/pubmed/12123609
type: PublicationXref
id: 12123609
author: Snider, WD
author: Zhong, J
author: Markus, A
db: Pubmed
title: Raf and akt mediate distinct aspects of sensory axon growth
source: Neuron 35:65-76
year: 2002

CLCN4/5/6 exchange Cl- for H+
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1738
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11276
xref: UnificationXref11275
left: SmallMolecule1157
left: SmallMolecule19
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule112
right: SmallMolecule1034

UnificationXref8437
type: UnificationXref
id: REACT_125598
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_125598.1

UnificationXref302
type: UnificationXref
id: 5611258
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611258

Yeast Mcm2-7 mediated fork unwinding
type: BiochemicalReaction
data source: Provenance1
conversion direction: LEFT_TO_RIGHT
xref: http://identifiers.org/pubmed/13679365
xref: http://identifiers.org/pubmed/11136247
xref: http://identifiers.org/pubmed/10980206
xref: http://identifiers.org/pubmed/9305914
xref: http://identifiers.org/pubmed/12480933
xref: http://identifiers.org/pubmed/10834843
xref: UnificationXref11322
xref: UnificationXref11321
left: PhysicalEntity32
comment: Authored: Tye, BK, 2005-11-29 15:49:00
comment: The MCM2-7 complex is the putative replicative helicase that unwinds replication forks. While an S.erevisiae MCM hexameric complex consisting of one copy of each of the six subunits has been reconstituted in vitro from purified subunits (Davey et al. 2003), an active helicase can be assembled with three of the six MCM proteins, MCM4, MCM6 and MCM7, in human (Ishimi,1997), S. pombe (Lee and Hurwitz, 2001) and S. cerevisiae (Kaplan et al., 2003). However, this in vitro reaction may not represent the in vivo situation. In vivo experiments suggest that all six subunits are required at the replication fork (Labib et al., 2000; reviewed by Tye and Sawyer, 2000).
right: PhysicalEntity33

UnificationXref11257
type: UnificationXref
id: 5617193
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617193

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P32660
data source: Provenance1
name: AT8B1_HUMAN
name: P32660
name: Probable phospholipid-transporting ATPase IC
xref: UnificationXref11237
feature: FragmentFeature1890
cellular location: GO_0005886
comment: Reactome DB_ID: 5615469
display name: ATP8B1

UnificationXref303
type: UnificationXref
id: P00044
db: UniProt

MDMQ6H2 is methylated to DMQ6H2 by Coq5
type: BiochemicalReaction
data source: Provenance1
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11300
xref: UnificationXref11299
xref: http://identifiers.org/pubmed/9083049
left: SmallMolecule32
left: SmallMolecule765
comment: Edited: Williams, MG, 2012-03-23
comment: Reviewed: Kawamukai, Makoto, 2013-02-05
comment: 2-methoxy-6-polyprenyl-1,4-benzoquinol methylase, mitochondrial (Coq5) catalyses the C-methyltransferase conversion of 2-hexaprenyl-6-methoxy-1,4-benzoquinol (MDMQ6H2) to 2-hexaprenyl-3-methyl-6-methoxy-1,4-benzoquinol (DMQ6H2) (Barkovich et al. 1997).
comment: Authored: Williams, MG, 2012-03-19
right: SmallMolecule1158
right: SmallMolecule29
right: SmallMolecule767

UnificationXref11258
type: UnificationXref
id: 5617194
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617194

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: DNF2
data source: Provenance1
name: AT8B1_HUMAN
name: Probable phospholipid-transporting ATPase IC
name: Q12675
xref: UnificationXref11235
feature: FragmentFeature1889
cellular location: GO_0005886
comment: Reactome DB_ID: 5615465
display name: ATP8B1

UnificationXref8439
type: UnificationXref
id: REACT_2882
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2882.1

UnificationXref304
type: UnificationXref
id: 5611259
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5611259

UnificationXref11255
type: UnificationXref
id: 5617191
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617191

UnificationXref11256
type: UnificationXref
id: 5617192
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617192

UnificationXref11253
type: UnificationXref
id: 5617189
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617189

UnificationXref11254
type: UnificationXref
id: 5617190
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617190

UnificationXref300
type: UnificationXref
id: GO:0005758
db: GENE ONTOLOGY

UnificationXref11251
type: UnificationXref
id: P38250
db: UniProt

UnificationXref8430
type: UnificationXref
id: 5616783
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616783

UnificationXref11252
type: UnificationXref
id: 5617188
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617188

http://identifiers.org/pubmed/7028108
type: PublicationXref
id: 7028108
author: Olson, RE
author: Goewert, RR
author: Grimm, MF
author: Sippel, CJ
db: Pubmed
title: Identification of 3-methoxy-4-hydroxy-5-hexaprenylbenzoic acid as a new intermediate in ubiquinone biosynthesis by Saccharomyces cerevisiae
source: Biochemistry 20:5611-6
year: 1981

UnificationXref8432
type: UnificationXref
id: REACT_252256
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_252256.1

UnificationXref11250
type: UnificationXref
id: REACT_96459
db: Reactome
id version: 4
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_96459.4

UnificationXref8431
type: UnificationXref
id: 5616785
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616785

http://identifiers.org/pubmed/10958673
type: PublicationXref
id: 10958673
author: Yoshida, H
author: Haze, K
author: Yura, T
author: Yanagi, H
author: Mori, K
author: Okada, T
author: Negishi, M
db: Pubmed
title: ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response
source: Mol Cell Biol 20:6755-67
year: 2000

http://identifiers.org/pubmed/18772128
type: PublicationXref
id: 18772128
author: Riekhof, WR
author: Voelker, DR
author: Gijon, MA
author: Zarini, S
author: Murphy, RC
db: Pubmed
title: Lysophospholipid acyltransferases and arachidonate recycling in human neutrophils
source: J Biol Chem 283:30235-45
year: 2008

UnificationXref11270
type: UnificationXref
id: 2731008
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2731008

http://identifiers.org/pubmed/19935646
type: PublicationXref
id: 19935646
author: Jang, HG
author: Dang, L
author: Keenan, MC
author: Vander Heiden, MG
author: Bennett, BD
author: Rabinowitz, JD
author: Driggers, EM
author: Gross, S
author: Ward, PS
author: Fantin, VR
author: Thompson, CB
author: Cantley, LC
author: Marks, KM
author: White, DW
author: Bittinger, MA
author: Prins, RM
author: Su, SM
author: Yen, KE
author: Liau, LM
author: Jin, S
db: Pubmed
title: Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
source: Nature 462:739-44
year: 2009

Cleavage of uracil by UNG2 glycosylase
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1757
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11409
xref: UnificationXref11410
left: Complex892
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex897
right: SmallMolecule1164

UniProt:P49017
type: ProteinReference
name: COQ5
xref: UnificationXref8794
organism: http://identifiers.org/taxonomy/4932

CAT5
type: Protein
entity reference: ProteinReference1140
data source: Provenance1
name: Catabolite repression protein CAT5
name: CAT5_YEAST
xref: UnificationXref11290
xref: UnificationXref11291
feature: FragmentFeature1905
cellular location: GO_0005743
comment: Reactome DB_ID: 2167845
display name: Cat5

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P37020
data source: Provenance1
name: P37020
name: CLCN4_HUMAN
name: CLCN4
xref: UnificationXref11272
feature: FragmentFeature1903
cellular location: endosome membrane
comment: Reactome DB_ID: 5617203
display name: H

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P37020
data source: Provenance1
name: P37020
name: CLCN5_HUMAN
name: CLCN5
xref: UnificationXref11273
feature: FragmentFeature1904
cellular location: endosome membrane
comment: Reactome DB_ID: 5617204
display name: H

UNG glycosylase mediated recognition and binding of an uracil opposite to a guanine
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1751
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11380
xref: UnificationXref11379
left: PhysicalEntity153
left: Note: the coordinates are copied over from Homo sapiens.
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex892

CLCN4/5/6
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref11274
cellular location: endosome membrane
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5617205

UnificationXref8447
type: UnificationXref
id: 113564
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113564

UnificationXref318
type: UnificationXref
id: P11633
db: UniProt

UNG glycosylase mediated recognition and binding of a 5-hydroxyuracil opposite to a guanine
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1750
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11374
xref: UnificationXref11375
left: PhysicalEntity152
left: Note: the coordinates are copied over from Homo sapiens.
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex891

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P37020
data source: Provenance1
name: CLCN3
name: P37020
name: CLCN3_HUMAN
xref: UnificationXref11267
feature: FragmentFeature1902
cellular location: GO_0031902
comment: Reactome DB_ID: 5617214
display name: H

UnificationXref8446
type: UnificationXref
id: REACT_124125
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_124125.1

UnificationXref319
type: UnificationXref
id: 5613306
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613306

Cleavage of formamidopyrimidine by hOGG1 glycosylase
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1747
conversion direction: LEFT_TO_RIGHT
EC number: 3.2.2.23
xref: UnificationXref11363
xref: UnificationXref11364
left: Complex889
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1163
right: Complex890

ANO9_HUMAN
type: Protein
entity reference: P38250
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Anoctamin-9
name: P38250
xref: UnificationXref11259
feature: FragmentFeature1901
cellular location: GO_0005886
comment: Reactome DB_ID: 5617195
display name: ANO9

UnificationXref8445
type: UnificationXref
id: 2046051
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2046051

UnificationXref316
type: UnificationXref
id: 29428
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29428

Cleavage of 8-oxo guanine by hOGG1 glycosylase
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1746
conversion direction: LEFT_TO_RIGHT
EC number: 3.2.2.23
xref: UnificationXref11358
xref: UnificationXref11359
left: Complex888
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1162
right: Complex890

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38250
data source: Provenance1
name: ANO7_HUMAN
name: P38250
name: Anoctamin-7
xref: UnificationXref11258
feature: FragmentFeature1900
cellular location: GO_0005886
comment: Reactome DB_ID: 5617194
display name: ANO7

UnificationXref8444
type: UnificationXref
id: CHEBI:63542
db: ChEBI

UnificationXref317
type: UnificationXref
id: REACT_3913
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3913.3

hNTH1 glycosylase mediated recognition and binding of thymine glycol
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1755
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11402
xref: UnificationXref11403
left: PhysicalEntity156
left: Homologues of NTHL1
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex896

UnificationXref11268
type: UnificationXref
id: 5617216
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617216

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38250
data source: Provenance1
name: P38250
name: Anoctamin-6
name: ANO6_HUMAN
xref: UnificationXref11257
feature: FragmentFeature1899
cellular location: GO_0005886
comment: Reactome DB_ID: 5617193
display name: ANO6

UnificationXref314
type: UnificationXref
id: REACT_188674
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_188674.3

hNTH1 glycosylase mediated recognition and binding of formamidopyrimidine
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1754
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11398
xref: UnificationXref11397
left: PhysicalEntity150
left: Homologues of NTHL1
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex895

UnificationXref11269
type: UnificationXref
id: REACT_210852
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_210852.2

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38250
data source: Provenance1
name: ANO5_HUMAN
name: P38250
name: Anoctamin-5
xref: UnificationXref11256
feature: FragmentFeature1898
cellular location: GO_0005886
comment: Reactome DB_ID: 5617192
display name: ANO5

UnificationXref315
type: UnificationXref
id: GO:0005654
db: GENE ONTOLOGY

hNTH1 glycosylase mediated recognition and binding of dihydrouracil
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1753
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11395
xref: UnificationXref11394
left: PhysicalEntity155
left: Homologues of NTHL1
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex894

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38250
data source: Provenance1
name: P38250
name: ANO4_HUMAN
name: Anoctamin-4
xref: UnificationXref11255
feature: FragmentFeature1897
cellular location: GO_0005886
comment: Reactome DB_ID: 5617191
display name: ANO4

UnificationXref8449
type: UnificationXref
id: 5616788
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616788

UnificationXref312
type: UnificationXref
id: REACT_188673
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_188673.3

hNTH1 glycosylase mediated recognition and binding of cytosine glycol
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1752
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11390
xref: UnificationXref11389
left: PhysicalEntity154
left: Homologues of NTHL1
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex893

UnificationXref8448
type: UnificationXref
id: REACT_2334
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2334.1

UnificationXref313
type: UnificationXref
id: 5618263
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618263

UnificationXref11264
type: UnificationXref
id: 2731020
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2731020

UnificationXref310
type: UnificationXref
id: REACT_187809
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_187809.3

UnificationXref11265
type: UnificationXref
id: REACT_160470
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160470.1

UnificationXref311
type: UnificationXref
id: 5618262
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618262

UnificationXref11266
type: UnificationXref
id: P37020
db: UniProt

UnificationXref11267
type: UnificationXref
id: 5617214
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617214

hOGG1 glycosylase mediated recognition and binding of a formamidopyrimidine
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1744
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11349
xref: UnificationXref11348
left: PhysicalEntity150
left: Note: the coordinates are copied over from Homo sapiens.
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex889

UnificationXref11260
type: UnificationXref
id: 5617196
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617196

UnificationXref8443
type: UnificationXref
id: REACT_3979
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3979.1

UnificationXref11261
type: UnificationXref
id: 5617198
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617198

UnificationXref8442
type: UnificationXref
id: 159751
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159751

UnificationXref11262
type: UnificationXref
id: REACT_251447
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_251447.1

UnificationXref8441
type: UnificationXref
id: REACT_3165
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3165.1

UnificationXref11263
type: UnificationXref
id: 5617199
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617199

UnificationXref8440
type: UnificationXref
id: 113519
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113519

http://identifiers.org/pubmed/11920679
type: PublicationXref
id: 11920679
author: Fleck, Oliver
author: Kunz, Christophe
author: Marti, Thomas M
db: Pubmed
title: DNA mismatch repair and mutation avoidance pathways
source: J. Cell. Physiol. 191:28-41
year: 2002

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P53397
data source: Provenance1
name: N-glycosylase/DNA lyase
name: P53397
name: N-glycosylase/DNA lyase (Includes: 8-oxoguanine DNA glycosylase (EC 3.2.2.-); DNA-(apurinic or apyrimidinic site) lyase (EC 4.2.99.18) (AP lyase))
name: AP lyase
name: DNA-(apurinic or apyrimidinic site) lyase
name: 8-oxoguanine DNA glycosylase
xref: UnificationXref11341
feature: FragmentFeature1908
cellular location: GO_0005654
comment: Reactome DB_ID: 5610980
display name: OGG1

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P13365
data source: Provenance1
name: UNG2
name: Uracil-DNA glycosylase 2
name: UDG 2
name: P13365
name: Uracil-DNA glycosylase 2 (EC 3.2.2.-)
xref: UnificationXref11370
feature: FragmentFeature1909
cellular location: GO_0005654
comment: Reactome DB_ID: 5610945
display name: CCNO

FATP1, 4 and 6 can mediate the influx of long chain fatty acids into cells
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1710
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11132
xref: UnificationXref11131
left: SmallMolecule1141
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1143

UnificationXref8419
type: UnificationXref
id: 2046056
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2046056

Aquaporins passively transport water into cells
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1714
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11164
xref: UnificationXref11163
left: SmallMolecule349
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule15

Aquaporins passively transport water out of cells
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1715
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11166
xref: UnificationXref11165
left: SmallMolecule15
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule349

Aquaporins passively transport glycerol into cells
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1716
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11170
xref: UnificationXref11171
left: SmallMolecule1145
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule18

yMcm2
type: Protein
entity reference: ProteinReference1142
data source: Provenance1
xref: UnificationXref11303
xref: UnificationXref11302
cellular location: GO_0005654
comment: Reactome DB_ID: 169497

UnificationXref11237
type: UnificationXref
id: 5615469
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615469

AT1 transports acetyl-CoA into the Golgi lumen
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1706
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11106
xref: UnificationXref11105
left: SmallMolecule267
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1137

UnificationXref8416
type: UnificationXref
id: 5618126
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618126

UnificationXref323
type: UnificationXref
id: 5613310
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613310

COQ5_YEAST
type: Protein
entity reference: ProteinReference1141
data source: Provenance1
name: 2-methoxy-6-polyprenyl-1,4-benzoquinol methylase, mitochondrial ecNumber2.1.1.201/ecNumber
name: COQ5
xref: UnificationXref11298
xref: UnificationXref11297
feature: FragmentFeature1906
cellular location: GO_0005759
comment: Reactome DB_ID: 2167839
display name: Coq5

UnificationXref11238
type: UnificationXref
id: 5615470
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615470

Equilibrative transport (import) of adenosine and biogenic amines by solute carrier family 29 (nucleoside transporters), member 4
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1704
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11094
xref: UnificationXref11095
left: SmallMolecule1132
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1127

UnificationXref8415
type: UnificationXref
id: REACT_188956
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_188956.3

UnificationXref324
type: UnificationXref
id: REACT_249921
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_249921.1

yMcm4
type: Protein
entity reference: ProteinReference1144
data source: Provenance1
xref: UnificationXref11309
xref: UnificationXref11308
cellular location: GO_0005654
comment: Reactome DB_ID: 169496

UnificationXref11235
type: UnificationXref
id: 5615465
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615465

SLC35B4 mediates the transport of UDP-N-acetylglucosamine into the Golgi lumen
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1708
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11118
xref: UnificationXref11119
left: SmallMolecule271
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1140

UnificationXref8418
type: UnificationXref
id: CHEBI:27432
db: ChEBI

UnificationXref325
type: UnificationXref
id: 5618453
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618453

yMcm5
type: Protein
entity reference: ProteinReference1143
data source: Provenance1
xref: UnificationXref11305
xref: UnificationXref11306
cellular location: GO_0005654
comment: Reactome DB_ID: 169511

UnificationXref11236
type: UnificationXref
id: P32660
db: UniProt

SLC35B4 mediates the transport of UDP-xylose into the Golgi lumen
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1707
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11114
xref: UnificationXref11115
left: SmallMolecule1138
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1139

UnificationXref8417
type: UnificationXref
id: REACT_191567
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_191567.3

UnificationXref326
type: UnificationXref
id: REACT_238512
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_238512.1

yMcm3
type: Protein
entity reference: ProteinReference1146
data source: Provenance1
xref: UnificationXref11315
xref: UnificationXref11314
cellular location: GO_0005654
comment: Reactome DB_ID: 169513

UnificationXref8412
type: UnificationXref
id: 5618612
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618612

UnificationXref327
type: UnificationXref
id: 5618454
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618454

yMcm7
type: Protein
entity reference: ProteinReference1145
data source: Provenance1
xref: UnificationXref11312
xref: UnificationXref11311
cellular location: GO_0005654
comment: Reactome DB_ID: 169505

UnificationXref8411
type: UnificationXref
id: REACT_181502
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_181502.3

UnificationXref328
type: UnificationXref
id: REACT_251784
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_251784.1

COQ6_YEAST
type: Protein
entity reference: ProteinReference1148
data source: Provenance1
name: Ubiquinone biosynthesis monooxygenase COQ6 ecNumber1.14.13.-/ecNumber
name: COQ6
xref: UnificationXref11333
xref: UnificationXref11332
feature: FragmentFeature1907
cellular location: GO_0005743
comment: Reactome DB_ID: 2162276
display name: Coq6

UnificationXref11239
type: UnificationXref
id: 5615471
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615471

Equilibrative transport (export) of adenosine and biogenic amines by solute carrier family 29 (nucleoside transporters), member 4
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1703
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11093
xref: UnificationXref11092
left: SmallMolecule1127
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1132

UnificationXref8414
type: UnificationXref
id: 5618611
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618611

UnificationXref329
type: UnificationXref
id: Q03497
db: UniProt

yMcm6
type: Protein
entity reference: ProteinReference1147
data source: Provenance1
xref: UnificationXref11317
xref: UnificationXref11318
cellular location: GO_0005654
comment: Reactome DB_ID: 169504

Equilibrative transport (import) of nucleosides and adenine by solute carrier family 29 (nucleoside transporters), member 3
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1702
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11067
xref: UnificationXref11068
left: SmallMolecule1126
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1118

UnificationXref8413
type: UnificationXref
id: REACT_188958
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_188958.3

S000006034
type: ProteinReference
name: UniProt:Q02961
xref: UnificationXref10125
organism: http://identifiers.org/taxonomy/4932

UnificationXref11230
type: UnificationXref
id: REACT_25925
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_25925.2

UnificationXref8410
type: UnificationXref
id: 5616352
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616352

UnificationXref11233
type: UnificationXref
id: 5615461
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615461

UnificationXref11234
type: UnificationXref
id: Q12675
db: UniProt

UnificationXref320
type: UnificationXref
id: 5613307
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613307

UnificationXref11231
type: UnificationXref
id: 5615457
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615457

UnificationXref321
type: UnificationXref
id: 5613308
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613308

UnificationXref11232
type: UnificationXref
id: P39524
db: UniProt

UnificationXref322
type: UnificationXref
id: 5613309
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613309

http://identifiers.org/pubmed/19935667
type: PublicationXref
id: 19935667
author: Hall, RA
author: Ritter, SL
db: Pubmed
title: Fine-tuning of GPCR activity by receptor-interacting proteins
source: Nat Rev Mol Cell Biol 10:819-30
year: 2009

COPII (Coat Protein 2) Mediated Vesicle Transport
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction387
pathway component: BiochemicalReaction389
pathway component: BiochemicalReaction388
pathway component: BiochemicalReaction390
pathway component: BiochemicalReaction391
evidence: Evidence732
xref: RelationshipXref424
xref: UnificationXref5053
xref: UnificationXref5054
pathway order: PathwayStep715
pathway order: PathwayStep716
pathway order: PathwayStep717
pathway order: PathwayStep718
pathway order: PathwayStep719
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

P12753
type: Protein
entity reference: ProteinReference1157
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref11508
feature: FragmentFeature1918
cellular location: GO_0005654
comment: Reactome DB_ID: 5610504
display name: RAD50

Calcium is sequestered to the golgi by secretory pathway calcium-ATPases (SPCAs)
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1732
conversion direction: LEFT_TO_RIGHT
EC number: 3.6.3.8
xref: UnificationXref11218
xref: UnificationXref11219
left: SmallMolecule15
left: SmallMolecule9
left: SmallMolecule12
display name: ATP2C1/2:Mg2+ transport cytosolic Ca2+ to Golgi lumen
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule54
right: SmallMolecule1149
right: SmallMolecule13

Acidification of Tf:TfR1 containing endosome
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1728
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11199
xref: UnificationXref11200
participant stoichiometry: Stoichiometry2304
participant stoichiometry: Stoichiometry2305
left: SmallMolecule19
left: SmallMolecule15
left: SmallMolecule12
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule112
right: SmallMolecule54
right: SmallMolecule13

Copper sequestration by copper-transporting ATPase 2
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1731
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11210
xref: UnificationXref11209
left: SmallMolecule323
left: SmallMolecule15
left: SmallMolecule12
display name: ATP7B transports cytosolic Cu2+ to Golgi lumen
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule54
right: SmallMolecule1148
right: SmallMolecule13

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P12689
data source: Provenance1
name: P12689
name: DNA repair protein REV1 ecNumber2.7.7.-/ecNumber
name: REV1_HUMAN
xref: UnificationXref11451
feature: FragmentFeature1913
cellular location: GO_0005654
comment: Reactome DB_ID: 5610993
display name: REV1

UnificationXref11246
type: UnificationXref
id: REACT_182172
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_182172.3

Export of heme to the blood by ABCG2
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1727
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11198
xref: UnificationXref11197
left: SmallMolecule117
left: SmallMolecule15
left: SmallMolecule12
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule54
right: SmallMolecule1147
right: SmallMolecule13

UnificationXref8429
type: UnificationXref
id: REACT_122430
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_122430.1

UnificationXref336
type: UnificationXref
id: 5613165
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613165

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P26793
data source: Provenance1
name: Maturation factor 1
name: P26793
name: FEN1
name: Flap endonuclease-1
xref: UnificationXref11438
feature: FragmentFeature1912
cellular location: GO_0005654
comment: Reactome DB_ID: 5611019
display name: MF1

UnificationXref11247
type: UnificationXref
id: 5615496
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615496

Aquaporin-9 passively transports glycerol into cell
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1724
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11190
xref: UnificationXref11189
left: SmallMolecule1145
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule18

UnificationXref8428
type: UnificationXref
id: 2046049
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2046049

UnificationXref337
type: UnificationXref
id: 5613167
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613167

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: Q08214
data source: Provenance1
name: Q08214
name: Endonuclease III-like protein 1 (EC 4.2.99.18)
name: hNTH1
name: Endonuclease III-like protein 1
xref: UnificationXref11384
feature: FragmentFeature1911
cellular location: GO_0005654
comment: Reactome DB_ID: 5610957
display name: NTHL1

UnificationXref11248
type: UnificationXref
id: REACT_182160
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_182160.3

Aquaporin-7 passively transports glycerol out of cell
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1723
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11188
xref: UnificationXref11187
left: SmallMolecule18
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1145

UnificationXref8427
type: UnificationXref
id: REACT_121476
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_121476.1

UnificationXref334
type: UnificationXref
id: 5613162
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613162

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P31378
data source: Provenance1
name: Endonuclease III-like protein 1 (EC 4.2.99.18)
name: hNTH1
name: P31378
name: Endonuclease III-like protein 1
xref: UnificationXref11382
feature: FragmentFeature1910
cellular location: GO_0005654
comment: Reactome DB_ID: 5610953
display name: NTHL1

UnificationXref11249
type: UnificationXref
id: 5618494
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618494

Aquaporin-3 passively transports water out of cell
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1721
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11184
xref: UnificationXref11183
left: SmallMolecule15
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule349

UnificationXref8426
type: UnificationXref
id: 2046062
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2046062

UnificationXref335
type: UnificationXref
id: 5613163
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613163

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38110
data source: Provenance1
name: Ataxia telangiectasia mutated
name: P38110
name: Serine-protein kinase ATM
name: A-T, mutated
name: ATM serine-protein kinase
name: Serine-protein kinase ATM (EC 2.7.1.37) (Ataxia telangiectasia mutated) (A-T, mutated)
xref: UnificationXref11498
feature: FragmentFeature1917
cellular location: GO_0005654
comment: Reactome DB_ID: 5610497
display name: ATM

Aquaporins passively transport urea out of cells
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1719
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11180
xref: UnificationXref11179
left: SmallMolecule933
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1146

UnificationXref8425
type: UnificationXref
id: CHEBI:51985
db: ChEBI

http://identifiers.org/pubmed/11988738
type: PublicationXref
id: 11988738
author: Lukas, J
author: Jackson, PK
author: Reimann, JD
author: Sorensen, CS
author: Hsu, JY
db: Pubmed
title: E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1)
source: Nat Cell Biol 4:358-66
year: 2002

6-O- methylguanine-DNA methyltransferase
type: Protein
entity reference: P26188
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: MGMT containing S-methyl-L-cysteine
name: Methylated-DNA--protein-cysteine methyltransferase
name: MetC-MGMT
xref: UnificationXref11493
feature: FragmentFeature1916
feature: ModificationFeature341
cellular location: GO_0005654
comment: Reactome DB_ID: 5610093
display name: P26188

Aquaporins passively transport urea into cells
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1718
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11178
xref: UnificationXref11177
left: SmallMolecule1146
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule933

UnificationXref8424
type: UnificationXref
id: REACT_122294
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_122294.1

6-O- methylguanine-DNA methyltransferase
type: Protein
entity reference: P26188
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Methylated-DNA--protein-cysteine methyltransferase
name: P26188
name: Methylated-DNA--protein-cysteine methyltransferase (EC 2.1.1.63) (6-O- methylguanine-DNA methyltransferase)
xref: UnificationXref11487
feature: FragmentFeature1915
cellular location: GO_0005654
comment: Reactome DB_ID: 5610091
display name: MGMT

Aquaporins passively transport glycerol out of cells
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1717
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11173
xref: UnificationXref11172
left: SmallMolecule18
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1145

UnificationXref8423
type: UnificationXref
id: 2046064
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2046064

UnificationXref338
type: UnificationXref
id: 5613169
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613169

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: Q04049
data source: Provenance1
name: Q04049
name: DNA polymerase eta
name: Pol eta protein
xref: UnificationXref11469
feature: FragmentFeature1914
cellular location: GO_0005654
comment: Reactome DB_ID: 5611004
display name: POLH

UnificationXref8422
type: UnificationXref
id: REACT_119727
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119727.1

UnificationXref339
type: UnificationXref
id: 5613170
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613170

UnificationXref8421
type: UnificationXref
id: 211579
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=211579

UnificationXref8420
type: UnificationXref
id: REACT_121509
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_121509.1

UnificationXref11240
type: UnificationXref
id: 5615472
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615472

UnificationXref11241
type: UnificationXref
id: 5615473
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615473

Homologues of NTHL1
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref11385
cellular location: GO_0005654
comment: Reactome DB_ID: 5610958
comment: Converted from EntitySet in Reactome

UnificationXref11242
type: UnificationXref
id: Q12674
db: UniProt

UnificationXref332
type: UnificationXref
id: 5613161
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613161

UnificationXref11243
type: UnificationXref
id: 5615477
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615477

UnificationXref333
type: UnificationXref
id: Q12469
db: UniProt

UnificationXref11244
type: UnificationXref
id: 5615478
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615478

UnificationXref330
type: UnificationXref
id: 5613160
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613160

UnificationXref11245
type: UnificationXref
id: 5615480
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615480

UnificationXref331
type: UnificationXref
id: P48562
db: UniProt

SLC29A1
type: Protein
entity reference: P31381
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Equilibrative nucleoside transporter 1
name: Equilibrative NBMPR-sensitive nucleoside transporter
name: P31381
name: Equilibrative nitrobenzylmercaptopurine riboside-sensitive nucleoside transporter
name: solute carrier family 29 (nucleoside transporters), member 1
name: Equilibrative nucleoside transporter 1 (Equilibrative nitrobenzylmercaptopurine riboside-sensitive nucleoside transporter) (Equilibrative NBMPR-sensitive nucleoside transporter) (Nucleoside transporter, es-type)
name: Nucleoside transporter, es-type
xref: UnificationXref11018
feature: FragmentFeature1866
cellular location: GO_0005886
comment: Reactome DB_ID: 5610770
display name: ENT1

HMIT co-transports myo-inositol with a proton
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1680
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10887
xref: UnificationXref10886
left: SmallMolecule1075
left: SmallMolecule1048
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule19
right: SmallMolecule497

SLC29A1-like proteins
type: Protein
data source: Provenance1
member physical entity: SLC29A1
xref: UnificationXref11019
cellular location: GO_0005886
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5610771

GLUT9 transports glucose, fructose and urate
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1677
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10872
xref: UnificationXref10871
left: SmallMolecule1071
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1073

36 kDa nucleolar protein HNP36
type: Protein
entity reference: P31381
data source: Provenance1
name: Equilibrative nucleoside transporter 2 (Equilibrative nitrobenzylmercaptopurine riboside-insensitive nucleoside transporter) (Equilibrative NBMPR-insensitive nucleoside transporter) (Nucleoside transporter, ei-type) (36 kDa nucleolar protein HNP36) (Hydrophobic nucleolar protein, 36 kDa) (Delayed-early response protein 12)
name: solute carrier family 29 (nucleoside transporters), member 2
name: Hydrophobic nucleolar protein, 36 kDa
name: Equilibrative nucleoside transporter 2
name: Note: the coordinates are copied over from Homo sapiens.
name: SLC29A2
name: Delayed-early response protein 12
name: P31381
name: Equilibrative nitrobenzylmercaptopurine riboside-insensitive nucleoside transporter
name: Nucleoside transporter, ei-type
name: Equilibrative NBMPR-insensitive nucleoside transporter
xref: UnificationXref11039
feature: FragmentFeature1867
cellular location: GO_0005886
comment: Reactome DB_ID: 5610761
display name: ENT2

NaS2 co-transports sulphate and two sodium ions
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1683
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10898
xref: UnificationXref10899
participant stoichiometry: Stoichiometry2296
participant stoichiometry: Stoichiometry2295
left: SmallMolecule1076
left: SmallMolecule1047
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule377
right: SmallMolecule1046

SLC29A2-like proteins
type: Protein
data source: Provenance1
member physical entity: 36 kDa nucleolar protein HNP36
xref: UnificationXref11040
cellular location: GO_0005886
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5610762

NaS1 co-transports sulphate and a sodium ion
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1682
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10894
xref: UnificationXref10895
left: SmallMolecule1076
left: SmallMolecule1047
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule377
right: SmallMolecule1046

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P32798
data source: Provenance1
name: Zinc transporter 1
name: SLC30A1
name: P32798
name: ZNT1_HUMAN
xref: UnificationXref10978
feature: FragmentFeature1863
cellular location: GO_0005886
comment: Reactome DB_ID: 5614418
display name: ZnT1

NaDC3 co-transports the dicarboxylic acid succinate and three sodium ion
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1685
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10911
xref: UnificationXref10912
participant stoichiometry: Stoichiometry2297
participant stoichiometry: Stoichiometry2298
left: SmallMolecule1079
left: SmallMolecule1047
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule939
right: SmallMolecule1046

Homologues of SLC30A1
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref10981
cellular location: GO_0005886
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5614423

NaDC1 co-transports dicarboxylic acids and a sodium ion
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1684
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10907
xref: UnificationXref10908
left: SmallMolecule1047
left: SmallMolecule1077
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1080
right: SmallMolecule1046

P40544
type: Protein
entity reference: P40544
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: SLC39A7
name: S39A7_HUMAN
name: HKE4
name: Zinc transporter SLC39A7
xref: UnificationXref10989
feature: FragmentFeature1865
cellular location: GO_0005789
comment: Reactome DB_ID: 5614448
display name: ZIP7

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: ZRC1
data source: Provenance1
name: P20107
name: Zinc transporter 1
name: SLC30A1
name: ZNT1_HUMAN
xref: UnificationXref10980
feature: FragmentFeature1864
cellular location: GO_0005886
comment: Reactome DB_ID: 5614422
display name: ZnT1

Evidence319
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15976490
xref: http://identifiers.org/pubmed/14751757
xref: http://identifiers.org/pubmed/12893815
xref: http://identifiers.org/pubmed/15585605
xref: http://identifiers.org/pubmed/15950447
comment: In human, ten members of the Toll-like receptor (TLR) family (TLR1-TLR10) have been identified (TLR11 has been found in mouse, but not in human). All TLRs have a similar Toll/IL-1 receptor (TIR) domain in their cytoplasmic region and an Ig-like domain in the extracellular region, where each is enriched with a varying number of leucine-rich repeats (LRRs). Each TLR can recognize specific microbial pathogen components. The binding pathogenic component to TLR initializes signaling pathways that lead to induction of Interferon alpha/beta and inflammatory cytokines. There are two main signaling pathways. The first is a MyD88-dependent pathway that is common to all TLRs, except TLR3; the second is a TRIF(TICAM1)-dependent pathway that is peculiar to TLR3 and TLR4. TLR4-mediated signaling pathway via TRIF requires adapter molecule TRAM (TRIF-related adapter molecule or TICAM2). TRAM is thought to bridge between the activated TLR4 complex and TRIF.(Takeda & Akira 2004; Akira 2003; Takeda & Akira 2005; Kawai 2005; Heine & Ulmer 2005).

RNA Polymerase II Transcription Initiation And Promoter Clearance
type: Pathway
data source: Provenance1
pathway component: REACT 257112.1
pathway component: REACT 249293.1
pathway component: BiochemicalReaction230
evidence: Evidence513
xref: UnificationXref3466
xref: UnificationXref3467
pathway order: PathwayStep499
pathway order: PathwayStep504
pathway order: PathwayStep495
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

Evidence311
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: PublicationXref747
xref: http://identifiers.org/pubmed/11130078
xref: http://identifiers.org/pubmed/9799232
xref: http://identifiers.org/pubmed/14751759
xref: http://identifiers.org/pubmed/7700380
xref: http://identifiers.org/pubmed/11470918
xref: http://identifiers.org/pubmed/11564765
comment: CpG DNA is an unusual Pathogen-Associated Molecular Pattern (PAMP). Cytosine methylation exists in mammalian but not bacterial cells, and most (but not all) CpG in the mammalian genome is methylated. Therefore, unmethylated CpG DNA may signal the presence of microbial infection. Evidence of CpG recognition by TLR9 was demonstrated both in human and mouse, and this type of signaling requires its internalization into late endosomal/lysosomal compartments. TLR9 has been reported to be able to discern different types of CpG motifs, and therefore that it presumably recognizes CpG DNA directly. It appears that over evolutionary periods, TLR9 molecules expressed by different species have diverged. This has led to differences in the precise sequence motif (CpG dinucleotide plus flanking regions) that optimally stimulate the innate immune system of different animals.

UnificationXref11299
type: UnificationXref
id: 2167836
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2167836

Evidence312
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18222170
xref: http://identifiers.org/pubmed/16757566
xref: http://identifiers.org/pubmed/18297073
comment: TRIF-related adapter molecule (TRAM or also known as TICAM2) is a sorting adapter which recruits TRIF to activated TLR4. Like TLR4, TRAM was detected both at the plasma membrane and in the endosomal compartment. TRAM was reported to recruit TRIF to the plasma membrane [Tanimuro N et al 2008]. However, TRAM did not induce TRIF-mediated signaling from the cell surface, instead, TRAM endocytosis was required for activation of IRF3 and induction of IFN-beta [Tanimuro N et al 2008; Kagan JC et al 2008]. Although, endocytosis of both TLR4 and TRAM and their association are required to trigger TRIF-mediated signaling, TRAM can target endosomes independently on its interaction with TLR4. TRAM cellular localization is controlled by myristoylation and phosphorylation of its N-terminal bipartite sorting signal motif [Kagan JC et al 2008]. TRAM has been shown to undergo phosphorylation on Ser-16 by protein kinase C epsilon in LPS-treated human THP1 and murine embryonic fibroblasts (MEF) cells [McGettrick AF et al 2006].

UniProt:Q00684
type: ProteinReference
name: CDC14
xref: UnificationXref1889
organism: http://identifiers.org/taxonomy/4932

UnificationXref11298
type: UnificationXref
id: REACT_160876
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160876.1

Evidence313
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15276183
comment: The first known downstream component of TLR4 and TLR2 signaling is the adaptor MyD88. Another adapter MyD88-adaptor-like (Mal; also known as TIR-domain-containing adaptor protein or TIRAP) has also been described for TLR4 and TLR2 signaling. MyD88 comprises an N-terminal Death Domain (DD) and a C-terminal TIR, whereas Mal lacks the DD. The TIR homotypic interactions bring adapters into contact with the activated TLRs, whereas the DD modules recruit serine/threonine kinases such as interleukin-1-receptor-associated kinase (IRAK). Recruitment of these protein kinases is accompanied by phosphorylation, which in turn results in the interaction of IRAKs with TNF-receptor-associated factor 6 (TRAF6). The oligomerization of TRAF6 activates TAK1, a member of the MAP3-kinase family, and this leads to the activation of the IkB kinases. These kinases, in turn, phosphorylate IkB, leading to its proteolytic degradation and the translocation of NF-kB to the nucleus. Concomitantly, members of the activator protein-1 (AP-1) transcription factor family, Jun and Fos, are activated, and both AP-1 transcription factors and NF-kB are required for cytokine production, which in turn produces downstream inflammatory effects.

http://identifiers.org/pubmed/1644792
type: PublicationXref
id: 1644792
author: Jhon, DY
author: Rhee, SG
author: Kriz, R
author: Knopf, J
author: Park, D
db: Pubmed
title: Cloning, sequencing, expression, and Gq-independent activation of phospholipase C-beta 2
source: J Biol Chem 267:16048-55
year: 1992

UnificationXref11297
type: UnificationXref
id: 2167839
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2167839

Evidence314
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/14556004
xref: http://identifiers.org/pubmed/15276183
xref: http://identifiers.org/pubmed/18222170
xref: http://identifiers.org/pubmed/18297073
xref: http://identifiers.org/pubmed/15588429
xref: http://identifiers.org/pubmed/15596121
xref: http://identifiers.org/pubmed/15845500
xref: http://identifiers.org/pubmed/22078883
comment: TLR4 is unique among the TLR family in its ability to recruit four adapters to activate two distinct signaling pathways. One pathway is activated by the pair of the adapters Mal or TIRAP (Toll/interleukin-1-receptor (TIR)-domain-containing adapter protein) and MyD88, which leads to the NFkB activation and the induction of pro-inflammatory cytokines. The second pathway is activated by the adapters TRIF (TIR-domain-containing adapter protein inducing interferon-beta) and TRAM (TRIF-related adapter molecule). The combined use of TRIF and TRAM adapters is specific for TLR4 signaling pathway and leads to the induction of type I interferons and delayed activation of NFkB. The previous model of TLR4 signaling pathway described the simultaneous activation of these two signaling pathways at the plasma membrane, however the later studies suggested that upon activation TLR4 first induces TIRAP-MyD88 signaling at the plasma membrane and is then endocytosed and activates TRAM-TRIF signaling from the early endosome [Kagan JC et al 2008; Tanimura N et al 2008; Zanoni I et al 2011].

UnificationXref11296
type: UnificationXref
id: P49017
db: UniProt

Evidence315
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Toll-like Receptor 4 is a Microbe Associated Molecular Pattern receptor well known for it's sensitivity to Bacterial Lipopolysaccharides (LPS). LPS is assembled within diverse Gram-negative bacteria, many of which are human or plant pathogens. It is a component of the outer membrane of Gram-negative bacteria and consists of lipid A, a core polysaccharide and an O-polysaccharide of variable length (often more than 50 monosaccharide units). LPS is a potent activator of the innate immune response in humans, causing reactions including fever, headache, nausea, diarrhoea, changes in leukocyte and platelet counts, disseminated intravascular coagulation, multiorgan failure, shock and death. All these reactions are induced by cytokines and other endogenous mediators which are produced after interaction of LPS with the humoral and cellular targets of the host. In macrophages and dendritic cells, LPS-mediated activation of TLR4 triggers the biosynthesis of diverse mediators of inflammation, such as TNF-alpha and IL6, and activates the production of co-stimulatory molecules required for the adaptive immune response. In mononuclear and endothelial cells, LPS also stimulates tissue factor production. These events are desirable for clearing local infections, but when these various mediators and clotting factors are overproduced, they can damage small blood vessels and precipitate shock accompanied by disseminated intravascular coagulation and multiple organ failure.

UnificationXref11295
type: UnificationXref
id: REACT_160197
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160197.1

Evidence316
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12975352
comment: TLR1 is expressed by monocytes. TLR1 and TLR2 cotranslationally form heterodimeric complexes on the cell surface and in the cytosol. The TLR2:TLR1 complex recognizes Neisserial PorB and Mycobacterial triacylated lipoproteins and peptides, amongst others, triggering up-regulation of nuclear factor-kappaB production and apoptotic cascades. Such cooperation between TLR1 and TLR2 on the cell surface of normal human peripheral blood mononuclear cells, for instance, leads to the activation of pro-inflammatory cytokine secretion (Sandor et al. 2003).

UnificationXref11294
type: UnificationXref
id: 2167856
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2167856

Evidence317
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/14977973
comment: TLR2 and TLR4 recognize different bacterial cell wall components. While TLR4 is trained onto Gram-negative lipopolysaccharide components, TLR2 - in combination with TLR6 - plays a major role in recognizing peptidoglycan wall products from Gram-positive bacteria, as well as Mycobacterial diacylated lipopeptides. In particular, TLR6 appears to participate in discriminating the subtle differences between dipalmitoyl and tripalmitoyl cysteinyl residues (Okusawa et al. 2004).

UnificationXref11293
type: UnificationXref
id: REACT_161144
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_161144.1

Evidence318
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10820283
comment: TLR2 is involved in recognition of peptidoglycan from gram-positive bacteria, bacterial lipoproteins, mycoplasma lipoprotein and mycobacterial products. It is quite possible that recognition of at least some other TLR2 ligands may be assisted by additional accessory proteins, particularly in association with TLR1 or TLR6. TLR2 is expressed constitutively on macrophages, dendritic cells, and B cells, and can be induced in some other cell types, including epithelial cells. TLR1 and TLR6, on the other hand, are expressed almost ubiquitously (Muzio et al. 2000). TLR2 may be a sensor and inductor of specific defense processes, including oxidative stress and cellular necrosis initially spurred by microbial compounds.

tRNA Aminoacylation
type: Pathway
data source: Provenance1
pathway component: REACT 259818.1
pathway component: REACT 256513.1
evidence: Evidence587
xref: UnificationXref4110
xref: RelationshipXref288
xref: UnificationXref4109
pathway order: PathwayStep576
pathway order: PathwayStep555
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

Q12078
type: Protein
entity reference: Q12078
data source: Provenance1
name: SLC11A2
name: Note: the coordinates are copied over from Homo sapiens.
name: NRAM2_HUMAN
name: Natural resistance-associated macrophage protein 2
name: NRAMP2
xref: UnificationXref10969
feature: FragmentFeature1861
cellular location: GO_0005886
comment: Reactome DB_ID: 5614407
display name: DCT1

SLC11A2
type: Protein
entity reference: P38778
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: NRAM2_HUMAN
name: Natural resistance-associated macrophage protein 2
name: P38778
name: NRAMP2
xref: UnificationXref10971
feature: FragmentFeature1862
cellular location: GO_0005886
comment: Reactome DB_ID: 5614411
display name: DCT1

SLC7A9-mediated exchange of extracellular arginine, lysine, or cystine for cytosolic leucine
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1669
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10831
xref: UnificationXref10832
left: SmallMolecule1060
left: SmallMolecule86
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1062
right: SmallMolecule1008

Vesicular inhibitory amino acid transport
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1673
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10851
xref: UnificationXref10850
left: SmallMolecule1064
left: SmallMolecule1065
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule19
right: SmallMolecule1066

Glucose transport by class I GLUTs
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1675
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10855
xref: UnificationXref10856
left: SmallMolecule388
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule393

GLUT7 and GLUT11 transport glucose and fructose
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1676
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10861
xref: UnificationXref10862
left: SmallMolecule1069
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1070

Evidence310
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/14976262
comment: RNA can serve as a danger signal, both in its double-stranded form (that is associated with viral infection), as well as single-stranded RNA (ssRNA). Specifically, guanosine (G)- and uridine (U)-rich ssRNA oligonucleotides derived from human immunodeficiency virus-1 (HIV-1), for example, stimulate dendritic cells (DC) and macrophages to secrete interferon-alpha and proinflammatory, as well as regulatory, cytokines. This has been found to be mediated by TLR7, as well as TLR8. Separate studies showed that imidazoquinoline compounds (e.g. imiquimod and R-848, low-molecular-weight immune response modifiers that can induce the synthesis of interferon-alpha) also exert their effects in a MyD88-dependent fashion independently through TLR7 and 8 (Heil et al. 2004).

Equilibrative transport (import) of nucleosides and free bases by solute carrier family 29 (nucleoside transporters), member 2
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1700
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11045
xref: UnificationXref11046
left: SmallMolecule1111
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1109

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P23900
data source: Provenance1
name: Aquaporin-3
name: AQP3_HUMAN
name: P23900
xref: UnificationXref11140
feature: FragmentFeature1874
cellular location: GO_0005886
comment: Reactome DB_ID: 5614527
display name: AQP3

Equilibrative transport (import) of nucleosides and free bases by solute carrier family 29 (nucleoside transporters), member 1
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1699
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11043
xref: UnificationXref11044
left: SmallMolecule1102
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1100

Homologues of AQP3
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref11143
cellular location: GO_0005886
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5614529

Equilibrative transport (export) of nucleosides and free bases by solute carrier family 29 (nucleoside transporters), member 2
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1698
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11041
xref: UnificationXref11042
left: SmallMolecule1109
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1111

UnificationXref8409
type: UnificationXref
id: REACT_180355
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_180355.3

Metabolism of vitamins and cofactors
type: Pathway
data source: Provenance1
pathway component: REACT 241955.1
evidence: Evidence1492
xref: RelationshipXref1172
xref: UnificationXref9670
xref: UnificationXref9671
pathway order: PathwayStep1037
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

S27A4_HUMAN
type: Protein
entity reference: P38225
data source: Provenance1
name: Long-chain fatty acid transport protein 4
name: Note: the coordinates are copied over from Homo sapiens.
name: P38225
name: SLC27A4
xref: UnificationXref11129
feature: FragmentFeature1873
cellular location: GO_0005886
comment: Reactome DB_ID: 5615220
display name: FATP4

Equilibrative transport (export) of nucleosides and free bases by solute carrier family 29 (nucleoside transporters), member 1
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1697
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11021
xref: UnificationXref11020
left: SmallMolecule1100
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1102

UnificationXref8408
type: UnificationXref
id: 5616420
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616420

FATP1/4/6
type: Protein
data source: Provenance1
member physical entity: S27A4_HUMAN
member physical entity: Protein1870
xref: UnificationXref11130
cellular location: GO_0005886
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5615221

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P40004
data source: Provenance1
name: S35B4_HUMAN
name: P40004
name: UDP-xylose and UDP-N-acetylglucosamine transporter
name: SLC35B4
xref: UnificationXref11113
feature: FragmentFeature1872
cellular location: GO_0000139
comment: Reactome DB_ID: 5615162
display name: YEA4

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38317
data source: Provenance1
name: SLC33A1
name: ACATN_HUMAN
name: Acetyl-coenzyme A transporter 1
xref: UnificationXref11103
feature: FragmentFeature1871
cellular location: GO_0000139
comment: Reactome DB_ID: 5615145
display name: P38317

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38318
data source: Provenance1
name: SLC33A1
name: ACATN_HUMAN
name: Acetyl-coenzyme A transporter 1
xref: UnificationXref11101
feature: FragmentFeature1870
cellular location: GO_0000139
comment: Reactome DB_ID: 5615141
display name: P38318

Equilibrative transport (export) of nucleosides and adenine by solute carrier family 29 (nucleoside transporters), member 3
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1701
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11066
xref: UnificationXref11065
left: SmallMolecule1118
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1126

Evidence309
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16497588
xref: http://identifiers.org/pubmed/20237413
xref: http://identifiers.org/pubmed/15276183
xref: http://identifiers.org/pubmed/18652679
comment: Upon binding of their ligands, TLR7/8 and TLR9 recruit a cytoplasmic adaptor MyD88 and IRAKs, downstream of which the signaling pathways are divided to induce either inflammatory cytokines or type I IFNs.

Evidence308
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/22511786
xref: http://identifiers.org/pubmed/18794297
comment: TRAF6 mediates NFkB activation via canonical phosphorylation of IKK complex by TAK1. TRAF6 and TAK1 also regulate MAPK cascades leading to the activation of AP-1.

http://identifiers.org/pubmed/19006241
type: PublicationXref
id: 19006241
author: Häberle, J
author: Höhne, W
author: Engel, K
db: Pubmed
title: Mutations and polymorphisms in the human argininosuccinate synthetase (ASS1) gene
source: Hum Mutat 30:300-7
year: 2009

Evidence302
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9430229
xref: http://identifiers.org/pubmed/16239509
xref: http://identifiers.org/pubmed/10435584
xref: http://identifiers.org/pubmed/15728506
comment: Mammalian myeloid differentiation factor 88 (MyD88) is Toll/interleukin (IL)-1 (TIR)-domain containing adapter protein which plays crucial role in TLR signaling. All TLRs, with only one exception of TLR3, can initiate downstream signaling trough MyD88. In the MyD88 - dependent pathway, once the adaptor is bound to TLR it leads to recruitment of IL1 receptor associated kinase family IRAK which is followed by activation of tumour necrosis factor receptor-associated factor 6 (TRAF6) . TRAF6 is an ubiquitin E3 ligase which in turn induces TGF-beta activating kinase 1 (TAK1) auto phosphorylation. Once activated TAK1 can ultimately mediate the induction of the transcription factor NF-kB or the mitogen-activated protein kinases (MAPK), such as JNK, p38 and ERK. This results in the translocation of the activated NF-kB and MAPKs to the nucleus and the initiation of appropriate gene transcription leading to the production of many proinflammatory cytokines and antimicrobial peptides.

Evidence303
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18332149
xref: http://identifiers.org/pubmed/15728506
comment: Little is known about TLR10 ligands. It has been established that the receptor homodimerizes upon binding and signals in an MyD88-dependent manner (Hasan U et al 2005; Nyman T et al 2008). It may also heterodimerize with TLRs 1 and 2. It is expressed in a restricted fashion as a highly N-glycosylated protein detectable in B cells and dendritic cells.

Evidence300
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19092054
xref: http://identifiers.org/pubmed/19217269
xref: http://identifiers.org/pubmed/9316394
xref: http://identifiers.org/pubmed/8689559
xref: http://identifiers.org/pubmed/15531770
xref: http://identifiers.org/pubmed/15224094
xref: http://identifiers.org/pubmed/11684289
xref: http://identifiers.org/pubmed/19703008
comment: Antigen presenting cells (APCs) such as B cells, dendritic cells (DCs) and monocytes/macrophages express major histocompatibility complex class II molecules (MHC II) at their surface and present exogenous antigenic peptides to CD4+ T helper cells. CD4+ T cells play a central role in immune protection. On their activation they stimulate differentiation of B cells into antibody-producing B-cell blasts and initiate adaptive immune responses. MHC class II molecules are transmembrane glycoprotein heterodimers of alpha and beta subunits. Newly synthesized MHC II molecules present in the endoplasmic reticulum bind to a chaperone protein called invariant (Ii) chain. The binding of Ii prevents the premature binding of self antigens to the nascent MHC molecules in the ER and also guides MHC molecules to endocytic compartments. In the acidic endosomal environment, Ii is degraded in a stepwise manner, ultimately to free the class II peptide-binding groove for loading of antigenic peptides. Exogenous antigens are internalized by the APC by receptor mediated endocytosis, phagocytosis or pinocytosis into endocytic compartments of MHC class II positive cells, where engulfed antigens are degraded in a low pH environment by multiple acidic proteases, generating MHC class II epitopes. Antigenic peptides are then loaded into the class II ligand-binding groove. The resulting class II peptide complexes then move to the cell surface, where they are scanned by CD4+ T cells for specific recognition (Berger & Roche 2009, Zhou & Blum 2004, Watts 2004, Landsverk et al. 2009).

Evidence301
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/21682741
xref: http://identifiers.org/pubmed/11861602
xref: http://identifiers.org/pubmed/16551257
comment: Adaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with remarkable diversity tailored to recognize aspects of particular pathogens or antigens. During infection, dendritic cells (DC) which act as sentinels in the peripheral tissues recognize and pick up the pathogen in the form of antigenic determinants and then process these antigens and present them to T cells. These T cells of appropriate specificity respond to the antigen, and either kill the pathogen directly or secrete cytokines that will stimulate B lymphocyte response. B cells provide humoral immunity by secreting antibodies specific for the pathogen or antigen.

Evidence306
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15031527
xref: http://identifiers.org/pubmed/15733829
xref: http://identifiers.org/pubmed/18202435
xref: http://identifiers.org/pubmed/19627256
comment: Toll-like receptor 3 (TLR3) as was shown for mammals is expressed on myeloid dendritic cells, respiratory epithelium, macrophages, and appears to play a central role in mediating the antiviral and inflammatory responses of the innate immunity in combating viral infections. Mammalian TLR3 recognizes dsRNA, and that triggers the receptor to induce the activation of NF-kappaB and the production of type I interferons (IFNs). dsRNA-stimulated phosphorylation of two specific TLR3 tyrosine residues (Tyr759 and Tyr858) is essential for initiating TLR3 signaling pathways.

Evidence307
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11489966
xref: http://identifiers.org/pubmed/11323673
xref: PublicationXref739
comment: TLR5 is the receptor for flagellin, the protein that forms bacterial flagella. Unlike most other Pathogen-Associated Molecular Patterns (PAMPs), flagellin does not undergo any posttranslational modifications that would distinguish it from cellular proteins. However, flagellin is extremely conserved at its amino- and carboxyl-termini, which presumably explains why it was selected as a ligand for innate immune recognition. TLR5 is expressed on epithelial cells as well as on macrophages and dendritic cells. Expression of TLR5 on intestinal epithelium is polarized such that TLR5 is expressed only on the basolateral side of the cell, as pathogenic but not commensal microbes cross the epithelial barrier. This ensures that innate immune responses are confined to pathogenic but not commensal microbes (Paul 2004; Hayashi et al. 2001; Gewirtz et al. 2001).

Evidence304
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12855817
xref: http://identifiers.org/pubmed/14739303
xref: http://identifiers.org/pubmed/15814722
comment: TRIF(TICAM1) was shown to induce IRF3/7 and NF-?B activation and apoptosis through distinct intracellular signaling pathways [Han KJ et al 2004; Kaiser WJ and Offermann MK et al 2005]. TRIF consists of an N-terminal region (1-234), a TIR domain (235-500), and a C-terminal region (501-680). The N-terminal region of TRIF harbors TRAF (TNF receptor associated factor) family proteins and forms complexes containing IRF-3 and/or NFkB -activating kinases. The C-terminal region of TRIF can recruit receptor-interacting protein-1 (RIP-1), and this event is followed by the activation of IKK complex.

Evidence305
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/14556004
xref: http://identifiers.org/pubmed/15276183
xref: http://identifiers.org/pubmed/12539043
xref: http://identifiers.org/pubmed/18222170
xref: http://identifiers.org/pubmed/12855817
xref: http://identifiers.org/pubmed/18297073
comment: MyD88-independent signaling pathway is shared by TLR3 and TLR4 cascades. TIR-domain-containing adapter-inducing interferon-beta (TRIF or TICAM1) is a key adapter molecule in transducing signals from TLR3 and TLR4 in a MyD88-independent manner (Yamamoto M et al. 2003a). TRIF is recruited to ligand-stimulated TLR3 or 4 complex via its TIR domain. TLR3 directly binds TRIF (Oshiumi H et al 2003). In contrast, TLR4-mediated signaling pathway requires two adapter molecules, TRAM (TRIF-related adapter molecule or TICAM2) and TRIF. TRAM(TICAM2) is thought to bridge between the activated TLR4 complex and TRIF (Yamamoto M et al. 2003b, Tanimura N et al. 2008, Kagan LC et al. 2008). TRIF recruitment to TLR complex stimulates distinct pathways leading to production of type 1 interferons (IFNs), pro-inflammatory cytokines and induction of programmed cell death.

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P31381
data source: Provenance1
name: Equilibrative nucleoside transporter 4
name: SLC29A4
name: S29A4_HUMAN
xref: UnificationXref11091
feature: FragmentFeature1869
cellular location: GO_0005886
comment: Reactome DB_ID: 5615130
display name: P31381

UnificationXref8402
type: UnificationXref
id: 5616422
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616422

Homologues of SLC33A1
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref11104
cellular location: GO_0000139
comment: Reactome DB_ID: 5615146
comment: Converted from EntitySet in Reactome

NACT co-transports trivalent citrate and a sodium ion
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1686
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10915
xref: UnificationXref10914
left: SmallMolecule1047
left: SmallMolecule1078
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule400
right: SmallMolecule1046

UnificationXref8403
type: UnificationXref
id: REACT_180615
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_180615.3

UnificationXref8400
type: UnificationXref
id: REACT_125583
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_125583.1

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P31381
data source: Provenance1
name: SLC29A3
name: Equilibrative nucleoside transporter 3
name: S29A3_HUMAN
xref: UnificationXref11064
feature: FragmentFeature1868
cellular location: GO_0005765
comment: Reactome DB_ID: 5615135
display name: P31381

UnificationXref8401
type: UnificationXref
id: 5616350
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616350

ZnT1 mediates the efflux of zinc from the cell
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1690
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10982
xref: UnificationXref10983
left: SmallMolecule109
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1098

UnificationXref8406
type: UnificationXref
id: 5616394
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616394

ZIP7 mediates zinc efflux from the endoplasmic reticulum
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1692
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10990
xref: UnificationXref10991
left: SmallMolecule1099
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule109

UnificationXref8407
type: UnificationXref
id: REACT_181463
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_181463.3

MATEs mediate extrusion of xenobiotics
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1688
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10965
xref: UnificationXref10964
left: SmallMolecule1081
left: SmallMolecule1048
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule19
right: SmallMolecule1089

UnificationXref8404
type: UnificationXref
id: 1806195
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1806195

DCT1 (NRAMP2) mediates divalent iron uptake across the apical membrane of enterocytes
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1689
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10974
xref: UnificationXref10973
left: SmallMolecule1097
left: SmallMolecule1048
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule19
right: SmallMolecule239

UnificationXref8405
type: UnificationXref
id: REACT_125114
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_125114.1

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P0CD92
data source: Provenance1
name: Aquaporin-8
name: P0CD92
name: AQP8_HUMAN
xref: UnificationXref11149
feature: FragmentFeature1878
cellular location: GO_0005886
comment: Reactome DB_ID: 5614967
display name: AQP8

ABCD1/D2/D3 mediate long chain fatty acid transport in to peroxisomes
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1649
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10686
xref: UnificationXref10685
left: SmallMolecule1042
left: SmallMolecule15
left: SmallMolecule12
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1043
right: SmallMolecule54
right: SmallMolecule13

Homologues of AQP8
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
member physical entity: P0CD98
xref: UnificationXref11152
cellular location: GO_0005886
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5614974

CIA Targeting Complex transfers 4Fe-4S cluster to apoproteins
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1646
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10668
xref: UnificationXref10669
participant stoichiometry: Stoichiometry2282
participant stoichiometry: Stoichiometry2277
left: Protein2247
left: Complex863
left: Complex865
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Protein2241
right: Complex862
right: Complex865
right: Complex867

P0CD98
type: Protein
entity reference: P0CD98
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: Aquaporin-8
name: AQP8_HUMAN
xref: UnificationXref11151
feature: FragmentFeature1880
cellular location: GO_0005886
comment: Reactome DB_ID: 5614973
display name: AQP8

The ABCC family mediates organic anion transport
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1653
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10716
xref: UnificationXref10717
left: SmallMolecule15
left: SmallMolecule1044
left: SmallMolecule12
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule54
right: SmallMolecule13
right: SmallMolecule1045

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P0CD91
data source: Provenance1
name: Aquaporin-8
name: P0CD91
name: AQP8_HUMAN
xref: UnificationXref11150
feature: FragmentFeature1879
cellular location: GO_0005886
comment: Reactome DB_ID: 5614969
display name: AQP8

ABC7, mABC1 and mABC2 mediate heme transport
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1651
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10691
xref: UnificationXref10690
left: SmallMolecule964
left: SmallMolecule163
left: SmallMolecule31
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule117
right: SmallMolecule222
right: SmallMolecule25

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P23900
data source: Provenance1
name: Aquaporin-9
name: AQP9_HUMAN
name: P23900
xref: UnificationXref11154
feature: FragmentFeature1881
cellular location: GO_0005886
comment: Reactome DB_ID: 5614332
display name: AQP9

carbovir monophosphate + ATP => carbovir diphosphate + ADP
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1641
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10624
xref: UnificationXref10623
left: SmallMolecule1040
left: SmallMolecule12
display name: Phosphorylation of carbovir monophosphate
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1041
right: SmallMolecule13

Homologues of AQP9
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref11156
cellular location: GO_0005886
comment: Reactome DB_ID: 5614337
comment: Converted from EntitySet in Reactome

abacavir monophosphate + H2O => carbovir monophosphate + cyclopropylamine
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1640
conversion direction: LEFT_TO_RIGHT
EC number: 3.5.4.4
xref: UnificationXref10619
xref: UnificationXref10618
left: SmallMolecule15
left: SmallMolecule1038
display name: Deamination of abacavir monophosphate to form carbovir monophosphate
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1040
right: SmallMolecule1039

4Fe-4S cluster assembles on NUBP2:NUBP1 scaffold
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1645
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10650
xref: UnificationXref10649
participant stoichiometry: Stoichiometry2265
participant stoichiometry: Stoichiometry2266
participant stoichiometry: Stoichiometry2261
participant stoichiometry: Stoichiometry2262
left: SmallMolecule49
left: SmallMolecule50
left: Protein2241
left: Complex862
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex863

NADPH reduces NDOR1:CIAPIN1
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1644
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10638
xref: UnificationXref10639
left: SmallMolecule3
left: Complex857
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule6
right: SmallMolecule19
right: Complex860

UnificationXref11280
type: UnificationXref
id: REACT_105437
db: Reactome
id version: 4
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_105437.4

UnificationXref11281
type: UnificationXref
id: 5618037
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618037

UnificationXref11274
type: UnificationXref
id: 5617205
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617205

Evidence337
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10224668
xref: http://identifiers.org/pubmed/20400677
xref: PublicationXref842
comment: Phospholipases play an integral role in phagocytosis by generating essential second messengers. An early step in phagocytic signaling is the association of PIP2 and IP3 with the phagocytic cup. These are formed by the activity of phosphoinositol kinases and phospholipases. PI3K is has been shown to accumulate at phagocytic cups and converts PI (4,5)P2 to PI (3,4,5)P3. These phosphoinositides are capable of binding and increasing the activity of proteins that regulate the actin cytoskeleton. Phospholipases are lipid modifying enzymes that produce lipid mediators such as diacylglycerol (DAG), arachidonic acid (AA) and IP3. Phopsholipases PLA, PLC and PLD have been shown to be involved in antibody (IgG) mediated phagocytosis. The PLC product IP3 stimulates release of calcium from the endoplasmic reticulum. This Ca+2 concentration increase is greatest in the cytoplasm surrounding the phagocytic cup. Calcium is involved in the various stages of phagosome formation, including phagocytic ingestion and phagosome maturation.

UnificationXref11273
type: UnificationXref
id: 5617204
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617204

Evidence338
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12488490
xref: http://identifiers.org/pubmed/16413920
xref: http://identifiers.org/pubmed/8541526
xref: http://identifiers.org/pubmed/17050193
comment: Phagocytosis is one of the important innate immune responses that function to eliminate invading infectious agents. Monocytes, macrophages, and neutrophils are the professional phagocytic cells. Phagocytosis is a complex process involving the recognition of invading foreign particles by specific types of phagocytic receptors and the subsequent internalization of the particles. Fc gamma receptors (FCGRs) are among the best studied phagocytic receptors that bind to Fc portion of immunoglobulin G (IgG). Through their antigen binding F(ab) end, antibodies bind to specific antigen while their constant (Fc) region binds to FCGRs on phagocytes. The clustering of FCGRs by IgG antibodies on the phagocyte initiates a variety of signals, which lead, through the reorganisation of actin cytoskeleton and membrane remodelling, to the formation of pseudopod and phagosome. Fc gamma receptors are classified into three classes: FCGRI, FCGRII and FCGRIII. Each class of these FCGRs consists of several individual isoforms. Among all these isoforms FCGRI, FCGRIIA and FCGRIIIA, are able to mediate phagocytosis (Joshi et al. 2006, Garcia Garcia & Rosales 2002, Nimmerjahn & Ravetch 2006).

UnificationXref11272
type: UnificationXref
id: 5617203
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617203

Evidence339
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16407073
comment: The four protein kinase A (PKA) regulatory subunit isoforms differ in their tissue specificity and functional characteristics. The specific isoform activated in response to glucagon signalling is not known. The PKA kinase is a tetramer of two regulatory and two catalytic. The regulatory subunits block the catalytic subunits. Binding of cAMP to the regulatory subunit leads to the dissociation of the tetramer into two active dimers made up of a regulatory and a catalytic subunit.

UnificationXref11271
type: UnificationXref
id: REACT_161150
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_161150.1

UnificationXref11278
type: UnificationXref
id: REACT_204366
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_204366.2

Evidence333
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15452139
xref: http://identifiers.org/pubmed/15981459
xref: http://identifiers.org/pubmed/17477841
comment: The actin cytoskeleton is fundamental for phagocytosis and members of the Rho family GTPases RAC and CDC42 are involved in actin cytoskeletal regulation leading to pseudopod extension. Active RAC and CDC42 exert their action through the members of WASP family proteins (WASP/N-WASP/WAVE) and ARP2/3 complex. Actin filaments move from the bottom toward the top of the phagocytic cup during pseudopod extension.

UnificationXref11277
type: UnificationXref
id: 5618662
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618662

Evidence334
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Diacylglycerol (DAG) positively regulates the autophosphorylation of protein kinase C-delta (PKC-delta), which stimulates ERK1/2 and triggers neurite outgrowth. DAG also stimulates the translocation of PKC from the cytosol to the plasma membrane. PKC-delta contributes to growth factor specificity and response to neuronal cells by promoting cell-type-specific differences in growth factor signalling. DAG can also activate PKC-epsilon in the same manner.

UnificationXref11276
type: UnificationXref
id: REACT_221764
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_221764.2

Evidence335
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16497229
xref: http://identifiers.org/pubmed/10224668
xref: http://identifiers.org/pubmed/15294978
xref: http://identifiers.org/pubmed/9973503
comment: Phospholipase D (PLD) catalyses the hydrolysis of the membrane phospholipid, phosphatidylcholine (PC) to generate choline and metabolically active phosphatidic acid (PA) (Lennartz 1999). Pharmacological inhibition studies show that PLD participates in FCGR-mediated phagocytosis (Kusner et al. 1996). There is an increase in the activity of PLD following the activation of phagocytosis via FCGR (Kusner et al. 1999). Following activation of FCGR, PLD translocates to the plasma membrane at the phagocytic cup and generate PA. This PA can be converted to DAG through the action of phosphatidic acid phosphatase-1 (PAP-1). Thus activation of PLD may be an additional pathway leading to PKC activation. The two isoforms PLD1 and PLD2 are both shown to be essential for the formation of phagosome at different stages. PLD1 is localized on the endosomal/lysosomal compartment and PLD2 is localized at the plasma membrane. PLD2 may be linked to phagosome formation whereas PLD1 may be involved in the focal exocytosis at the plasma membrane and also in the maturation process (Carrotte et al. 2006).

UnificationXref11275
type: UnificationXref
id: 5617207
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5617207

Evidence336
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10224668
xref: http://identifiers.org/pubmed/17590538
comment: Phosphatidic acid phosphatase (PAP) bound to the plasma membrane catalyzes the dephosphorylation of phosphatidic acid (PA), yielding diacylglycerol (DAG) and inorganic phosphate. In humans, Diacylglycerol pyrophosphate (DPPL1 and DPPL2) perform this reaction.

Evidence330
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10219243
xref: http://identifiers.org/pubmed/9883880
xref: http://identifiers.org/pubmed/10995437
xref: http://identifiers.org/pubmed/19741094
xref: http://identifiers.org/pubmed/15452139
xref: http://identifiers.org/pubmed/10724160
comment: Wiskott-Aldrich syndrome protein (WASP) and Neural-WASP (N-WASP) proteins are scaffolds that transduce signals from cell surface receptors to the activation of the ARP2/3 complex and actin polymerization. WASP and N-WASP possess a central GTPase binding domain (GBD) and an NH2-terminal WASP homology domain 1 (WH1), adjacent to this is a basic region (B) and a C-terminal containing VCA region that contains: a V domain (verprolin homology/WASP homology 2), a C domain (connecting), and an A motif (acidic). The VCA region is responsible for binding to and activating the ARP2/3 complex (Bompard & Caron 2004, Callebaut et al 1998). Under resting conditions, WASP and N-WASP are maintained in an autoinhibition state via interaction of the N-terminal GBD and the C-terminal VCA domains. This prevents access of the ARP2/3 complex to the VCA region. Activated CDC42 binds to the GBD region in N-WASP and this interaction releases the VCA region from autoinhibition enabling binding of the ARP2/3 complex stimulating actin polymerization (Kim et al 2000, Park & Cox 2009). Phosphoinositides (PtdIns(4,5)P2) interact with the basic (B) region in WASP and this interaction is important for activation of the WASP and ARP2/3 complex.(Higgs & Pollard 2000).

Band 3 Anion Exchanger (AE1, SLC4A1) exchanges cytosolic chloride for extracellular bicarbonate
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1635
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10592
xref: UnificationXref10591
left: SmallMolecule1034
left: SmallMolecule1035
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule511
right: SmallMolecule1033

Evidence331
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12488490
xref: http://identifiers.org/pubmed/9705280
xref: http://identifiers.org/pubmed/12189515
xref: http://identifiers.org/pubmed/11804587
xref: http://identifiers.org/pubmed/10496324
xref: http://identifiers.org/pubmed/15548136
comment: PAK1, a downstream effector of CDC42 and RAC1, is found localized in phagosomes. Upon activation, PAK1 phosphorylates LIMK, which directly phosphorylates and inactivates cofilin, a protein that mediates depolymerization of actin filaments. Thus, RAC and CDC42 coordinate actin dynamics by inducing actin polymerization via ARP2/3 on one hand, and inhibiting actin depolyerization via LIMK and cofilin on the other (Garcia-Garcia & Rosales 2002). PAK1 exists as homodimer in a trans-inhibited conformation. The kinase inhibitory (KI) domain of one PAK1 molecule binds to the C-terminal catalytic domain of the other and inhibits catalytic activity. GTPases RAC1/CDC42 bind the GBD domain of PAK1 thereby altering the conformation of the KI domain, relieving inhibition of its catalytic domain, and allowing PAK1 autophosphorylation that is required for full kinase activity (Parrini et al. 2002, Zhao & Manser 2005).

UnificationXref11279
type: UnificationXref
id: 5618495
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618495

abacavir [cytosol] + ATP + H2O => abacavir[extracellular] + ADP + phosphate
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1638
conversion direction: LEFT_TO_RIGHT
EC number: 3.6.3.44
xref: UnificationXref10606
xref: UnificationXref10605
left: SmallMolecule15
left: SmallMolecule1036
left: SmallMolecule12
display name: ABCG2-mediated abacavir efflux
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule54
right: SmallMolecule1037
right: SmallMolecule13

Evidence332
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11804587
xref: http://identifiers.org/pubmed/11278486
comment: PAK1 needs autophosphorylation for complete activation. PAK1 is autophosphorylated at several sites, but S144 flanking the kinase inhibitor region and T423 within the catalytic domain are the two conserved sites that regulate the catalytic activity (Chong et al. 2001, Parrini et al. 2001).

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P43549
data source: Provenance1
name: Aquaporin-3
name: AQP3_HUMAN
name: P43549
xref: UnificationXref11142
feature: FragmentFeature1875
cellular location: GO_0005886
comment: Reactome DB_ID: 5614528
display name: AQP3

Homologues of AQP7
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref11147
cellular location: GO_0005886
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5614343

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P23900
data source: Provenance1
name: AQP7_HUMAN
name: Aquaporin-7
name: P23900
xref: UnificationXref11145
feature: FragmentFeature1876
cellular location: GO_0005886
comment: Reactome DB_ID: 5614341
display name: AQP7

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P43549
data source: Provenance1
name: AQP7_HUMAN
name: Aquaporin-7
name: P43549
xref: UnificationXref11146
feature: FragmentFeature1877
cellular location: GO_0005886
comment: Reactome DB_ID: 5614342
display name: AQP7

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P39524
data source: Provenance1
name: AT8A1_HUMAN
name: Probable phospholipid-transporting ATPase IA
name: P39524
xref: UnificationXref11233
feature: FragmentFeature1888
cellular location: GO_0005886
comment: Reactome DB_ID: 5615461
display name: ATP8A1

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P13586
data source: Provenance1
name: P13586
name: AT2C2_HUMAN
name: Calcium-transporting ATPase type 2C member 2
xref: UnificationXref11215
feature: FragmentFeature1887
cellular location: GO_0000139
comment: Reactome DB_ID: 5615445
display name: ATP2C2

SLC36A2-mediated uptake of glycine and proline
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1668
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10800
xref: UnificationXref10799
left: SmallMolecule1048
left: SmallMolecule1058
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule19
right: SmallMolecule1059

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P13586
data source: Provenance1
name: AT2C1_HUMAN
name: P13586
name: Calcium-transporting ATPase type 2C member 1
xref: UnificationXref11214
feature: FragmentFeature1886
cellular location: GO_0000139
comment: Reactome DB_ID: 5615444
display name: ATP2C1

SLC36A1-mediated uptake of glycine, proline, and alanine
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1667
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10794
xref: UnificationXref10793
left: SmallMolecule1048
left: SmallMolecule1056
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule19
right: SmallMolecule1057

ATP2C1/2
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref11216
cellular location: GO_0000139
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 5615446

Type III Na+/Pi cotransport
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1665
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10785
xref: UnificationXref10786
participant stoichiometry: Stoichiometry2292
participant stoichiometry: Stoichiometry2291
left: SmallMolecule1055
left: SmallMolecule1047
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule54
right: SmallMolecule1046

Group 2 - Cl-/HCO3- exchanger transport
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1663
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10775
xref: UnificationXref10776
left: SmallMolecule511
left: SmallMolecule1033
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1034
right: SmallMolecule1035

Na+/H+ exchanger transport (at late endosome membrane)
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1661
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10770
xref: UnificationXref10769
left: SmallMolecule1053
left: SmallMolecule1046
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1054
right: SmallMolecule19

Na+/H+ exchanger transport (at trans-golgi membrane)
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1660
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10761
xref: UnificationXref10762
left: SmallMolecule1051
left: SmallMolecule1046
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1052
right: SmallMolecule19

Homologues of ATP8B1
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref11238
cellular location: GO_0005886
comment: Reactome DB_ID: 5615470
comment: Converted from EntitySet in Reactome

Na+/H+ exchanger transport (at early endosome membrane)
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1659
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10754
xref: UnificationXref10755
left: SmallMolecule1049
left: SmallMolecule1046
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule19
right: SmallMolecule1050

UnificationXref11290
type: UnificationXref
id: 2167845
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2167845

UnificationXref11291
type: UnificationXref
id: REACT_161228
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_161228.1

http://identifiers.org/pubmed/22118461
type: PublicationXref
id: 22118461
author: Desai, Arshad
author: Hombauer, Hans
author: Smith, Catherine E
author: Campbell, Christopher S
author: Kolodner, Richard D
db: Pubmed
title: Visualization of eukaryotic DNA mismatch repair reveals distinct recognition and repair intermediates
source: Cell 147:1040-53
year: 2011

UnificationXref11292
type: UnificationXref
id: 2167831
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2167831

UnificationXref11283
type: UnificationXref
id: CHEBI:61473
db: ChEBI

Evidence328
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10399917
xref: http://identifiers.org/pubmed/10531386
xref: http://identifiers.org/pubmed/15173891
xref: http://identifiers.org/pubmed/16133426
xref: http://identifiers.org/pubmed/8672512
xref: http://identifiers.org/pubmed/7592757
xref: http://identifiers.org/pubmed/11723063
xref: http://identifiers.org/pubmed/8751438
comment: Advanced Glycosylation End- product-specific Receptor (AGER) also known as Receptor for Advanced Glycation End-products (RAGE) is a multi-ligand membrane receptor belonging to the immunoglobulin superfamily. It is considered to be a Pattern Recognition Receptor (Liliensiek et al. 2004). It recognizes a large variety of modified proteins known as advanced glycation/glycosylation endproducts (AGEs), a heterogenous group of structures that are generated by the Maillard reaction, a consequence of long-term incubation of proteins with glucose (Ikeda et al. 1996). Their accumulation is associated with diabetes, atherosclerosis, renal failure and ageing (Schmidt et al. 1999). The most prevalent class of AGE in vivo are N(6)-carboxymethyllysine (NECML) adducts (Kislinger et al. 1991). In addition to AGEs, AGER is a signal transduction receptor for amyloid-beta peptide (Ab) (Yan et al. 1996), mediating Ab neurotoxicity and promoting Ab influx into the brain. AGER also responds to the proinflammatory S100/calgranulins (Hofmann et al. 1999) and High mobility group protein B1 (HMGB1/Amphoterin/DEF), a protein linked to neurite outgrowth and cellular motility (Hori et al. 1995). The major inflammatory pathway stimulated by AGER activation is NFkappaB. Though the signaling cascade is unclear, several pieces of experimental data suggest that activation of AGER leads to sustained activation and upregulation of NFkappaB, measured as NFkappaB translocation to the nucleus, and increased levels of de novo synthesized NFkappaB (Bierhaus et al. 2001). As this is clearly an indirect effect it is represented here as positive regulation of NFkappaB translocation to the nucleus. AGER can bind ERK1/2 and thereby activate the MAPK and JNK cascades (Bierhaus et al. 2005).

UnificationXref11282
type: UnificationXref
id: REACT_233480
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_233480.1

Evidence329
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9799231
xref: http://identifiers.org/pubmed/15169870
xref: http://identifiers.org/pubmed/11950933
xref: http://identifiers.org/pubmed/19955216
comment: FCGR mediated phagocytosis requires CDC42 to stimulate actin polymerization, generating the force for phagocytic cup protrusion or pseudopod extension. CDC42 activation is restricted at the advancing edge of the phagocytic cup, where actin is concentrated, and is deactivated at the base of the phagocytic cup (Beemiller et al 2010). The mechanism behind the recruitment and activation of CDC42 during FCGR phagocytosis is unknown. VAV regulates the activation of RAC1 but not CDC42 and the GEF responsible for CDC42 activation during FCGR-mediated phagocytosis remains unidentified (Adam et al 2004, Patel et al 2002).

UnificationXref11285
type: UnificationXref
id: REACT_161538
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_161538.1

Evidence326
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17875812
xref: http://identifiers.org/pubmed/18446235
xref: http://identifiers.org/pubmed/21245903
xref: http://identifiers.org/pubmed/15967716
xref: http://identifiers.org/pubmed/12830145
xref: http://identifiers.org/pubmed/18928408
comment: The innate immune system is the first line of defense against invading microorganisms, a broad specificity response characterized by the recruitment and activation of phagocytes and the release of anti-bacterial peptides. The receptors involved recognize conserved molecules present in microbes called pathogen-associated molecular patterns (PAMPs), and/or molecules that are produced as a result of tissue injury, the damage associated molecular pattern molecules (DAMPs). PAMPs are essential to the pathogen and therefore unlikely to vary. Examples are lipopolysaccharide (LPS), peptidoglycans (PGNs) and viral RNA. DAMPs include intracellular proteins, such as heat-shock proteins and extracellular matrix proteins released by tissue injury, such as hyaluronan fragments. Non-protein DAMPs include ATP, uric acid, heparin sulfate and dsDNA. The receptors for these factors are referred to collectively as pathogen- or pattern-recognition receptors (PRRs). The best studied of these are the membrane-associated Toll-like receptor family. Less well studied but more numerous are the intracellular nucleotide-binding domain, leucine rich repeat containing receptors (NLRs) also called nucleotide binding oligomerization domain (NOD)-like receptors, a family with over 20 members in humans and over 30 in mice. These recognise PAMPs/DAMPs from phagocytosed microorganisms or from intracellular infections (Kobayashi et al. 2003, Proell et al. 2008, Wilmanski et al. 2008). Some NLRs are involved in process unrelated to pathogen detection such as tissue homeostasis, apoptosis, graft-versus-host disease and early development (Kufer & Sansonetti 2011). Structurally NLRs can be subdivided into the caspase-recruitment domain (CARD)-containing NLRCs (NODs) and the pyrin domain (PYD)-containing NLRPs (NALPs), plus outliers including ice protease (caspase-1) activating factor (IPAF) (Martinon & Tschopp, 2005). In practical terms, NLRs can be divided into the relatively well characterized NOD1/2 whic…

UnificationXref11284
type: UnificationXref
id: 2167821
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2167821

Evidence327
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8529130
xref: http://identifiers.org/pubmed/8855306
xref: http://identifiers.org/pubmed/1651976
xref: http://identifiers.org/pubmed/15289604
xref: http://identifiers.org/pubmed/10080935
comment: In addition to AGER/RAGE, several other proteins have been identified as AGE-binding proteins. AGE binding proteins p60 and p90 (Yang et al. 1991) were subsequently identified as the Oligosaccharyl transferase 48 kDa subunit (Ost-48) and Glucosidease-2 subunit beta (Li et al. 1996). A third member was identified as Galectin-3 (Vlassara et al. 1995). These 3 proteins have been shown to be present on the plasma membrane of many cell types including vascular endothelium (Stitt et al. 1999). They have been designated AGE-R1, -R2 and -R3. Their suggested function is the removal and degradation of AGEs, but AGER-1 was found to negatively regulate AGER/RAGE (Lu et al. 2004), with kinetics that suggested a more complex interaction than simple competition for the same ligand.

UnificationXref11287
type: UnificationXref
id: 2167846
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2167846

Evidence324
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/20303873
xref: http://identifiers.org/pubmed/15075209
xref: http://identifiers.org/pubmed/16498449
xref: http://identifiers.org/pubmed/11607846
xref: http://identifiers.org/pubmed/17036048
xref: http://identifiers.org/pubmed/18604214
xref: http://identifiers.org/pubmed/12766759
xref: http://identifiers.org/pubmed/19501527
comment: The NLRP3 (Cryopyrin) inflammasome is currently the best characterized. It consists of NLRP3, ASC (PYCARD) and procaspase-1; CARD8 (Cardinal) is also suggested to be a component. It is activated by a number of pathogens and bacterial toxins as well as diverse PAMPs, danger-associated molecular patterns (DAMPS) such as hyaluronan and uric acid, and exogenous irritants such as silica and asbestos (see Table S1 Schroder & Tschopp, 2010). Mutations in NLRP3 which lead to constitutive activation are linked to the human diseases Muckle-Wells syndrome, familial cold autoinflammatory syndrome and NOMID (Ting et al. 2006), characterized by skin rashes and other symptoms associated with generalized inflammation. The cause of these symptoms is uncontrolled IL-1 beta production. Multiple studies have shown that activation of the NLRP3 inflammasome by particulate activators (e.g. Hornung et al. 2008) requires phagocytosis, but this is not required for the response to ATP, which is mediated by the P2X7 receptor (Kahlenberg & Dubyak, 2004) and appears to involve the pannexin membrane channel (Pellegrin & Suprenenant 2006). Direct binding of activators to NLRP3 has not been demonstrated and the exact process of activation is unclear, though it is speculated to involve changes in conformation that free the NACHT domain for oligomerization (Inohara & Nunez 2001, 2003).

UnificationXref11286
type: UnificationXref
id: CHEBI:64253
db: ChEBI

Evidence325
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/20303873
xref: http://identifiers.org/pubmed/17186029
xref: http://identifiers.org/pubmed/15162420
xref: http://identifiers.org/pubmed/19302049
xref: http://identifiers.org/pubmed/19120480
xref: http://identifiers.org/pubmed/19120479
xref: http://identifiers.org/pubmed/12620239
xref: http://identifiers.org/pubmed/17164409
comment: In contrast to NOD1/2 some NLRPs function as large macromolecular complexes called 'Inflammasomes'. These multiprotein platforms control activation of the cysteinyl aspartate protease caspase-1 and thereby the subsequent cleavage of pro-interleukin 1B (pro-IL1B) into the active proinflammatory cytokine IL1B. Activation of caspase-1 is essential for production of IL1B and IL18, which respectively bind and activate the IL1 receptor (IL1R) and IL18 receptor (IL18R) complexes. IL1R and IL18R activate NFkappaB and other signaling cascades. As the activation of inflammasomes leads to caspase-1 activation, inflammasomes can be considered an upstream step of the IL1R and IL18R signaling cascades, linking intracellular pathogen sensing to immune response pathways mediated by Toll-Like Receptors (TLRs). Monocytes and macrophages do not express pro-IL1B until stimulated, typically by TLRs (Franchi et al. 2009). The resulting pro-IL1B is not converted to IL1B unless a second stimulus activates an inflammasome. This requirement for two distinct stimuli allows tight regulation of IL1B/IL18 production, necessary because excessive IL-1B production is associated with numerous inflammatory diseases such as gout and rheumatoid arthritis (Masters et al. 2009). There are at least four subtypes of the inflammasome, characterized by the NLRP. In addition the protein AIM2 can form an inflammasome. All activate caspase-1. NLRP1 (NALP1), NLRP3 (Cryopyrin, NALP3), IPAF (CARD12, NLRC4) and AIM2 inflammasomes all have clear physiological roles in vivo. NLRP2, NLRP6, NLRP7, NLRP10 and NLRP12 have been demonstrated to modulate caspase-1 activity in vitro but the significance of this is unclear (Mariathasan and Monack, 2007). NLRP3 and AIM2 bind the protein 'apoptosis-associated speck-like protein containing a CARD' (ASC, also called PYCARD), via a PYD-PYD domain interaction. This in turn recruits procaspase-1 through a CARD-CARD interaction. NLRP1 and IPAF contain CARD domains and can bind procas…

UnificationXref11289
type: UnificationXref
id: P41735
db: UniProt

Evidence322
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/14761955
comment: The ubiquitin ligaseâassociated protein SGT1 (SUGT1) has two putative HSP90 binding domains, a tetratricopeptide repeat and a p23-like CHORD and Sgt1 (CS) domain. The CS domain of human SGT1 physically interacts with HSP90. SGT1 and related proteins are believed to recruit heat shock proteins to multiprotein assemblies (Lee et al. 2004).

UnificationXref11288
type: UnificationXref
id: REACT_161451
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_161451.1

Evidence323
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17132626
xref: http://identifiers.org/pubmed/18403674
xref: http://identifiers.org/pubmed/20023662
comment: The presence of reactive oxygen species (ROS) leads to the oxidation of thioredoxin and consequent release of TXNIP (Zhou et al. 2010). The source of the ROS is unclear but they are known to be essential for caspase-1 activation (Cruz et al. 2007) and are produced in response to all known NLRP3 activators (Dostert et al. 2008, Zhou et al. 2010). The freed TXNIP binds NLRP3 and is proposed to activate the NLRP3 inflammasome, explaining how ROS can bring about NLRP3 activation.

Na+-coupled HCO3- cotransport
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1656
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10736
xref: UnificationXref10735
participant stoichiometry: Stoichiometry2290
participant stoichiometry: Stoichiometry2289
left: SmallMolecule511
left: SmallMolecule1046
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1035
right: SmallMolecule1047

Evidence320
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8633070
xref: http://identifiers.org/pubmed/8663524
xref: http://identifiers.org/pubmed/15686620
xref: http://identifiers.org/pubmed/9430721
xref: http://identifiers.org/pubmed/10066767
xref: http://identifiers.org/pubmed/7693711
comment: p38 MAPK has 4 representative isoforms in humans, p38 alpha (Han et al. 1993), p38-beta (Jiang et al. 1996), p38-gamma (Lechner et al. 1996) and p38-delta (Hu et al. 1999). All are activated by phosphorylation on a canonical TxY motif by the dual-specificity kinase MKK6, which displays minimal substrate selectivity amongst the p38 isoforms (Zarubin & Han, 2005). p38 alpha and gamma are also activated by MKK3.

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P43549
data source: Provenance1
name: Aquaporin-9
name: P43549
name: AQP9_HUMAN
xref: UnificationXref11155
feature: FragmentFeature1882
cellular location: GO_0005886
comment: Reactome DB_ID: 5614336
display name: AQP9

Na+-driven Cl-/HCO3- exchanger transport
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1657
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10742
xref: UnificationXref10743
left: SmallMolecule19
left: SmallMolecule1034
left: SmallMolecule1035
left: SmallMolecule1047
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule511
right: SmallMolecule1033
right: SmallMolecule1048
right: SmallMolecule1046

Evidence321
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18079694
xref: http://identifiers.org/pubmed/17348859
xref: http://identifiers.org/pubmed/18414735
xref: http://identifiers.org/pubmed/18585455
xref: http://identifiers.org/pubmed/18928408
xref: http://identifiers.org/pubmed/18342009
xref: http://identifiers.org/pubmed/15952891
comment: NOD1 is ubiquitously expressed, while NOD2 expression is restricted to monocytes, macrophages, dendritic cells, and intestinal Paneth cells (Inohara et al. 2005). NOD1 and NOD2 activation induces transcription of immune response genes, predominantly mediated by the proinflammatory transcriptional factor NFkappaB but also by AP-1 and Elk-1 (Inohara et al. 2005). NFkappaB translocates to the nucleus following release from IkappaB proteins. NOD1 and NOD2 signaling involves an interaction between their caspase-recruitment domain (CARD) and the CARD of the kinase RIPK2 (RIP2/RICK). This leads to the activation of the NFkappaB pathway and MAPK pathways (Windheim et al. 2007). Activated NODs oligomerize via their NACHT domains, inducing physical proximity of RIP2 proteins that is believed to trigger their K63-linked polyubiquitination, facilitating recruitment of the TAK1 complex. RIP2 also recruits NEMO, bringing the TAK1 and IKK complexes into proximity, leading to NF-kappaB activation and activation of MAPK signaling. Recent studies have demonstrated that K63-linked regulatory ubiquitination of RIP2 is essential for the recruitment of TAK1 (Hasegawa et al. 2008, Hitosumatsu et al. 2008). As observed for toll-like receptor (TLR) signaling, ubiquitination can be removed by the deubiquitinating enzyme A20, thereby dampening NOD1/NOD2-induced NF-kappaB activation. NOD1 and NOD2 both induce K63-linked ubiquitination of RIP2, but NOD2-signaling appears to preferentially utilize the E3 ligase TRAF6, while TRAF2 and TRAF5 were shown to be important for NOD1-mediated signaling. In both cases, activation of NF-kappaB results in the upregulated transcription and production of inflammatory mediators.

Cl-/HCO3- exchanger transport
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1655
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref10724
xref: UnificationXref10723
left: SmallMolecule511
left: SmallMolecule1033
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: SmallMolecule1034
right: SmallMolecule1035

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P43549
data source: Provenance1
name: Aquaporin-10
name: AQP10_HUMAN
name: P43549
xref: UnificationXref11159
feature: FragmentFeature1884
cellular location: GO_0005886
comment: Reactome DB_ID: 5614977
display name: AQP10

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P38995
data source: Provenance1
name: Copper-transporting ATPase 2
name: P38995
name: ATP7B_HUMAN
xref: UnificationXref11208
feature: FragmentFeature1885
cellular location: GO_0000139
comment: Reactome DB_ID: 5615453
display name: ATP7B

Homologues of AQP10
type: Protein
data source: Provenance1
member physical entity: Note: the coordinates are copied over from Homo sapiens.
xref: UnificationXref11160
cellular location: GO_0005886
comment: Reactome DB_ID: 5614978
comment: Converted from EntitySet in Reactome

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P23900
data source: Provenance1
name: Aquaporin-10
name: AQP10_HUMAN
name: P23900
xref: UnificationXref11158
feature: FragmentFeature1883
cellular location: GO_0005886
comment: Reactome DB_ID: 5614976
display name: AQP10

Evidence341
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: When cAMP level rises, the PKA catalytic subunit (C subunit) released from the holoenzyme enters the nucleus by passive diffusion whereas termination of signaling to the nucleus involves an active mechanism. In the nucleus, the C subunit binds to the heat-stable protein kinase inhibitor (PKI), and this binding not only inactivates the C subunit but also by conformational change unveils a nuclear export signal in PKI which leads to export of the C-PKI complex from the nucleus.

UnificationXref279
type: UnificationXref
id: P28743
db: UniProt

Evidence340
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/2165385
comment: A number of inactive tetrameric PKA holoenzymes are produced by the combination of homo- or heterodimers of the different regulatory subunits associated with two catalytic subunits. When cAMP binds to two specific binding sites on the regulatory subunits, these undergo a conformational change that causes the dissociation of a dimer of regulatory subunits bound to four cAMP from two monomeric, catalytically active PKA subunits.

3' incision of the lesioned strand of DNA in TC-NER
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1819
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11641
xref: UnificationXref11640
left: PhysicalEntity172
left: Complex920
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: PhysicalEntity173
right: Complex920

Evidence343
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11042191
comment: GRK2 is phosphorylated at serine 29 in vitro and in vivo by the alpha, gamma and delta isoforms of PKC. PKC-mediated phosphorylation at Ser29 increases GRK2 kinase activity towards GPCR substrates, contributing to GPCR desensitization. Phosphorylation at Ser29, which falls within the calmodulin-binding region of GRK2, abolishes the inhibitory effect of calmodulin on GRK2 kinase activity.

Displacement of stalled Pol II from the lesion site
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1818
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11637
xref: UnificationXref11636
left: Complex919
left: Complex920
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex921
right: PhysicalEntity172
right: Complex920

Evidence342
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16125054
xref: http://identifiers.org/pubmed/15337521
comment: Cyclic adenosine 3',5'-monophosphate (cAMP) induces gene transcription through activation of cAMP-dependent protein kinase (PKA), and subsequent phosphorylation of the transcription factor cAMP response element-binding protein, CREB, at serine-133.

http://identifiers.org/pubmed/16413920
type: PublicationXref
id: 16413920
author: Nimmerjahn, F
author: Ravetch, JV
db: Pubmed
title: Fcgamma receptors: old friends and new family members
source: Immunity 24:19-28
year: 2006

YDC1
type: ProteinReference
name: UniProt:Q02896
xref: UnificationXref8659
organism: http://identifiers.org/taxonomy/4932

Evidence349
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19290926
xref: http://identifiers.org/pubmed/17122878
xref: http://identifiers.org/pubmed/19909365
xref: http://identifiers.org/pubmed/16470226
xref: http://identifiers.org/pubmed/17420272
comment: Formation of the LAT signaling complex leads to activation of MAPK and production of cytokines. The sequence of events that leads from LAT to cytokine production has not been as clearly defined as the sequence that leads to degranulation. However, the pathways that lead to cytokine production require the guanine-nucleotide-exchange factors SOS and VAV that regulate GDP-GTP exchange of RAS. After its activation, RAS positively regulates the RAF-dependent pathway that leads to phosphorylation and, in part, activation of the mitogen-activated protein kinases (MAPKs) extracellular-signal-regulated kinase 1 (ERK1) and ERK2 (Gilfillan & Tkaczyk 2006).

UnificationXref271
type: UnificationXref
id: P28742
db: UniProt

UnificationXref1257
type: UnificationXref
id: 2564810
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564810

Evidence348
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9490415
xref: http://identifiers.org/pubmed/18192027
xref: http://identifiers.org/pubmed/15884055
xref: http://identifiers.org/pubmed/17220916
xref: http://identifiers.org/pubmed/19120482
comment: DNAX activation protein of 12kDa (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapter molecule that transduces activating signals in natural killer (NK) and myeloid cells. It mediates signalling for multiple cell-surface receptors expressed by these cells, associating with receptor chains through complementary charged transmembrane amino acids that form a salt-bridge in the context of the hydrophobic lipid bilayer (Lanier et al. 1998). DAP12 homodimers associate with a variety of receptors expressed by macrophages, monocytes and myeloid cells including TREM2, Siglec H and SIRP-beta, as well as activating KIR, LY49 and the NKG2C proteins expressed by NK cells. DAP12 is expressed at the cell surface, with most of the protein lying on the cytoplasmic side of the membrane (Turnbull & Colonna 2007, Tessarz & Cerwenka 2008).

UnificationXref272
type: UnificationXref
id: 5615601
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615601

UnificationXref1256
type: UnificationXref
id: REACT_160729
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160729.1

UnificationXref273
type: UnificationXref
id: P27895
db: UniProt

UnificationXref1255
type: UnificationXref
id: 2564762
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564762

UnificationXref274
type: UnificationXref
id: 5615605
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615605

UnificationXref1254
type: UnificationXref
id: P52920
db: UniProt

Evidence345
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10884684
comment: Calmodulin (CaM) is a small acidic protein that contains four EF-hand motifs, each of which can bind a calcium ion, therefore it can bind up to four calcium ions. The protein has two approximately symmetrical domains, separated by a flexible hinge region. Calmodulin is the prototypical example of the EF-hand family of Ca2+-sensing proteins. Changes in intracellular Ca2+ concentration regulate calmodulin in three distinct ways. First, by directing its subcellular distribution. Second, by promoting association with different target proteins. Third, by directing a variety of conformational states in calmodulin that result in target-specific activation. Calmodulin binds and activates several effector protein (e.g. the CaM-dependent adenylyl cyclases, phosphodiesterases, protein kinases and the protein phosphatase calcineurin).

UnificationXref275
type: UnificationXref
id: 5615606
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615606

UnificationXref1253
type: UnificationXref
id: REACT_160474
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160474.1

ASN2
type: ProteinReference
name: UniProt:P49090
xref: UnificationXref5329
organism: http://identifiers.org/taxonomy/4932

Evidence344
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15381755
comment: One important physiological role for Calmodulin is the regulation of adenylylcyclases. Four of the nine known adenylylcyclases are calcium sensitive, in particular type 8 (AC8).

UnificationXref276
type: UnificationXref
id: 5615607
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615607

UnificationXref1252
type: UnificationXref
id: 2564764
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564764

Evidence347
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17110943
xref: http://identifiers.org/pubmed/15884055
xref: http://identifiers.org/pubmed/17220916
comment: In response to receptor ligation, the tyrosine residues in DAP12's immunoreceptor tyrosine-based activation motif (ITAM) are phosphorylated by Src family kinases. These phosphotyrosines form the docking site for the protein tyrosine kinase SYK in myeloid cells and SYK and ZAP70 in NK cells. DAP12-bound SYK autophosphorylates and phosphorylates the scaffolding molecule LAT, recruiting the proximal signaling molecules phosphatidylinositol-3-OH kinase (PI3K), phospholipase-C gamma (PLC-gamma), GADS (GRB2-related adapter downstream of SHC), SLP76 (SH2 domain-containing leukocyte protein of 76 kDa), GRB2:SOS (Growth factor receptor-bound protein 2:Son of sevenless homolog 1) and VAV. All of these intermediate signalling molecules result in the recruitment and activation of kinases AKT, CBL (Casitas B-lineage lymphoma) and ERK (extracellular signal-regulated kinase), and rearrangement of the actin cytoskeleton (actin polymerization) finally leading to cellular activation. PLC-gamma generates the secondary messengers diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (InsP3), leading to activation of protein kinase C (PKC) and calcium mobilization, respectively (Turnbull & Colonna 2007, Klesney-Tait et al. 2006).

UnificationXref277
type: UnificationXref
id: 5615608
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615608

UnificationXref1251
type: UnificationXref
id: P40558
db: UniProt

Evidence346
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16260143
comment: This pathway describes the generation of DAG and IP3 by the PLCgamma-mediated hydrolysis of PIP2 and the subsequent downstream signaling events.

UnificationXref278
type: UnificationXref
id: REACT_263261
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_263261.1

UnificationXref1250
type: UnificationXref
id: REACT_5741
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5741.2

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: UniProt:P14242
data source: Provenance1
name: PMS2_HUMAN
name: P14242
name: Mismatch repair endonuclease PMS2 ecNumber3.1.-.-/ecNumber
xref: UnificationXref11678
feature: FragmentFeature1937
cellular location: GO_0005654
comment: Reactome DB_ID: 5617934
display name: PMS2

P38920
type: Protein
entity reference: P38920
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: MLH1_HUMAN
name: DNA mismatch repair protein Mlh1
xref: UnificationXref11680
feature: FragmentFeature1938
cellular location: GO_0005654
comment: Reactome DB_ID: 5617930
display name: MLH1

UnificationXref281
type: UnificationXref
id: 5615619
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615619

UnificationXref1258
type: UnificationXref
id: REACT_160746
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160746.1

AAC3
type: ProteinReference
name: UniProt:P18238
xref: UnificationXref8825
organism: http://identifiers.org/taxonomy/4932

UnificationXref280
type: UnificationXref
id: 5615618
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615618

UnificationXref1259
type: UnificationXref
id: 2564803
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564803

PET9
type: ProteinReference
name: UniProt:P18239
xref: UnificationXref8822
organism: http://identifiers.org/taxonomy/4932

MSH2:MSH6 exchanges ADP for ATP
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1828
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11675
xref: UnificationXref11676
participant stoichiometry: Stoichiometry2424
participant stoichiometry: Stoichiometry2430
left: SmallMolecule36
left: Complex924
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex925
right: SmallMolecule37

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P06777
data source: Provenance1
name: P06777
name: XPF protein
name: DNA excision repair protein ERCC-4
name: DNA-repair protein complementing XP-F cell
name: DNA-repair protein complementing XP-F cell (Xeroderma pigmentosum group F complementing protein) (DNA excision repair protein ERCC-4)
name: Xeroderma pigmentosum group F complementing protein
xref: UnificationXref11585
feature: FragmentFeature1929
cellular location: GO_0005654
comment: Reactome DB_ID: 5610171
display name: ERCC4

MSH2:MSH6 recruits MLH1:PMS2 to mismatch and interacts with PCNA
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1829
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11683
xref: UnificationXref11684
left: Complex927
left: Complex925
left: Complex98
display name: MutSalpha binds ATP and recruits MutLalpha to mismatch
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex928

phospho-p-S2,S5-POLR2A
type: Protein
entity reference: P04050
data source: Provenance1
xref: UnificationXref11613
feature: ModificationFeature210
feature: ModificationFeature342
feature: FragmentFeature1930
cellular location: GO_0005654
comment: Reactome DB_ID: 5610902

MLH1:PMS2 makes single strand incision near 1-2 base mismatch
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1830
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11688
xref: UnificationXref11689
left: Complex928
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex929

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: Q04048
data source: Provenance1
name: HCNP protein
name: Q04048
name: PP3898
name: XPA-binding protein 2
xref: UnificationXref11623
feature: FragmentFeature1931
cellular location: GO_0005654
comment: Reactome DB_ID: 5610913
display name: XAB2

EXO1 interacts with MSH2:MSH6 (MutSalpha) and MLH1:PMS2 (MutLalpha)
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1831
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11693
xref: UnificationXref11694
left: Exonuclease 1
left: Complex929
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex930

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P40352
data source: Provenance1
name: P40352
name: DNA excision repair protein ERCC-6
name: Cockayne syndrome protein CSB
name: Excision repair protein ERCC-6 (Cockayne syndrome protein CSB)
name: CSB protein
xref: UnificationXref11625
feature: FragmentFeature1932
cellular location: GO_0005654
comment: Reactome DB_ID: 5610921
display name: ERCC6

5' incision leading to excision of DNA fragment with lesion in TC-NER
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1820
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11647
xref: UnificationXref11646
left: PhysicalEntity173
left: Complex920
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: PhysicalEntity174
right: PhysicalEntity175
right: Complex920

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P07273
data source: Provenance1
name: Transcription elongation factor TFIIS.o
name: TFIIS protein
name: Transcription elongation factor A protein 1 (Transcription elongation factor S-II protein 1) (Transcription elongation factor TFIIS.o)
name: Transcription elongation factor A protein 1
name: P07273
name: Transcription elongation factor S-II protein 1
xref: UnificationXref11627
feature: FragmentFeature1933
cellular location: GO_0005654
comment: Reactome DB_ID: 5610909
display name: TCEA1

http://identifiers.org/pubmed/11779870
type: PublicationXref
id: 11779870
author: Tsurumi, T
author: Fujita, M
author: Kiyono, T
author: Nakamura, H
author: Ishimi, Y
db: Pubmed
title: Nuclear organization of DNA replication initiation proteins in mammalian cells.
source: J Biol Chem 277:10354-61
year: 2002

Ligation of newly synthesized repair patch to incised DNA in TC-NER
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1822
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11653
xref: UnificationXref11652
left: PhysicalEntity174
left: PhysicalEntity169
left: Protein597
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: PhysicalEntity176
right: Protein597

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: Q12021
data source: Provenance1
name: DNA excision repair protein ERCC-8
name: Cockayne syndrome WD-repeat protein CSA
name: Q12021
name: CSA protein
xref: UnificationXref11629
feature: FragmentFeature1934
cellular location: GO_0005654
comment: Reactome DB_ID: 5610917
display name: ERCC8

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P25847
data source: Provenance1
name: P25847
name: DNA mismatch repair protein Msh2
name: MSH2_HUMAN
xref: UnificationXref11666
feature: FragmentFeature1935
cellular location: GO_0005654
comment: Reactome DB_ID: 5617939
display name: MSH2

Resumption of transcription after TC-NER
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1824
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11658
xref: UnificationXref11657
left: PhysicalEntity176
left: Complex921
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex922

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: Q03834
data source: Provenance1
name: Q03834
name: DNA mismatch repair protein Msh6
name: MSH6_HUMAN
xref: UnificationXref11668
feature: FragmentFeature1936
cellular location: GO_0005654
comment: Reactome DB_ID: 5617943
display name: MSH6

MSH2:MSH6 binds 1 base mismatch or 1-2 base insertion/deletion loop
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1827
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11671
xref: UnificationXref11672
left: PhysicalEntity177
left: Complex923
display name: MutSalpha binds mismatch or 1-2 base insertion/deletion loop
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex924

http://identifiers.org/pubmed/12205100
type: PublicationXref
id: 12205100
author: Van Komen, S
author: Sigurdsson, S
author: Petukhova, G
author: Sung, P
db: Pubmed
title: Homologous DNA pairing by human recombination factors Rad51 and Rad54
source: J Biol Chem 277:42790-4
year: 2002

XPC binds to HR23B forming a heterodimeric complex
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1802
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11560
xref: UnificationXref11561
left: Note: the coordinates are copied over from Homo sapiens.
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex910

Evidence354
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Innate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup

Evidence353
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11449275
xref: http://identifiers.org/pubmed/22112783
xref: http://identifiers.org/pubmed/15099567
xref: http://identifiers.org/pubmed/9354811
xref: http://identifiers.org/pubmed/21799019
xref: http://identifiers.org/pubmed/14630197
comment: Mast cells (MC) are distributed in tissues throughout the human body and have long been recognized as key cells of type I hypersensitivity reactions. They also play important roles in inflammatory and immediate allergic reactions. Activation through FCERI-bound antigen-specific IgE causes release of potent inflammatory mediators, such as histamine, proteases, chemotactic factors, cytokines and metabolites of arachidonic acid that act on the vasculature, smooth muscle, connective tissue, mucous glands and inflammatory cells (Borish & Joseph 1992, Amin 2012, Metcalfe et al. 1993). FCERI is a multimeric cell-surface receptor that binds the Fc fragment of IgE with high affinity. On mast cells and basophils FCERI exists as a tetrameric complex consisting of one alpha-chain, one beta-chain, and two disulfide-bonded gamma-chains, and on dendritic cells, Langerhans cells, macrophages, and eosinophils it exists as a trimeric complex with one alpha-chain and two disulfide-bonded gamma-chains (Wu 2011, Kraft & Kinet 2007). FCERI signaling in mast cells includes a network of signaling molecules and adaptor proteins. These molecules coordinate ultimately leading to effects on degranulation, eicosanoid production, and cytokine and chemokine production and cell migration and adhesion, growth and survival. The first step in FCERI signaling is the phosphorylation of the tyrosine residues in the ITAM of both the beta and the gamma subunits of the FCERI by LYN, which is bound to the FCERI beta-chain. The phosphorylated ITAM then recruits the protein tyrosine kinase SYK (spleen tyrosine kinase) which then phosphorylates the adaptor protein LAT. Phosphorylated LAT (linker for activation of T cells) acts as a scaffolding protein and recruits other cytosolic adaptor molecules GRB2 (growth-factor-receptor-bound protein 2), GADS (GRB2-related adaptor protein), SHC (SRC homology 2 (SH2)-domain-containing transforming protein C) and SLP76 (SH2-domain-containing leukocyte protein of 76 kDa), a…

Evidence352
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17911602
xref: http://identifiers.org/pubmed/15477348
xref: http://identifiers.org/pubmed/15477350
xref: http://identifiers.org/pubmed/17993265
xref: http://identifiers.org/pubmed/20643813
xref: http://identifiers.org/pubmed/17420272
comment: The lipid raft resident adaptor molecules LAT1 and Non-T cell activation linker (NTAL), also known as linker for activation of B cells (LAB)/LAT2 are known participants in the regulation of mast cell calcium responses. Both LAT and NTAL are expressed and phosphorylated following engagement of FCERI on mast cells. NTAL is functionally and topographically different from LAT. There is a considerable debate on the role of NTAL in mast cell. Depending on the circumstances, NTAL appears to have a dual role as positive and negative regulator of MC responses elicited via FCERI. Studies conducted in bone marrow-derived mast cells (BMMCs) of mice lacking NTAL displayed enhanced FCERI-mediated tyrosine phosphorylation of several substrates, calcium response, degranulation, and cytokine production. This indicated that NTAL negatively regulates FCERI-mediated degranulation. However, in mice lacking both LAT and NTAL showed severe block in FCERI-mediated signaling than BMMCs deficient in LAT alone, suggesting that NTAL also shares a redundant function with LAT to play a positive role (Draberova et al. 2007, Orr & McVicar. 2011, Zhu et al. 2004, Volna et al. 2004). The major steps in NTAL mediated Ca+2 influx involves NTAL--> GAB2--> PI3K

UnificationXref268
type: UnificationXref
id: 5615654
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615654

Evidence351
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17336609
xref: http://identifiers.org/pubmed/17182539
xref: http://identifiers.org/pubmed/16432253
comment: The increase in intracellular Ca+2 in conjunction with DAG also activates PKC and RasGRP, which inturn contributes to cytokine production by mast cells (Kambayashi et al. 2007). Activation of the FCERI engages CARMA1, BCL10 and MALT1 complex to activate NF-kB through PKC-theta (Klemm et al. 2006, Chen et al. 2007). FCERI stimulation leads to phosphorylation, and degradation of IkB which allows the release and nuclear translocation of the NF-kB proteins. Activation of the NF-kB transcription factors then results in the synthesis of several cytokines. NF-kB activation by FCERI is critical for proinflammatory cytokine production during mast cell activation and is crucial for allergic inflammatory diseases (Klemm et al. 2006).

UnificationXref269
type: UnificationXref
id: 5615655
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615655

http://identifiers.org/pubmed/9564029
type: PublicationXref
id: 9564029
author: Kushner, JP
author: Phillips, JD
author: Hill, CP
author: Whitby, FG
db: Pubmed
title: Crystal structure of human uroporphyrinogen decarboxylase
source: EMBO J 17:2463-71
year: 1998

http://identifiers.org/pubmed/3413114
type: PublicationXref
id: 3413114
author: Cram, LS
author: Wu, JR
author: Ratliff, RL
author: Buckingham, JM
author: Moyzis, RK
author: Jones, MD
author: Meyne, J
author: Deaven, LL
author: Dani, M
db: Pubmed
title: A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes
source: Proc Natl Acad Sci U S A 85:6622-6
year: 1988

Evidence350
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11772397
xref: http://identifiers.org/pubmed/16252004
xref: http://identifiers.org/pubmed/22798961
comment: T219, T538 at the activation loop, S676 at the turn motif and S695 at the hydrophobic motif are autophosphorylated in cis-maanner. Posphorylation of T538 is critical for kinase activation and it stabilises the open active conformation. Some studies suggest the involvement of PDK1 (3-phosphoinositide-dependent protein kinase 1) and GLK kinases in the phosphorylation T538.

UnificationXref262
type: UnificationXref
id: REACT_262174
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_262174.1

UnificationXref1244
type: UnificationXref
id: REACT_160264
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160264.3

http://identifiers.org/pubmed/8428594
type: PublicationXref
id: 8428594
author: Marcote, MJ
author: Clarke, PR
author: Draetta, G
author: Karsenti, E
author: Hoffmann, I
db: Pubmed
title: Phosphorylation and activation of human cdc25-C by cdc2--cyclin B and its involvement in the self-amplification of MPF at mitosis
source: EMBO J 12:53-63
year: 1993

UnificationXref263
type: UnificationXref
id: Q06409
db: UniProt

UnificationXref1243
type: UnificationXref
id: 2564819
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564819

UnificationXref260
type: UnificationXref
id: 5615673
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615673

UnificationXref1246
type: UnificationXref
id: 2566513
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2566513

http://identifiers.org/pubmed/4218100
type: PublicationXref
id: 4218100
author: Matalon, R
author: Brandt, IK
author: Dorfman, A
author: Justice, P
author: Arbogast, B
db: Pubmed
title: Morquio's syndrome: deficiency of a chondroitin sulfate N-acetylhexosamine sulfate sulfatase
source: Biochem Biophys Res Commun 61:759-65
year: 1974

http://identifiers.org/pubmed/11130078
type: PublicationXref
id: 11130078
author: Sato, S
author: Takeda, K
author: Wagner, H
author: Sanjo, H
author: Takeuchi, O
author: Hoshino, K
author: Matsumoto, M
author: Kaisho, T
author: Kawai, T
author: Hemmi, H
author: Akira, S
db: Pubmed
title: A Toll-like receptor recognizes bacterial DNA
source: Nature 408:740-5
year: 2000

Evidence359
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/1501243
comment: Activated epidermal growth factor receptors (EGFR) can stimulate phosphatidylinositol (PI) turnover. Activated EGFR can activate phospholipase C-gamma1 (PLC-gamma1, i.e. PLCG1) which hydrolyses phosphatidylinositol 4,5-bisphosphate (PIP2) to inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). IP3 is instrumental in the release of calcium from intracellular stores and DAG is involved in protein kinase C activation.

UnificationXref261
type: UnificationXref
id: 5615674
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615674

UnificationXref1245
type: UnificationXref
id: CHEBI:26833
db: ChEBI

Evidence358
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Humans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first critical hours and days of exposure to a new pathogen, our innate immune system.

UnificationXref266
type: UnificationXref
id: P19073
db: UniProt

UnificationXref1240
type: UnificationXref
id: REACT_160350
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160350.1

Evidence357
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: PublicationXref897
xref: PublicationXref896
xref: PublicationXref895
xref: http://identifiers.org/pubmed/12613569
comment: Cytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concentrations. Cytokines bind to specific membrane receptors, which then signal the cell via second messengers, to regulate cellular activity.

UnificationXref267
type: UnificationXref
id: 5612311
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5612311

Evidence356
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19302047
xref: http://identifiers.org/pubmed/12445398
comment: Interleukins are low molecular weight proteins that bind to cell surface receptors and act in an autocrine and/or paracrine fashion. They were first identified as factors produced by leukocytes but are now known to be produced by many other cells throughout the body. They have pleiotropic effects on cells which bind them, impacting processes such as tissue growth and repair, hematopoietic homeostasis, and multiple levels of the host defense against pathogens where they are an essential part of the immune system.

UnificationXref264
type: UnificationXref
id: 5615652
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615652

UnificationXref1242
type: UnificationXref
id: REACT_161421
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_161421.1

Evidence355
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12525482
xref: http://identifiers.org/pubmed/1545122
xref: http://identifiers.org/pubmed/18817510
xref: http://identifiers.org/pubmed/18062768
xref: http://identifiers.org/pubmed/6815536
xref: http://identifiers.org/pubmed/3116143
xref: http://identifiers.org/pubmed/17936914
xref: http://identifiers.org/pubmed/19543225
xref: http://identifiers.org/pubmed/3095922
xref: http://identifiers.org/pubmed/6975347
xref: http://identifiers.org/pubmed/3098894
comment: Interleukin-2 (IL-2) is a cytokine that is produced by T cells in response to antigen stimulation. Originally, IL-2 was discovered because of its potent growth factor activity on activated T cells in vitro and was therefore named 'T cell growth factor' (TCGF). However, the generation of IL-2- and IL-2 receptor-deficient mice revealed that IL-2 also plays a regulatory role in the immune system by suppressing autoimmune responses. Two main mechanisms have been identified that explain this suppressive function: (1) IL-2 sensitizes activated T cells for activation-induced cell death (AICD) and (2) IL-2 is critical for the survival and function of regulatory T cells (Tregs), which possess potent immunosuppressive properties. IL-2 signaling occurs when IL-2 binds to the heterotrimeric high-affinity IL-2 receptor (IL-2R), which consists of alpha, beta and gamma chains. The IL-2R was identified in 1981 via radiolabeled ligand binding (Robb et al. 1981). The IL-2R alpha chain was identified in 1982 (Leonard et al.), the beta chain in 1986/7 (Sharon et al. 1986, Teshigawara et al. 1987) and the IL-2R gamma chain in 1992 (Takeshita et al.). The high affinity of IL-2 binding to the IL-2R is created by a very rapid association rate to the IL-2R alpha chain, combined with a much slower dissociation rate contributed by the combination of the IL-2R beta and gamma chains (Wang & Smith 1987). After antigen stimulation, T cells upregulate the high-affinity IL-2R alpha chain; IL-2R alpha captures IL-2 and this complex then associates with the constitutively expressed IL-2R beta and gamma chains. The IL-2R gamma chain is shared by several other members of the cytokine receptor superfamily including IL-4, IL-7, IL-9, IL-15 and IL-21 receptors, and consequently is often referred to as the Common gamma chain (Gamma-c). The tyrosine kinases Jak1 and Jak3, which are constitutively associated with IL-2R beta and Gamma-c respectively, are activated resulting in phosphorylation of three critica…

UnificationXref265
type: UnificationXref
id: 5615653
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615653

UnificationXref1241
type: UnificationXref
id: 2564802
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564802

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P06838
data source: Provenance1
name: P06838
name: ERCC1, DNA excision repair protein
name: DNA excision repair protein ERCC-1
xref: UnificationXref11583
feature: FragmentFeature1928
cellular location: GO_0005654
comment: Reactome DB_ID: 5610167
display name: ERCC1

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P26754
data source: Provenance1
name: Replication factor-A protein 2
name: RP-A
name: Replication protein A 32 kDa subunit
name: RPA32
name: DNA Replication factor A protein 2 (32kD)
name: P26754
name: RF-A
xref: UnificationXref11572
feature: FragmentFeature1926
cellular location: GO_0005654
comment: Reactome DB_ID: 5607908
display name: RPA2

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P07276
data source: Provenance1
name: DNA excision repair protein ERCC-5
name: DNA-repair protein complementing XP-G cells (Xeroderma pigmentosum group G complementing protein) (DNA excision repair protein ERCC-5)
name: P07276
name: Xeroderma pigmentosum group G complementing protein
name: DNA-repair protein complementing XP-G cells
name: ERCC5 or XPGC
name: XPG protein
xref: UnificationXref11575
feature: FragmentFeature1927
cellular location: GO_0005654
comment: Reactome DB_ID: 5610120
display name: ERCC5

UnificationXref270
type: UnificationXref
id: REACT_233726
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_233726.1

UnificationXref1247
type: UnificationXref
id: REACT_160420
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160420.1

UnificationXref1248
type: UnificationXref
id: CHEBI:18248
db: ChEBI

Assembly of repair proteins at the site of Pol II blockage
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1816
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11632
xref: UnificationXref11631
left: Complex919
left: TFIIH (name copied from entity in Homo sapiens)
left: Note: the coordinates are copied over from Homo sapiens.
left: Complex915
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex919
right: Complex920

UnificationXref1249
type: UnificationXref
id: 71160
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=71160

Formation of active Pol II complex with lesioned DNA template
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1814
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11618
xref: UnificationXref11619
left: Complex918
left: PhysicalEntity172
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex919

P06778
type: Protein
entity reference: P06778
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: DNA repair protein RAD52 homolog
xref: UnificationXref11521
feature: FragmentFeature1920
cellular location: GO_0005654
comment: Reactome DB_ID: 5610606
display name: RAD52

RNA Pol II is blocked by the lesion leading to reduced transcription
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1815
conversion direction: LEFT_TO_RIGHT
xref: RelationshipXref1485
xref: UnificationXref11620
xref: UnificationXref11621
left: Complex919
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex919

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P25454
data source: Provenance1
name: HsRAD51
name: DNA repair protein RAD51 homolog 1
name: P25454
name: DNA repair protein RAD51 homolog 1 (hRAD51) (HsRAD51)
name: hRAD51
xref: UnificationXref11526
feature: FragmentFeature1921
cellular location: GO_0005654
comment: Reactome DB_ID: 5610730
display name: RAD51

3'- incision of DNA by XPG in GG-NER
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1809
conversion direction: LEFT_TO_RIGHT
xref: RelationshipXref1482
xref: UnificationXref11597
xref: UnificationXref11598
left: Complex916
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex917

Ligation of newly synthesized repair patch to incised DNA in GG-NER
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1811
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11608
xref: UnificationXref11607
left: PhysicalEntity169
left: Protein597
left: PhysicalEntity170
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Protein597
right: PhysicalEntity171

MRE11 homolog 1
type: Protein
entity reference: ProteinReference1158
data source: Provenance1
name: Note: the coordinates are copied over from Homo sapiens.
name: P32829
name: Double-strand break repair protein MRE11A
xref: UnificationXref11510
feature: FragmentFeature1919
cellular location: GO_0005654
comment: Reactome DB_ID: 5610508
display name: MRE11A

Formation of ERCC1-XPF heterodimeric complex
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1806
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11587
xref: UnificationXref11588
left: Note: the coordinates are copied over from Homo sapiens.
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex915

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P28519
data source: Provenance1
name: DNA-repair protein complementing XP-A cells
name: xeroderma pigmentosum, complementation group A
name: P28519
name: Xeroderma pigmentosum group A complementing protein
name: DNA-repair protein complementing XP-A cells (Xeroderma pigmentosum group A complementing protein)
name: XPA protein
xref: UnificationXref11568
feature: FragmentFeature1924
cellular location: GO_0005654
comment: Reactome DB_ID: 5610116
display name: XPA

Binding of ERCC1-XPF to preincision complex
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1807
conversion direction: LEFT_TO_RIGHT
xref: RelationshipXref1479
xref: UnificationXref11591
xref: UnificationXref11590
left: Complex915
left: Complex914
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex916

Single-stranded DNA-binding protein
type: Protein
entity reference: P22336
data source: Provenance1
name: RPA70
name: Note: the coordinates are copied over from Homo sapiens.
name: RP-A
name: P22336
name: Replication factor-A protein 1
name: RF-A
name: DNA Replication factor A protein A1 (70kD)
name: Replication protein A 70 kDa DNA-binding subunit
xref: UnificationXref11570
feature: FragmentFeature1925
cellular location: GO_0005654
comment: Reactome DB_ID: 5607903
display name: RPA1

XPC:HR23B complex binds to damaged DNA site with lesion
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1803
conversion direction: LEFT_TO_RIGHT
xref: UnificationXref11563
xref: UnificationXref11564
left: PhysicalEntity159
left: Complex910
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex911

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P14736
data source: Provenance1
name: XPC protein
name: xeroderma pigmentosum, complementation group C
name: Xeroderma pigmentosum group C complementing protein
name: DNA-repair protein complementing XP-C cells (Xeroderma pigmentosum group C complementing protein) (P125)
name: p125
name: DNA-repair protein complementing XP-C cells
name: P14736
xref: UnificationXref11556
feature: FragmentFeature1922
cellular location: GO_0005654
comment: Reactome DB_ID: 5610110
display name: XPC

Formation of open bubble structure in DNA by helicases
type: BiochemicalReaction
data source: Provenance1
evidence: Evidence1805
conversion direction: LEFT_TO_RIGHT
xref: RelationshipXref1478
xref: UnificationXref11580
xref: UnificationXref11581
left: Complex912
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
right: Complex914

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P32628
data source: Provenance1
name: RAD23 homolog B (S. cerevisiae)
name: HR23B, RAD23B homolog protein
name: RAD23B
name: P32628
name: HHR23B
name: UV excision repair protein RAD23 homolog B
name: XP-C repair complementing complex 58 kDa protein
name: UV excision repair protein RAD23 homolog B (HHR23B) (XP-C repair complementing complex 58 kDa protein) (P58)
xref: UnificationXref11558
feature: FragmentFeature1923
cellular location: GO_0005654
comment: Reactome DB_ID: 5610106
display name: P58

Isocitrate dehydrogenase (NAD) subunit 1, mitochondrial
type: Protein
entity reference: P28834
data source: Provenance1
xref: UnificationXref11755
xref: UnificationXref11756
feature: FragmentFeature1949
cellular location: GO_0005829
comment: Reactome DB_ID: 1252188
display name: IDH1

Evidence361
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8755247
xref: http://identifiers.org/pubmed/11498013
comment: GRB2 can bind EGFR directly or through another SH2-containing protein, SHC1. This association leads to RAS activation.

HSP60_YEAST
type: Protein
entity reference: ProteinReference1186
data source: Provenance1
name: Heat shock protein 60, mitochondrial
xref: UnificationXref11753
xref: UnificationXref11752
feature: FragmentFeature1948
cellular location: GO_0005829
comment: Reactome DB_ID: 1252153
display name: HSP60

Evidence360
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/11498013
xref: http://identifiers.org/pubmed/11706405
comment: Autophosphorylated EGFR tyrosine residues are docking sites for many downstream effectors in EGFR signaling. The adaptor protein GRB2 binds to phosphotyrosine residues in the C-tail of EGFR through its SH2 domain. GRB2 is constitutively associated with SOS, a guanine nucleotide exchange factor of RAS. GRB2 binding to phosphorylated EGFR results in the recruitment of SOS to the plasma membrane where it comes in proximity to RAS. This mechanism has been seen to be the model for RAS activation.

Evidence363
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10404636
xref: http://identifiers.org/pubmed/10459005
xref: http://identifiers.org/pubmed/21252999
xref: http://identifiers.org/pubmed/15142631
xref: http://identifiers.org/pubmed/12297041
comment: The epidermal growth factor receptor (EGFR) is one member of the ERBB family of transmembrane glycoprotein tyrosine receptor kinases (RTK). Binding of EGFR to its ligands induces conformational change that unmasks the dimerization interface in the extracellular domain of EGFR, leading to receptor homo- or heterodimerization at the cell surface. Dimerization of the extracellular regions of EGFR triggers additional conformational change of the cytoplasmic EGFR regions, enabling the kinase domains of two EGFR molecules to achieve the catalytically active conformation. Ligand activated EGFR dimers trans-autophosphorylate on tyrosine residues in the cytoplasmic tail of the receptor. Phosphorylated tyrosines serve as binding sites for the recruitment of signal transducers and activators of intracellular substrates, which then stimulate intracellular signal transduction cascades that are involved in regulating cellular proliferation, differentiation, and survival. Recruitment of complexes containing GRB2 and SOS1 to phosphorylated EGFR dimers either directly, through phosphotyrosine residues that serve as GRB2 docking sites, or indirectly, through SHC1 recruitment, promotes GDP to GTP exchange on RAS, resulting in the activation of RAF/MAP kinase cascade. Binding of complexes of GRB2 and GAB1 to phosphorylated EGFR dimers leads to formation of the active PI3K complex, conversion of PIP2 into PIP3, and activation of AKT signaling. Phospholipase C-gamma1 (PLCG1) can also be recruited directly, through EGFR phosphotyrosine residues that serve as PLCG1 docking sites, which leads to PLCG1 phosphorylation by EGFR and activation of DAG and IP3 signaling. EGFR signaling is downregulated by the action of ubiquitin ligase CBL. CBL binds directly to the phosphorylated EGFR dimer through the phosphotyrosine Y1045 in the C-tail of EGFR, and after CBL is phosphorylated by EGFR, it becomes active and ubiquitinates phosphorylated EGFR dimers, targeting them for degradation. For a recent r…

Evidence362
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15550174
comment: GAB1 is recruited to the activated EGFR indirectly, through GRB2. GAB1 acts as an adaptor protein that enables formation of an active PIK3, through recruitment of PIK3 regulatory subunit PIK3R1 (also known as PI3Kp85), which subsequently recruits PIK3 catalytic subunit PIK3CA (also known as PI3Kp110). PIK3, in complex with EGFR, GRB2 and GAB1, catalyzes phosphorylation of PIP2 and its conversion to PIP3, which leads to the activation of the AKT signaling.

Evidence365
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10579907
xref: http://identifiers.org/pubmed/1656221
xref: http://identifiers.org/pubmed/15863030
comment: Phospholipase C-gamma (PLC-gamma) is a substrate of the fibroblast growth factor receptor (FGFR) and other receptors with tyrosine kinase activity. It is known that the src homology region 2 (SH2 domain) of PLC-gamma and of other signaling molecules (such as GTPase-activating protein and phosphatidylinositol 3-kinase-associated p85) direct their binding toward autophosphorylated tyrosine residues of the FGFR. Recruitment of PLC-gamma results in its phosphorylation and activation by the receptor. Activated PLC-gamma hydrolyzes phosphatidyl inositol[4,5] P2 to form the second messengers diacylglycerol (DAG) and Ins [1,4,5]P3, which stimulate calcium release and activation of calcium/calmodulin dependent kinases.

Evidence364
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18452557
xref: http://identifiers.org/pubmed/10377388
xref: http://identifiers.org/pubmed/11447289
xref: http://identifiers.org/pubmed/16682955
xref: http://identifiers.org/pubmed/15863030
xref: http://identifiers.org/pubmed/9182757
comment: The FRS family of scaffolding adaptor proteins has two members, FRS2alpha and FRS2beta (also known as FRS3 or SNT-2). Activation of FGFR tyrosine kinase allows FRS2 proteins to become phosphorylated on tyrosine residues and then bind to the adaptor GRB2 and the tyrosine phosphatase SHP2. Subsequently, SHP2 activates the RAS-MAP kinase pathway and GRB2 activates the RAS-MAP kinase , PI-3-kinase and ubiquitinations/degradation pathways by binding to SOS, GAB1 and CBL, respectively, via the SH3 domains of GRB2. FRS2alpha acts as a central mediator in FGF signaling mainly because it induces sustained levels of activation of ERK with ubiquitous expression.

Evidence367
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/10377388
xref: http://identifiers.org/pubmed/8752212
xref: http://identifiers.org/pubmed/15863030
xref: http://identifiers.org/pubmed/15863038
comment: Signaling via FGFRs is mediated via direct recruitment of signaling proteins that bind to tyrosine auto-phosphorylation sites on the activated receptor and via closely linked docking proteins that become tyrosine phosphorylated in response to FGF-stimulation and form a complex with additional complement of signaling proteins. The activation loop in the catalytic domain of FGFR maintains the PTK domain in an inactive or low activity state. The activation-loop of FGFR1, for instance, contains two tyrosine residues that must be autophosphorylated for maintaining the catalytic domain in an active state. In the autoinhibited configuration, a kinase invariant proline residue at the C-terminal end of the activation loop interferes with substrate binding while allowing access to ATP in the nucleotide binding site. In addition to the catalytic PTK core, the cytoplasmic domain of FGFR contains several regulatory sequences. The juxtamembrane domain of FGFRs is considerably longer than that of other receptor tyrosine kinases. This region contains a highly conserved sequence that serves as a binding site for the phosphotyrosine binding (PTB) domain of FRS2. A variety of signaling proteins are phosphorylated in response to FGF stimulation, including Shc, phospholipase-C gamma and FRS2 leading to stimulation of intracellular signaling pathways that control cell proliferation, cell differentiation, cell migration, cell survival and cell shape.

UnificationXref297
type: UnificationXref
id: REACT_189234
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_189234.3

UnificationXref1231
type: UnificationXref
id: REACT_161355
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_161355.1

Evidence366
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12558974
xref: http://identifiers.org/pubmed/11057895
xref: http://identifiers.org/pubmed/12089343
xref: http://identifiers.org/pubmed/10918587
xref: http://identifiers.org/pubmed/15863030
comment: The ability of growth factors to protect from apoptosis is primarily due to the activation of the AKT survival pathway. P-I-3-kinase dependent activation of PDK leads to the activation of AKT which in turn affects the activity or expression of pro-apoptotic factors, which contribute to protection from apoptosis. AKT activation also blocks the activity of GSK-3b which could lead to additional antiapoptotic signals.

UnificationXref298
type: UnificationXref
id: 5618267
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618267

UnificationXref1230
type: UnificationXref
id: 2564758
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564758

Evidence369
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15239952
xref: http://identifiers.org/pubmed/8388392
comment: p-ERK1/2 dissociates from p-MEK1/2, allowing dimerization of the activated MAPKs and translocation to the nucleus. In FGFR signaling, there is evidence that this dissociation event is negatively regulated by the golgi membrane form of IL17RD, preventing the nuclear localization of activated ERK1/2.

UnificationXref299
type: UnificationXref
id: REACT_243500
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_243500.1

Evidence368
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17035228
xref: http://identifiers.org/pubmed/12958313
xref: http://identifiers.org/pubmed/14742870
xref: http://identifiers.org/pubmed/12807873
xref: http://identifiers.org/pubmed/8388392
comment: MEK1/2 phosphorylate critical tyrosine and threonine residues on ERK1/2, activating the kinase activity of the MAPKs. In FGFR signaling, this reaction appears to be negatively regulated by IL17RD through an unknown mechanism, limiting the extent of MAPK signaling after FGF stimulation.

UnificationXref293
type: UnificationXref
id: REACT_242877
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_242877.1

UnificationXref1235
type: UnificationXref
id: REACT_161432
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_161432.1

UnificationXref294
type: UnificationXref
id: 5618574
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618574

UnificationXref1234
type: UnificationXref
id: 2564811
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564811

UnificationXref295
type: UnificationXref
id: REACT_189062
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_189062.3

UnificationXref1233
type: UnificationXref
id: REACT_160514
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160514.1

UnificationXref296
type: UnificationXref
id: 5618555
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618555

UnificationXref1232
type: UnificationXref
id: 2564801
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564801

UnificationXref1238
type: UnificationXref
id: REACT_160751
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160751.1

UnificationXref1239
type: UnificationXref
id: 2564807
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564807

UnificationXref1236
type: UnificationXref
id: CHEBI:33738
db: ChEBI

UnificationXref1237
type: UnificationXref
id: 2564757
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564757

CYB2 precursor
type: Protein
entity reference: ProteinReference1192
data source: Provenance1
name: CYB2_YEAST
name: Cytochrome b2, mitochondrial
xref: UnificationXref11771
xref: UnificationXref11770
feature: FragmentFeature1954
cellular location: GO_0005829
comment: Reactome DB_ID: 1252093
display name: CYB2

HSP77_YEASX
type: Protein
entity reference: P0CS91
data source: Provenance1
name: Heat shock protein SSC1, mitochondrial
xref: UnificationXref11773
xref: UnificationXref11774
feature: FragmentFeature1955
cellular location: GO_0005829
comment: Reactome DB_ID: 2457653
display name: SSC1

Proteins Imported by TOM40:TOM70 Complex
type: Protein
data source: Provenance1
member physical entity: Protein2448
member physical entity: Protein2447
member physical entity: Protein2449
member physical entity: Protein2444
member physical entity: Protein2443
member physical entity: Protein2446
member physical entity: Protein2445
member physical entity: Protein2452
member physical entity: Protein2453
member physical entity: Protein2440
member physical entity: Protein2441
member physical entity: Protein2450
member physical entity: Protein2442
member physical entity: Protein2451
member physical entity: ADP,ATP carrier protein 1
xref: UnificationXref11808
xref: UnificationXref11807
cellular location: GO_0005758
comment: Reactome DB_ID: 1252210
comment: Converted from EntitySet in Reactome
display name: Cargo of TOM40

http://identifiers.org/pubmed/18403674
type: PublicationXref
id: 18403674
author: Steele, C
author: Mossman, BT
author: Dostert, C
author: Tschopp, J
author: Van Bruggen, R
author: Pétrilli, V
db: Pubmed
title: Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica
source: Science 320:674-7
year: 2008

ADP,ATP carrier protein 1
type: Protein
entity reference: P04710
data source: Provenance1
name: ADT1_YEAST
xref: UnificationXref11778
xref: UnificationXref11777
feature: FragmentFeature1956
cellular location: GO_0005758
comment: Reactome DB_ID: 1252198
display name: AAC1

BCS1_YEAST
type: Protein
entity reference: P32839
data source: Provenance1
name: Mitochondrial chaperone BCS1
xref: UnificationXref11759
xref: UnificationXref11758
feature: FragmentFeature1950
cellular location: GO_0005829
comment: Reactome DB_ID: 1252168
display name: BCS1

TIM22_YEAST
type: Protein
entity reference: D0884
data source: Provenance1
name: Mitochondrial import inner membrane translocase subunit TIM22
xref: UnificationXref11762
xref: UnificationXref11761
feature: FragmentFeature1951
cellular location: GO_0005829
comment: Reactome DB_ID: 1252169
display name: TIM22

Mitochondrial import inner membrane translocase subunit TIM54
type: Protein
entity reference: P47045
data source: Provenance1
name: TIM54_YEAST
xref: UnificationXref11764
xref: UnificationXref11765
feature: FragmentFeature1952
cellular location: GO_0005829
comment: Reactome DB_ID: 1252094
display name: TIM54

Mitochondrial import receptor subunit TOM40
type: Protein
entity reference: P23644
data source: Provenance1
name: TOM40_YEAST
xref: UnificationXref11768
xref: UnificationXref11767
feature: FragmentFeature1953
cellular location: GO_0005829
comment: Reactome DB_ID: 1252146
display name: TOM40

Exonuclease 1
type: Protein
entity reference: P39875
data source: Provenance1
name: P39875
name: Note: the coordinates are copied over from Homo sapiens.
name: EXO1_HUMAN
xref: UnificationXref11691
feature: FragmentFeature1939
cellular location: GO_0005654
comment: Reactome DB_ID: 5617971
display name: EXO1

Evidence372
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Release of phospho-SHC from the insulin receptor triggers a cascade of signalling events via SOS, RAF and the MAP kinases.

Evidence371
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/20602996
xref: http://identifiers.org/pubmed/7917292
xref: http://identifiers.org/pubmed/16597617
xref: http://identifiers.org/pubmed/19247306
xref: http://identifiers.org/pubmed/15567848
xref: http://identifiers.org/pubmed/12080084
xref: http://identifiers.org/pubmed/15863030
xref: http://identifiers.org/pubmed/15863038
comment: The 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosine kinases (RTKs) designated FGFR1, FGFR2, FGFR3 and FGFR4. These receptors are key regulators of several developmental processes in which cell fate and differentiation to various tissue lineages are determined. Unlike other growth factors, FGFs act in concert with heparin or heparan sulfate proteoglycan (HSPG) to activate FGFRs and to induce the pleiotropic responses that lead to the variety of cellular responses induced by this large family of growth factors. An alternative, FGF-independent, source of FGFR activation originates from the interaction with cell adhesion molecules, typically in the context of interactions on neural cell membranes and is crucial for neuronal survival and development. Upon ligand binding, receptor dimers are formed and their intrinsic tyrosine kinase is activated causing phosphorylation of multiple tyrosine residues on the receptors. These then serve as docking sites for the recruitment of SH2 (src homology-2) or PTB (phosphotyrosine binding) domains of adaptors, docking proteins or signaling enzymes. Signaling complexes are assembled and recruited to the active receptors resulting in a cascade of phosphorylation events. This leads to stimulation of intracellular signaling pathways that control cell proliferation, cell differentiation, cell migration, cell survival and cell shape, depending on the cell type or stage of maturation.

Evidence370
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: After being phosphorylated, p-ERK1/2 dissociate from MEK1/2 and dimerize.

Evidence376
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15314020
comment: At the beginning of this reaction, 3 molecules of 'ATP', and 1 molecule of 'eIF4G' are present. At the end of this reaction, 3 molecules of 'ADP', and 1 molecule of 'eIF4G-P' are present. This reaction takes place in the 'cytosol' and is mediated by the 'kinase activity' of 'S6K1-P'.

Evidence375
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15809305
comment: Once phosphorylated, S6K1-P phosphorylates and activates ribosomal protein S6 (rpS6), which in turn selectively increases the translation of 5ââ¬â¢TOP mRNAs. These mRNAs encode exclusively for components of the translation machinery (PMID 15809305).

Evidence374
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15809305
comment: S6K1 contains a TOS motif. mTORC1 requires an intact TOS motif to bind and phosphorylate S6K1 (PMID 15809305).

Evidence373
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: SHC is one of the mediators of insulin signalling events. It is activated by phosphorylation and triggers a cascade of events involving SOS, RAF and the MAP kinases.

UnificationXref288
type: UnificationXref
id: REACT_182529
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_182529.3

UnificationXref289
type: UnificationXref
id: P32364
db: UniProt

UnificationXref286
type: UnificationXref
id: 5615613
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615613

UnificationXref1220
type: UnificationXref
id: REACT_3399
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3399.2

http://identifiers.org/pubmed/9564042
type: PublicationXref
id: 9564042
author: Tobiume, K
author: Takeda, K
author: Ichijo, H
author: Sawada, Y
author: Nishitoh, H
author: Kawabata, M
author: Saitoh, M
author: Miyazono, K
author: Fujii, M
db: Pubmed
title: Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1
source: EMBO J. 17:2596-606
year: 1998

UnificationXref287
type: UnificationXref
id: 5615614
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615614

UnificationXref284
type: UnificationXref
id: P53086
db: UniProt

UnificationXref1222
type: UnificationXref
id: REACT_160484
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160484.1

UnificationXref285
type: UnificationXref
id: 5615612
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615612

UnificationXref1221
type: UnificationXref
id: 2564812
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564812

UnificationXref282
type: UnificationXref
id: 5615620
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615620

UnificationXref1224
type: UnificationXref
id: 2564759
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564759

UnificationXref283
type: UnificationXref
id: REACT_182526
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_182526.3

UnificationXref1223
type: UnificationXref
id: CHEBI:33737
db: ChEBI

UnificationXref292
type: UnificationXref
id: 5615626
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615626

UnificationXref1225
type: UnificationXref
id: REACT_160694
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160694.1

UnificationXref291
type: UnificationXref
id: 5615625
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615625

UnificationXref1226
type: UnificationXref
id: P36152
db: UniProt

http://identifiers.org/pubmed/3208766
type: PublicationXref
id: 3208766
author: Day, IN
author: Fothergill, JE
author: McAleese, SM
author: Hinks, LJ
author: Dunbar, B
db: Pubmed
title: Complete amino acid sequence of the neurone-specific gamma isozyme of enolase (NSE) from human brain and comparison with the non-neuronal alpha form (NNE)
source: Eur J Biochem 178:413-7
year: 1988

UnificationXref290
type: UnificationXref
id: 5615624
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615624

UnificationXref1227
type: UnificationXref
id: 2564777
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564777

UnificationXref1228
type: UnificationXref
id: REACT_160724
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160724.1

UnificationXref1229
type: UnificationXref
id: CHEBI:49883
db: ChEBI

CY1_YEAST
type: Protein
entity reference: P07143
data source: Provenance1
name: Cytochrome c1, heme protein, mitochondrial
xref: UnificationXref11749
xref: UnificationXref11750
feature: FragmentFeature1947
cellular location: GO_0005829
comment: Reactome DB_ID: 1252090
display name: CYT1

http://identifiers.org/pubmed/20930137
type: PublicationXref
id: 20930137
author: Kull, FJ
author: Endow, SA
author: Liu, H
db: Pubmed
title: Kinesins at a glance
source: J Cell Sci 123:3420-4
year: 2010

Aconitate hydratase, mitochondrial
type: Protein
entity reference: P19414
data source: Provenance1
name: ACON_YEAST
xref: UnificationXref11743
xref: UnificationXref11744
feature: FragmentFeature1945
cellular location: GO_0005829
comment: Reactome DB_ID: 1252111
display name: ACO1

Citrate synthase, mitochondrial
type: Protein
entity reference: CIT1
data source: Provenance1
name: CISY1_YEAST
xref: UnificationXref11747
xref: UnificationXref11746
feature: FragmentFeature1946
cellular location: GO_0005829
comment: Reactome DB_ID: 1252092
display name: CIT1

ATPA_YEAST
type: Protein
entity reference: P07251
data source: Provenance1
name: ATP synthase subunit alpha, mitochondrial
name: ATP1 precursor
xref: UnificationXref11738
xref: UnificationXref11737
feature: FragmentFeature1943
cellular location: GO_0005829
comment: Reactome DB_ID: 1252120
display name: ATP1

ATPB_YEAST
type: Protein
entity reference: ProteinReference1182
data source: Provenance1
name: ATP2 precursor
name: ATP synthase subunit beta, mitochondrial
xref: UnificationXref11740
xref: UnificationXref11741
feature: FragmentFeature1944
cellular location: GO_0005829
comment: Reactome DB_ID: 1252203
display name: ATP2

ADP,ATP carrier protein 1
type: Protein
entity reference: P04710
data source: Provenance1
name: ADT1_YEAST
xref: UnificationXref11731
xref: UnificationXref11732
feature: FragmentFeature1941
cellular location: GO_0005829
comment: Reactome DB_ID: 1252151
display name: AAC1

ATP synthase subunit 9, mitochondrial
type: Protein
entity reference: ProteinReference1180
data source: Provenance1
name: ATP9_YEAST
name: ATP9 precursor
xref: UnificationXref11734
xref: UnificationXref11735
feature: FragmentFeature1942
cellular location: GO_0005829
comment: Reactome DB_ID: 1252172
display name: ATP9

Note: the coordinates are copied over from Homo sapiens.
type: Protein
entity reference: P25336
data source: Provenance1
name: P25336
name: MSH3_HUMAN
name: DNA mismatch repair protein Msh3
xref: UnificationXref11704
feature: FragmentFeature1940
cellular location: GO_0005654
comment: Reactome DB_ID: 5617951
display name: MSH3

Proteins Imported by TOM40:TOM70 Complex
type: Protein
data source: Provenance1
member physical entity: Isocitrate dehydrogenase (NAD) subunit 1, mitochondrial
member physical entity: HSP60_YEAST
member physical entity: CY1_YEAST
member physical entity: CYB2 precursor
member physical entity: Aconitate hydratase, mitochondrial
member physical entity: HSP77_YEASX
member physical entity: Citrate synthase, mitochondrial
member physical entity: ATPA_YEAST
member physical entity: ATPB_YEAST
member physical entity: ADP,ATP carrier protein 1
member physical entity: BCS1_YEAST
member physical entity: ATP synthase subunit 9, mitochondrial
member physical entity: TIM22_YEAST
member physical entity: Mitochondrial import inner membrane translocase subunit TIM54
member physical entity: Mitochondrial import receptor subunit TOM40
xref: UnificationXref11776
xref: UnificationXref11775
cellular location: GO_0005829
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 1252224
display name: Cargo of TOM40

UnificationXref1212
type: UnificationXref
id: CHEBI:16238
db: ChEBI

UnificationXref1213
type: UnificationXref
id: 29386
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29386

UnificationXref230
type: UnificationXref
id: 5615201
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615201

UnificationXref1210
type: UnificationXref
id: 112466
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=112466

UniProt:Q00711
type: ProteinReference
name: SDH1
xref: UnificationXref9027
organism: http://identifiers.org/taxonomy/4932

UnificationXref1211
type: UnificationXref
id: REACT_473
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_473.2

Evidence388
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9228007
xref: http://identifiers.org/pubmed/9094314
comment: At the beginning of this reaction, 2 molecules of 'ATP', and 1 molecule of 'PIP3:PKB complex ' are present. At the end of this reaction, 1 molecule of 'PIP3:Phosphorylated PKB complex', and 2 molecules of 'ADP' are present. This reaction takes place on the 'plasma membrane' and is mediated by the 'kinase activity' of 'PIP3:PDK complex [plasma membrane]'.

UnificationXref232
type: UnificationXref
id: 5615207
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615207

http://identifiers.org/pubmed/19540337
type: PublicationXref
id: 19540337
author: Masson, K
author: Rönnstrand, L
db: Pubmed
title: Oncogenic signaling from the hematopoietic growth factor receptors c-Kit and Flt3
source: Cell Signal 21:1717-26
year: 2009

UnificationXref231
type: UnificationXref
id: 5615206
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615206

UnificationXref234
type: UnificationXref
id: GO:0005759
db: GENE ONTOLOGY

UnificationXref233
type: UnificationXref
id: REACT_175066
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_175066.3

Evidence384
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17613433
xref: http://identifiers.org/pubmed/17010524
xref: http://identifiers.org/pubmed/17712357
comment: Upon formation of a trimeric LKB1:STRAD:MO25 complex, LKB1 phosphorylates and activates AMPK. If the AMP:ATP ratio rises, this activation is maintained and AMPK activates the TSC complex by phosphorylating TSC2. Active TSC activates the intrinsic GTPase activity of Rheb, resulting in GDP-loaded Rheb and inhibition of mTOR pathway.

UnificationXref236
type: UnificationXref
id: 159448
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159448

http://identifiers.org/pubmed/9083101
type: PublicationXref
id: 9083101
author: Hosaka, K
author: Nikawa, J
author: Nakashima, A
db: Pubmed
title: Cloning of a human cDNA for CTP-phosphoethanolamine cytidylyltransferase by complementation in vivo of a yeast mutant
source: J Biol Chem 272:9567-72
year: 1997

UnificationXref235
type: UnificationXref
id: CHEBI:16027
db: ChEBI

Evidence386
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: PKB and PDK1 are activated via membrane-bound PIP3. Activated PDK1 phosphorylates PKB, which in turn phosphorylates PDE3B. The latter hydrolyses cAMP to 5'AMP, depleting cAMP pools.

UnificationXref238
type: UnificationXref
id: CHEBI:15996
db: ChEBI

Evidence387
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: At the beginning of this reaction, 1 molecule of '3-phosphoinositide dependent protein kinase-1 ', and 1 molecule of 'Phosphatidylinositol-3,4,5-trisphosphate' are present. At the end of this reaction, 1 molecule of 'PIP3:PDK complex [plasma membrane]' is present. This reaction takes place in the 'cell'.

UnificationXref237
type: UnificationXref
id: REACT_6438
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_6438.3

Evidence380
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8549768
xref: http://identifiers.org/pubmed/16943194
comment: Normally under low AMP:ATP conditions, the active AMPK is dephosphorylated (possibly by PP2C), and thus inactivated.

Evidence381
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8549768
xref: http://identifiers.org/pubmed/16943194
comment: If AMP:ATP ratio rises, AMP (instead of ATP) is bound by the AMPK-gamma subunit, which inhibits the dephosphorylation of the AMPK-alpha subunit resulting in activation of AMPK. It is not clear, as of yet, whether AMP binds to unphosphorylated AMPK.

UnificationXref239
type: UnificationXref
id: 113573
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113573

Evidence382
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/18439900
comment: Activated AMPK (phosphorylated on Thr172/Thr174 and AMP bound) phosphorylates Raptor on Ser 722 and Ser 792. These phosphorylations are required for inhibition of mTORC1 activity in response to energy stress (Gwinn DM et al, 2008).

Evidence383
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17712357
xref: http://identifiers.org/pubmed/18022388
comment: LKB1 forms a complex with STRAD and MO25 thereby attaining a higher activity towards its substrates belonging to the subfamily of AMPK like kinases. LKB1:STRAD:MO25 complex phosphorylates AMPK constantly. This phosphorylation is immediately removed in basal conditions by PP2C, but if the cellular AMP:ATP ratio rises, binding of AMP by AMPK inhibits the dephosphorylation, and the maintained phosphorylation results in activation of the AMPK.

UnificationXref1219
type: UnificationXref
id: 73524
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=73524

UnificationXref1218
type: UnificationXref
id: CHEBI:17621
db: ChEBI

UnificationXref1217
type: UnificationXref
id: REACT_161211
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_161211.1

UnificationXref1216
type: UnificationXref
id: 2564779
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564779

UnificationXref1215
type: UnificationXref
id: Q12181
db: UniProt

UnificationXref1214
type: UnificationXref
id: REACT_4227
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4227.1

UnificationXref1200
type: UnificationXref
id: CHEBI:17677
db: ChEBI

UnificationXref1201
type: UnificationXref
id: 29470
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29470

UnificationXref1202
type: UnificationXref
id: REACT_2826
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2826.1

UnificationXref223
type: UnificationXref
id: 5618265
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618265

UnificationXref222
type: UnificationXref
id: MI:0359
db: MI

Evidence399
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12376548
comment: Once bound by either NGF or proNGF, p75NTR interacts with NRAGE, thus leading to phosphorylation and activation of JUN Kinase (JNK). JNK controls apoptosis in two ways: it induces transcription of pro-apoptotic genes, and directly activates the cell death machinery. Only NGF-bound p75NTR is shown here.

UnificationXref221
type: UnificationXref
id: REACT_240453
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_240453.1

UnificationXref220
type: UnificationXref
id: 5618456
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618456

Evidence397
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Insulin binding to its receptor results in receptor autophosphorylation on tyrosine residues and the tyrosine phosphorylation of insulin receptor substrates (e.g. IRS and Shc) by the insulin receptor tyrosine kinase. This allows association of IRSs with downstream effectors such as PI-3K via its Src homology 2 (SH2) domains leading to end point events such as Glut4 (Slc2a4) translocation. Shc when tyrosine phosphorylated associates with Grb2 and can thus activate the Ras/MAPK pathway independent of the IRSs. Signal transduction by the insulin receptor is not limited to its activation at the cell surface. The activated ligand-receptor complex initially at the cell surface, is internalised into endosomes itself a process which is dependent on tyrosine autophosphorylation. Endocytosis of activated receptors has the dual effect of concentrating receptors within endosomes and allows the insulin receptor tyrosine kinase to phosphorylate substrates that are spatially distinct from those accessible at the plasma membrane. Acidification of the endosomal lumen, due to the presence of proton pumps, results in dissociation of insulin from its receptor. (The endosome constitutes the major site of insulin degradation). This loss of the ligand-receptor complex attenuates any further insulin-driven receptor re-phosphorylation events and leads to receptor dephosphorylation by extra-lumenal endosomally-associated protein tyrosine phosphatases (PTPs). The identity of these PTPs is not clearly established yet. A discussion of candidates will be added in the near future.

UnificationXref227
type: UnificationXref
id: P13517
db: UniProt

Evidence398
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/12097334
comment: The different molecules listed (NRAGE, NRIF, NADE, TRAF6) mediate, through unclear mechanisms, JNK activation by threonine and tyrosine phosphorylation. While active JNK does move to the nucleus and phosphorylates and activate transcription factors such as c-JUN and ATF2, these have not been implicated in p75-mediated cell death, but rather the direct activation of the cell death machinery by JNK has been implicated. p75 activates the intrinsic caspase pathway (involving mitochondrial release of cytochrome c, Apaf-1, and caspases-9) rather than the extrinsic (caspase-8) pathway activated by most other death receptors.

UnificationXref226
type: UnificationXref
id: REACT_252862
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_252862.1

Evidence395
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/8682206
xref: http://identifiers.org/pubmed/9793760
xref: http://identifiers.org/pubmed/3061785
comment: The effect of the proton pump is to allow entry of [H+] ions into the lumen of the endosome. The net effect of this is to lower the pH of the lumen from pH 7.4 (the pH at the plasma membrane) to pH 6.0 (documented with studies using FITC-labeled insulin - a pH dependent fluorescence marker).

UnificationXref225
type: UnificationXref
id: 5618266
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618266

Evidence396
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Triggered by acidification of the endosome, insulin dissociates from the receptor and is degraded. The receptor is dephosphorylated and re-integrated into the plasma membrane, ready to be activated again by the binding of insulin molecules.

UnificationXref224
type: UnificationXref
id: REACT_238594
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_238594.1

Evidence393
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: IRS is one of the mediators of insulin signalling events. It is activated by phosphorylation and triggers a cascade of events involving PI3K, SOS, RAF and the MAP kinases. The proteins mentioned under IRS are examples of IRS family members acting as indicated. More family members are to be confirmed and added in the future.

Evidence394
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9677303
xref: http://identifiers.org/pubmed/11282018
comment: Autophosphorylation of the insulin receptor triggers a series of signalling events, mediated by SHC or IRS, and resulting in activation of the Ras/RAF and MAP kinase cascades. A second effect of the autophosphorylation of the insulin receptor is its internalisation into an endosome, which downregulates its signalling activity.

Evidence391
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: SOS is recruited to the plasma membrane and mediates activation of Ras.

UnificationXref229
type: UnificationXref
id: P28495
db: UniProt

Evidence392
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Release of phospho-IRS from the insulin receptor triggers a cascade of signalling events via PI3K, SOS, RAF and the MAP kinases.

UnificationXref228
type: UnificationXref
id: 5615205
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615205

UnificationXref1208
type: UnificationXref
id: 30595
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=30595

UnificationXref1207
type: UnificationXref
id: REACT_3782
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3782.1

UnificationXref1209
type: UnificationXref
id: REACT_4491
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4491.1

http://identifiers.org/pubmed/9305837
type: PublicationXref
id: 9305837
author: Mäder, A W
author: Luger, K
author: Richmond, R K
author: Sargent, D F
author: Richmond, T J
db: Pubmed
title: Crystal structure of the nucleosome core particle at 2.8 A resolution
source: Nature 389:251-60
year: 1997

UnificationXref1204
type: UnificationXref
id: REACT_5587
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5587.1

UnificationXref1203
type: UnificationXref
id: 113571
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113571

UnificationXref1206
type: UnificationXref
id: 113562
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113562

UnificationXref1205
type: UnificationXref
id: CHEBI:15713
db: ChEBI

UnificationXref254
type: UnificationXref
id: 5615659
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615659

UnificationXref253
type: UnificationXref
id: P36019
db: UniProt

UnificationXref256
type: UnificationXref
id: 5615663
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615663

UnificationXref255
type: UnificationXref
id: P36017
db: UniProt

UnificationXref250
type: UnificationXref
id: GO:0010008
db: GENE ONTOLOGY

UnificationXref252
type: UnificationXref
id: 5615672
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615672

UnificationXref251
type: UnificationXref
id: P38932
db: UniProt

UnificationXref258
type: UnificationXref
id: P32609
db: UniProt

UnificationXref257
type: UnificationXref
id: 5615664
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615664

UnificationXref259
type: UnificationXref
id: 5615668
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615668

http://identifiers.org/pubmed/10958654
type: PublicationXref
id: 10958654
author: Vincent, MF
author: Marie, S
author: Van den Berghe, G
author: Race, V
db: Pubmed
title: Clinical, biochemical and molecular genetic correlations in adenylosuccinate lyase deficiency
source: Hum Mol Genet 9:2159-2165
year: 2000

UnificationXref245
type: UnificationXref
id: REACT_4478
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4478.1

UnificationXref244
type: UnificationXref
id: 113581
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113581

UnificationXref243
type: UnificationXref
id: REACT_3998
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3998.1

UnificationXref242
type: UnificationXref
id: 113525
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113525

UnificationXref241
type: UnificationXref
id: CHEBI:17552
db: ChEBI

UniProt:Q12375
type: ProteinReference
name: ORT1
xref: UnificationXref9999
organism: http://identifiers.org/taxonomy/4932

http://identifiers.org/pubmed/19767751
type: PublicationXref
id: 19767751
author: Kosako, H
author: Hattori, S
author: Taniguchi, H
author: Kose, S
author: Ushiyama, M
author: Nishida, E
author: Imamoto, N
author: Aranami, C
author: Yamaguchi, N
db: Pubmed
title: Phosphoproteomics reveals new ERK MAP kinase targets and links ERK to nucleoporin-mediated nuclear transport
source: Nat Struct Mol Biol 16:1026-35
year: 2009

ATG21
type: ProteinReference
name: UniProt:Q02887
xref: UnificationXref5316
organism: http://identifiers.org/taxonomy/4932

UnificationXref240
type: UnificationXref
id: REACT_4430
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_4430.1

http://identifiers.org/pubmed/17765544
type: PublicationXref
id: 17765544
author: Cote, Jean-Francois
author: Vuori, K
db: Pubmed
title: GEF what? Dock180 and related proteins help Rac to polarize cells in new ways
source: Trends Cell Biol 17:383-93
year: 2007

UniProt:Q02883
type: ProteinReference
name: FMP30
xref: UnificationXref3259
organism: http://identifiers.org/taxonomy/4932

UniProt:Q12377
type: ProteinReference
name: RPN6
xref: UnificationXref462
organism: http://identifiers.org/taxonomy/4932

UnificationXref249
type: UnificationXref
id: REACT_182860
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_182860.3

UnificationXref248
type: UnificationXref
id: 5615648
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615648

UnificationXref247
type: UnificationXref
id: 5615646
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615646

UnificationXref246
type: UnificationXref
id: P26364
db: UniProt

CYB2
type: ProteinReference
name: UniProt:P00175
xref: UnificationXref10132
organism: http://identifiers.org/taxonomy/4932

UniProt:P49089
type: ProteinReference
name: ASN1
xref: UnificationXref5331
organism: http://identifiers.org/taxonomy/4932

http://identifiers.org/pubmed/12151002
type: PublicationXref
id: 12151002
author: Paiement, J
author: Desjardins, M
author: Bergeron, JJ
author: Cameron, PH
author: Duclos, S
author: Chevet, E
author: Gagnon, E
author: Steele-Mortimer, O
author: Rondeau, C
db: Pubmed
title: Endoplasmic reticulum-mediated phagocytosis is a mechanism of entry into macrophages
source: Cell 110:119-31
year: 2002

UnificationXref9934
type: UnificationXref
id: 5608791
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608791

SequenceSite288
type: SequenceSite
position status: EQUAL
sequence position: 1

Stoichiometry1571
type: Stoichiometry
physical entity: Protein1601
stoichiometric coefficient: 3.0

UnificationXref9933
type: UnificationXref
id: 5608789
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608789

SequenceSite289
type: SequenceSite
position status: EQUAL
sequence position: 201

Stoichiometry1570
type: Stoichiometry
physical entity: Protein1598
stoichiometric coefficient: 1.0

UnificationXref9936
type: UnificationXref
id: 893607
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=893607

SequenceSite286
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref9935
type: UnificationXref
id: REACT_245207
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_245207.1

SequenceSite287
type: SequenceSite
position status: EQUAL
sequence position: 226

UnificationXref9930
type: UnificationXref
id: REACT_2656
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2656.2

SequenceSite284
type: SequenceSite
position status: EQUAL
sequence position: 35

SequenceSite285
type: SequenceSite
position status: EQUAL
sequence position: 239

UnificationXref9932
type: UnificationXref
id: 5608788
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608788

SequenceSite282
type: SequenceSite
position status: EQUAL
sequence position: 1

Depolymerisation of the Nuclear Lamina
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction63
pathway component: BiochemicalReaction62
pathway component: BiochemicalReaction61
evidence: Evidence93
xref: UnificationXref1364
xref: UnificationXref1363
pathway order: PathwayStep91
pathway order: PathwayStep90
pathway order: PathwayStep89
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref9931
type: UnificationXref
id: P47096
db: UniProt

SequenceSite283
type: SequenceSite
position status: EQUAL
sequence position: 377

Stoichiometry1579
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

Stoichiometry1578
type: Stoichiometry
physical entity: Protein1608
stoichiometric coefficient: 4.0

Stoichiometry1577
type: Stoichiometry
physical entity: Protein1605
stoichiometric coefficient: 4.0

Stoichiometry1576
type: Stoichiometry
physical entity: Protein1604
stoichiometric coefficient: 2.0

Stoichiometry1575
type: Stoichiometry
physical entity: Protein1601
stoichiometric coefficient: 1.0

Stoichiometry1574
type: Stoichiometry
physical entity: Protein1598
stoichiometric coefficient: 3.0

Stoichiometry1573
type: Stoichiometry
physical entity: Protein1601
stoichiometric coefficient: 2.0

Stoichiometry1572
type: Stoichiometry
physical entity: Protein1598
stoichiometric coefficient: 2.0

SequenceSite281
type: SequenceSite
position status: EQUAL
sequence position: 234

SequenceSite280
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref9937
type: UnificationXref
id: REACT_27004
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_27004.2

UnificationXref9938
type: UnificationXref
id: 893617
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=893617

UnificationXref9939
type: UnificationXref
id: REACT_25814
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_25814.1

UnificationXref9925
type: UnificationXref
id: 5608782
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608782

SequenceSite297
type: SequenceSite
position status: EQUAL
sequence position: 263

http://identifiers.org/pubmed/1717476
type: PublicationXref
id: 1717476
author: Hunter, T
author: Pines, J
db: Pubmed
title: Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport
source: J Cell Biol 115:1-17
year: 1991

UnificationXref9924
type: UnificationXref
id: 5608781
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608781

SequenceSite298
type: SequenceSite
position status: EQUAL
sequence position: 73

UnificationXref9923
type: UnificationXref
id: Q05979
db: UniProt

SequenceSite299
type: SequenceSite
position status: EQUAL
sequence position: 276

Stoichiometry1560
type: Stoichiometry
physical entity: SmallMolecule54
stoichiometric coefficient: 2.0

UnificationXref9922
type: UnificationXref
id: REACT_3123
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3123.2

UnificationXref9921
type: UnificationXref
id: 30487
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=30487

SequenceSite293
type: SequenceSite
position status: EQUAL
sequence position: 277

UnificationXref9920
type: UnificationXref
id: CHEBI:15793
db: ChEBI

SequenceSite294
type: SequenceSite
position status: EQUAL
sequence position: 29

SequenceSite295
type: SequenceSite
position status: EQUAL
sequence position: 241

SequenceSite296
type: SequenceSite
position status: EQUAL
sequence position: 1

Stoichiometry1566
type: Stoichiometry
physical entity: Protein1596
stoichiometric coefficient: 2.0

Stoichiometry1565
type: Stoichiometry
physical entity: Protein1595
stoichiometric coefficient: 2.0

Stoichiometry1568
type: Stoichiometry
physical entity: Protein1598
stoichiometric coefficient: 4.0

Stoichiometry1567
type: Stoichiometry
physical entity: Protein1597
stoichiometric coefficient: 2.0

Stoichiometry1562
type: Stoichiometry
physical entity: Protein724
stoichiometric coefficient: 1.0

Stoichiometry1561
type: Stoichiometry
physical entity: Protein1594
stoichiometric coefficient: 2.0

Stoichiometry1564
type: Stoichiometry
physical entity: Protein730
stoichiometric coefficient: 1.0

Stoichiometry1563
type: Stoichiometry
physical entity: Protein733
stoichiometric coefficient: 1.0

http://identifiers.org/pubmed/11347887
type: PublicationXref
id: 11347887
author: Hou, YM
author: King, MP
author: Davidson, E
author: Vitseva, O
author: Caffarella, J
db: Pubmed
title: Isolation of two cDNAs encoding functional human cytoplasmic cysteinyl-tRNA synthetase
source: Biol Chem 382:399-406
year: 2001

Stoichiometry1569
type: Stoichiometry
physical entity: Protein1601
stoichiometric coefficient: 4.0

SequenceSite290
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite292
type: SequenceSite
position status: EQUAL
sequence position: 44

UniProt:Q12354
type: ProteinReference
name: S000004108
xref: UnificationXref8889
organism: http://identifiers.org/taxonomy/4932

SequenceSite291
type: SequenceSite
position status: EQUAL
sequence position: 534

UnificationXref9928
type: UnificationXref
id: CHEBI:29044
db: ChEBI

UnificationXref9929
type: UnificationXref
id: 36027
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=36027

UnificationXref9926
type: UnificationXref
id: 5608784
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608784

UnificationXref9927
type: UnificationXref
id: REACT_261844
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_261844.1

SequenceSite262
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite263
type: SequenceSite
position status: EQUAL
sequence position: 248

UnificationXref9910
type: UnificationXref
id: 5615299
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615299

SequenceSite260
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite261
type: SequenceSite
position status: EQUAL
sequence position: 418

UnificationXref9912
type: UnificationXref
id: REACT_261346
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_261346.1

SequenceSite266
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref9911
type: UnificationXref
id: 5615301
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615301

SequenceSite267
type: SequenceSite
position status: EQUAL
sequence position: 439

UnificationXref9914
type: UnificationXref
id: 34351
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=34351

SequenceSite264
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref9913
type: UnificationXref
id: CHEBI:17380
db: ChEBI

SequenceSite265
type: SequenceSite
position status: EQUAL
sequence position: 456

Stoichiometry1553
type: Stoichiometry
physical entity: SmallMolecule12
stoichiometric coefficient: 4.0

Stoichiometry1552
type: Stoichiometry
physical entity: Protein1586
stoichiometric coefficient: 4.0

SequenceSite268
type: SequenceSite
position status: EQUAL
sequence position: 2

Stoichiometry1551
type: Stoichiometry
physical entity: Protein1585
stoichiometric coefficient: 4.0

SequenceSite269
type: SequenceSite
position status: EQUAL
sequence position: 406

Stoichiometry1550
type: Stoichiometry
physical entity: Protein691
stoichiometric coefficient: 4.0

Stoichiometry1557
type: Stoichiometry
physical entity: Protein1592
stoichiometric coefficient: 2.0

http://identifiers.org/pubmed/14699086
type: PublicationXref
id: 14699086
author: Vigneron, Marc
author: Metz, Alexandra
author: Turner, Bryan M
author: Govin, Jérôme
author: Jolly, Caroline
author: Vourc'h, Claire
author: Khochbin, Saadi
db: Pubmed
title: Stress-induced transcription of satellite III repeats
source: J. Cell Biol. 164:25-33
year: 2004

Stoichiometry1556
type: Stoichiometry
physical entity: SmallMolecule12
stoichiometric coefficient: 4.0

Stoichiometry1555
type: Stoichiometry
physical entity: SmallMolecule396
stoichiometric coefficient: 1.0

http://identifiers.org/pubmed/10413847
type: PublicationXref
id: 10413847
author: Bläker, M
author: de Weerth, A
author: von Schrenck, T
db: Pubmed
title: [Receptors for cholecystokinin and gastrin]
source: Z Gastroenterol 37:389-401
year: 1999

Stoichiometry1554
type: Stoichiometry
physical entity: Complex505
stoichiometric coefficient: 1.0

GYP5
type: ProteinReference
name: UniProt:Q12344
xref: UnificationXref12201
organism: http://identifiers.org/taxonomy/4932

Stoichiometry1558
type: Stoichiometry
physical entity: Protein1593
stoichiometric coefficient: 2.0

Stoichiometry1559
type: Stoichiometry
physical entity: SmallMolecule15
stoichiometric coefficient: 2.0

UnificationXref9915
type: UnificationXref
id: REACT_3577
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_3577.1

UnificationXref9916
type: UnificationXref
id: P38169
db: UniProt

UnificationXref9917
type: UnificationXref
id: 5608774
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608774

UnificationXref9918
type: UnificationXref
id: 5608776
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5608776

UnificationXref9919
type: UnificationXref
id: REACT_231593
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_231593.1

SequenceSite271
type: SequenceSite
position status: EQUAL
sequence position: 223

SequenceSite272
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite273
type: SequenceSite
position status: EQUAL
sequence position: 389

SequenceSite274
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref9903
type: UnificationXref
id: 5612611
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5612611

SequenceSite275
type: SequenceSite
position status: EQUAL
sequence position: 1843

UnificationXref9902
type: UnificationXref
id: 5612609
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5612609

SequenceSite276
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref9901
type: UnificationXref
id: 5612608
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5612608

SequenceSite277
type: SequenceSite
position status: EQUAL
sequence position: 256

UnificationXref9900
type: UnificationXref
id: P47125
db: UniProt

SequenceSite278
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite279
type: SequenceSite
position status: EQUAL
sequence position: 246

Stoichiometry1540
type: Stoichiometry
physical entity: SmallMolecule77
stoichiometric coefficient: 1.0

Stoichiometry1542
type: Stoichiometry
physical entity: PDPK1:PIP2 (name copied from entity in Homo sapiens)
stoichiometric coefficient: 1.0

Stoichiometry1541
type: Stoichiometry
physical entity: Protein1565
stoichiometric coefficient: 1.0

Stoichiometry1544
type: Stoichiometry
physical entity: SmallMolecule36
stoichiometric coefficient: 2.0

Stoichiometry1543
type: Stoichiometry
physical entity: Complex498
stoichiometric coefficient: 1.0

Stoichiometry1546
type: Stoichiometry
physical entity: SmallMolecule381
stoichiometric coefficient: 1.0

Stoichiometry1545
type: Stoichiometry
physical entity: SmallMolecule37
stoichiometric coefficient: 2.0

Stoichiometry1547
type: Stoichiometry
physical entity: PhysicalEntity133
stoichiometric coefficient: 1.0

Stoichiometry1548
type: Stoichiometry
physical entity: Protein1577
stoichiometric coefficient: 2.0

Stoichiometry1549
type: Stoichiometry
physical entity: SmallMolecule388
stoichiometric coefficient: 2.0

http://identifiers.org/pubmed/19196647
type: PublicationXref
id: 19196647
author: De Camilli, Pietro
author: McCrea, HJ
db: Pubmed
title: Mutations in phosphoinositide metabolizing enzymes and human disease
source: Physiology (Bethesda) 24:8-16
year: 2009

UnificationXref9906
type: UnificationXref
id: 5615266
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615266

UnificationXref9907
type: UnificationXref
id: 5615268
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615268

UnificationXref9904
type: UnificationXref
id: REACT_215539
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_215539.2

UnificationXref9905
type: UnificationXref
id: 5615265
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615265

SME1
type: ProteinReference
name: UniProt:Q12330
xref: UnificationXref3680
organism: http://identifiers.org/taxonomy/4932

UnificationXref9908
type: UnificationXref
id: REACT_233794
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_233794.1

SequenceSite270
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref9909
type: UnificationXref
id: 5615298
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615298

SequenceSite249
type: SequenceSite
position status: EQUAL
sequence position: 440

SequenceSite248
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite247
type: SequenceSite
position status: EQUAL
sequence position: 264

SequenceSite246
type: SequenceSite
position status: EQUAL
sequence position: 46

SequenceSite245
type: SequenceSite
position status: EQUAL
sequence position: 376

SequenceSite244
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite243
type: SequenceSite
position status: EQUAL
sequence position: 241

SequenceSite242
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite241
type: SequenceSite
position status: EQUAL
sequence position: 263

SequenceSite240
type: SequenceSite
position status: EQUAL
sequence position: 60

UnificationXref1298
type: UnificationXref
id: 2564787
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564787

UnificationXref1299
type: UnificationXref
id: REACT_161207
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_161207.1

UnificationXref1294
type: UnificationXref
id: 2564795
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564795

UnificationXref1295
type: UnificationXref
id: REACT_160351
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160351.1

UnificationXref1296
type: UnificationXref
id: 2564796
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564796

UnificationXref1297
type: UnificationXref
id: REACT_160339
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160339.1

UnificationXref1290
type: UnificationXref
id: 2564816
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564816

D0884
type: ProteinReference
name: YDL217C
name: UniProt:Q12328 TIM22
name: TIM22
xref: UnificationXref11760
comment: SIMILARITY Belongs to the Tim17/Tim22/Tim23 family.
organism: http://identifiers.org/taxonomy/4932

UnificationXref1291
type: UnificationXref
id: REACT_161330
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_161330.1

UnificationXref1292
type: UnificationXref
id: 2564813
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564813

UniProt:Q12326
type: ProteinReference
name: GPM3
xref: UnificationXref6205
organism: http://identifiers.org/taxonomy/4932

UnificationXref1293
type: UnificationXref
id: REACT_161210
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_161210.1

SequenceSite258
type: SequenceSite
position status: EQUAL
sequence position: 50

SequenceSite257
type: SequenceSite
position status: EQUAL
sequence position: 255

SequenceSite259
type: SequenceSite
position status: EQUAL
sequence position: 300

SequenceSite254
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite253
type: SequenceSite
position status: EQUAL
sequence position: 205

SequenceSite256
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite255
type: SequenceSite
position status: EQUAL
sequence position: 433

SequenceSite250
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite252
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite251
type: SequenceSite
position status: EQUAL
sequence position: 389

UnificationXref1289
type: UnificationXref
id: REACT_161101
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_161101.1

UnificationXref1287
type: UnificationXref
id: P23503
db: UniProt

UnificationXref1288
type: UnificationXref
id: 2564785
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564785

UnificationXref1285
type: UnificationXref
id: 2564773
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564773

UnificationXref1286
type: UnificationXref
id: REACT_160409
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160409.1

UnificationXref1283
type: UnificationXref
id: REACT_160674
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160674.1

UnificationXref1284
type: UnificationXref
id: P38829
db: UniProt

UnificationXref1281
type: UnificationXref
id: P40469
db: UniProt

UnificationXref1282
type: UnificationXref
id: 2564782
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564782

http://identifiers.org/pubmed/17637696
type: PublicationXref
id: 17637696
author: Gerondakis, S
author: Banerjee, A
db: Pubmed
title: Coordinating TLR-activated signaling pathways in cells of the immune system
source: Immunol Cell Biol 85:420-4
year: 2007

Hyaluronan metabolism
type: Pathway
data source: Provenance1
pathway component: REACT 209595.2
evidence: Evidence875
xref: UnificationXref5907
xref: RelationshipXref509
xref: UnificationXref5908
pathway order: PathwayStep859
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref1280
type: UnificationXref
id: REACT_161135
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_161135.1

NTO1
type: ProteinReference
name: UniProt:Q12311
xref: UnificationXref192
organism: http://identifiers.org/taxonomy/4932

SequenceSite227
type: SequenceSite
position status: EQUAL
sequence position: 532

Stoichiometry1596
type: Stoichiometry
physical entity: SmallMolecule335
stoichiometric coefficient: 1.0

SequenceSite226
type: SequenceSite
position status: EQUAL
sequence position: 457

Stoichiometry1597
type: Stoichiometry
physical entity: SmallMolecule410
stoichiometric coefficient: 4.0

SequenceSite225
type: SequenceSite
position status: EQUAL
sequence position: 456

Stoichiometry1594
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

http://identifiers.org/pubmed/21029861
type: PublicationXref
id: 21029861
author: Hogg, JR
author: Goff, SP
db: Pubmed
title: Upf1 senses 3'UTR length to potentiate mRNA decay
source: Cell 143:379-89
year: 2010

SequenceSite224
type: SequenceSite
position status: EQUAL
sequence position: 381

Stoichiometry1595
type: Stoichiometry
physical entity: Protein1627
stoichiometric coefficient: 4.0

http://identifiers.org/pubmed/11278511
type: PublicationXref
id: 11278511
author: Ding, WC
author: Berger, SH
author: Lebioda, L
author: Koli, S
author: Minor, W
author: Dunlap, RB
author: Phan, J
author: Steadman, DJ
db: Pubmed
title: Structure of human thymidylate synthase suggests advantages of chemotherapy with noncompetitive inhibitors
source: J Biol Chem 276:14170-7
year: 2001

SequenceSite229
type: SequenceSite
position status: EQUAL
sequence position: 608

Stoichiometry1598
type: Stoichiometry
physical entity: Protein1630
stoichiometric coefficient: 2.0

SequenceSite228
type: SequenceSite
position status: EQUAL
sequence position: 533

Stoichiometry1599
type: Stoichiometry
physical entity: Protein1635
stoichiometric coefficient: 2.0

SequenceSite223
type: SequenceSite
position status: EQUAL
sequence position: 380

Stoichiometry1592
type: Stoichiometry
physical entity: SmallMolecule407
stoichiometric coefficient: 1.0

SequenceSite222
type: SequenceSite
position status: EQUAL
sequence position: 305

Stoichiometry1593
type: Stoichiometry
physical entity: Protein692
stoichiometric coefficient: 4.0

SequenceSite221
type: SequenceSite
position status: EQUAL
sequence position: 304

Stoichiometry1590
type: Stoichiometry
physical entity: SmallMolecule407
stoichiometric coefficient: 1.0

SequenceSite220
type: SequenceSite
position status: EQUAL
sequence position: 229

Stoichiometry1591
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

UnificationXref1272
type: UnificationXref
id: REACT_160697
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160697.1

UnificationXref1273
type: UnificationXref
id: P38859
db: UniProt

Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.
type: Pathway
data source: Provenance1
pathway component: REACT 262456.1
evidence: Evidence1420
xref: UnificationXref9112
xref: UnificationXref9113
xref: RelationshipXref1078
pathway order: PathwayStep1403
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

UnificationXref1274
type: UnificationXref
id: 2564783
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564783

Interconversion of 2-oxoglutarate and 2-hydroxyglutarate
type: Pathway
data source: Provenance1
pathway component: BiochemicalReaction833
pathway component: BiochemicalReaction832
pathway component: BiochemicalReaction831
evidence: Evidence1414
xref: RelationshipXref523
xref: UnificationXref9083
xref: UnificationXref9082
pathway order: PathwayStep1397
pathway order: PathwayStep1396
pathway order: PathwayStep1395
comment: This event has been computationally inferred from an event that has been demonstrated in another species. The inference is based on the homology mapping in Ensembl Compara. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation. More details and caveats of the event inference in Reactome. For details on the Ensembl Compara system see also: Gene orthology/paralogy prediction method.
organism: http://identifiers.org/taxonomy/4932

http://identifiers.org/pubmed/10625641
type: PublicationXref
id: 10625641
author: Lopez-Jimenez, M
author: Ramesh, B
author: Srai, SK
author: Dedes, M
author: Williams, M
author: Leggett, A
author: Sharp, P
author: Tandy, S
db: Pubmed
title: Nramp2 expression is associated with pH-dependent iron uptake across the apical membrane of human intestinal Caco-2 cells
source: J Biol Chem 275:1023-9
year: 2000

UnificationXref1275
type: UnificationXref
id: REACT_160600
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160600.1

UnificationXref1276
type: UnificationXref
id: 2564792
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564792

UnificationXref1277
type: UnificationXref
id: REACT_161362
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_161362.1

UnificationXref1278
type: UnificationXref
id: Q05583
db: UniProt

UnificationXref1279
type: UnificationXref
id: 2564768
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564768

UniProt:Q12306
type: ProteinReference
name: SMT3
xref: UnificationXref5061
organism: http://identifiers.org/taxonomy/4932

UnificationXref1270
type: UnificationXref
id: P06839
db: UniProt

UnificationXref1271
type: UnificationXref
id: 2564780
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564780

http://identifiers.org/pubmed/16143825
type: PublicationXref
id: 16143825
author: Briere, JJ
author: El Ghouzzi, V
author: Djouadi, F
author: Favier, J
author: Gimenez, AP
author: Benit, P
author: Rustin, P
db: Pubmed
title: Succinate dehydrogenase deficiency in human
source: Cell Mol Life Sci 62:2317â2324
year: 2005

SequenceSite236
type: SequenceSite
position status: EQUAL
sequence position: 1

Stoichiometry1583
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

SequenceSite235
type: SequenceSite
position status: EQUAL
sequence position: 310

Stoichiometry1584
type: Stoichiometry
physical entity: Protein1618
stoichiometric coefficient: 2.0

SequenceSite238
type: SequenceSite
position status: EQUAL
sequence position: 1

Stoichiometry1585
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

SequenceSite237
type: SequenceSite
position status: EQUAL
sequence position: 261

Stoichiometry1586
type: Stoichiometry
physical entity: Protein1622
stoichiometric coefficient: 2.0

Stoichiometry1587
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

SequenceSite239
type: SequenceSite
position status: EQUAL
sequence position: 350

Stoichiometry1588
type: Stoichiometry
physical entity: Protein1623
stoichiometric coefficient: 2.0

Stoichiometry1589
type: Stoichiometry
physical entity: Protein1624
stoichiometric coefficient: 4.0

http://identifiers.org/pubmed/21253609
type: PublicationXref
id: 21253609
author: Batista-Nascimento, Liliana
author: Rodrigues-Pousada, Claudina
author: Liu, Phillip C C
author: Neef, Daniel W
author: Thiele, Dennis J
db: Pubmed
title: Deciphering human heat shock transcription factor 1 regulation via post-translational modification in yeast
source: PLoS ONE 6:e15976
year: 2011

http://identifiers.org/pubmed/9477959
type: PublicationXref
id: 9477959
author: Gould, GW
author: De la Rue, SA
author: Porter, LM
author: Seatter, MJ
db: Pubmed
title: QLS motif in transmembrane helix VII of the glucose transporter family interacts with the C-1 position of D-glucose and is involved in substrate selection at the exofacial binding site.
source: Biochemistry 37:1322-6
year: 1998

SequenceSite230
type: SequenceSite
position status: EQUAL
sequence position: 609

UnificationXref1269
type: UnificationXref
id: REACT_161192
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_161192.1

SequenceSite232
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite231
type: SequenceSite
position status: EQUAL
sequence position: 684

Stoichiometry1580
type: Stoichiometry
physical entity: Protein1609
stoichiometric coefficient: 1.0

http://identifiers.org/pubmed/10536157
type: PublicationXref
id: 10536157
author: Wu, X
author: Zhang, Y
author: Xin, H
author: Lin, W
author: Yuan, F
db: Pubmed
title: The human REV1 gene codes for a DNA template-dependent dCMP transferase.
source: Nucleic Acids Res 27:4468-75
year: 1999

SequenceSite234
type: SequenceSite
position status: EQUAL
sequence position: 1

Stoichiometry1581
type: Stoichiometry
physical entity: Protein1610
stoichiometric coefficient: 2.0

SequenceSite233
type: SequenceSite
position status: EQUAL
sequence position: 324

Stoichiometry1582
type: Stoichiometry
physical entity: Protein1614
stoichiometric coefficient: 2.0

UnificationXref1263
type: UnificationXref
id: 2564766
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564766

http://identifiers.org/pubmed/18538142
type: PublicationXref
id: 18538142
author: Hunt, MC
author: Alexson, SE
db: Pubmed
title: Novel functions of acyl-CoA thioesterases and acyltransferases as auxiliary enzymes in peroxisomal lipid metabolism
source: Prog Lipid Res 47:405-21
year: 2008

UnificationXref1264
type: UnificationXref
id: REACT_160997
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160997.1

UnificationXref1261
type: UnificationXref
id: GO:0005743
db: GENE ONTOLOGY

UnificationXref1262
type: UnificationXref
id: P40416
db: UniProt

UnificationXref1267
type: UnificationXref
id: P15436
db: UniProt

UnificationXref1268
type: UnificationXref
id: 2564774
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564774

UnificationXref1265
type: UnificationXref
id: 2564822
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2564822

UnificationXref1266
type: UnificationXref
id: REACT_160261
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160261.3

http://identifiers.org/pubmed/16483568
type: PublicationXref
id: 16483568
author: Da Silva, CA
author: Frossard, N
author: Reber, L
db: Pubmed
title: Stem cell factor and its receptor c-Kit as targets for inflammatory diseases
source: Eur J Pharmacol 533:327-40
year: 2006

UnificationXref1260
type: UnificationXref
id: REACT_160518
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_160518.1

UnificationXref8377
type: UnificationXref
id: 1806199
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1806199

Evidence86
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17637696
xref: http://identifiers.org/pubmed/19196711
xref: http://identifiers.org/pubmed/11242034
xref: http://identifiers.org/pubmed/11861597
comment: The mitogen activated protein kinase (MAPK) cascade, one of the most ancient and evolutionarily conserved signaling pathways, is involved in many processes of immune responses. The MAP kinases cascade transduces signals from the cell membrane to the nucleus in response to a wide range of stimuli (Chang and Karin, 2001; Johnson et al, 2002). There are three major groups of MAP kinases the extracellular signal-regulated protein kinases ERK1/2, the p38 MAP kinase and the c-Jun NH-terminal kinases JNK. ERK1 and ERK2 are activated in response to growth stimuli. Both JNKs and p38-MAPK are activated in response to a variety of cellular and environmental stresses. The MAP kinases are activated by dual phosphorylation of Thr and Tyr within the tripeptide motif Thr-Xaa-Tyr. The sequence of this tripeptide motif is different in each group of MAP kinases: ERK (Thr-Glu-Tyr); p38 (Thr-Gly-Tyr); and JNK (Thr-Pro-Tyr). MAPK activation is mediated by signal transduction in the conserved three-tiered kinase cascade: MAPKKKK (MAP4K or MKKKK or MAPKKK Kinase) activates the MAPKKK. The MAPKKKs then phosphorylates a dual-specificity protein kinase MAPKK, which in turn phosphorylates the MAPK. The dual specificity MAP kinase kinases (MAPKK or MKK) differ for each group of MAPK. The ERK MAP kinases are activated by the MKK1 and MKK2; the p38 MAP kinases are activated by MKK3, MKK4, and MKK6; and the JNK pathway is activated by MKK4 and MKK7. The ability of MAP kinase kinases (MKKs, or MEKs) to recognize their cognate MAPKs is facilitated by a short docking motif (the D-site) in the MKK N-terminus, which binds to a complementary region on the MAPK. MAPKs then recognize many of their targets using the same strategy, because many MAPK substrates also contain D-sites. The upstream signaling events in the TLR cascade that initiate and mediate the ERK signaling pathway remain unclear.

UnificationXref8376
type: UnificationXref
id: REACT_180641
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_180641.3

Evidence85
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17637696
xref: http://identifiers.org/pubmed/17158707
xref: http://identifiers.org/pubmed/16393692
xref: http://identifiers.org/pubmed/19767751
xref: http://identifiers.org/pubmed/12471242
comment: MAPKs are protein kinases that, once activated, phosphorylate their specific cytosolic or nuclear substrates at serine and/or threonine residues. Such phosphorylation events can either positively or negatively regulate substrate, and thus entire signaling cascade activity. The major cytosolic target of activated ERKs are RSKs (90 kDa Ribosomal protein S6 Kinase). Active RSKs translocates to the nucleus and phosphorylates such factors as c-Fos(on Ser362), SRF (Serum Response Factor) at Ser103, and CREB (Cyclic AMP Response Element-Binding protein) at Ser133. In the nucleus activated ERKs phosphorylate many other targets such as MSKs (Mitogen- and Stress-activated protein kinases), MNK (MAP interacting kinase) and Elk1 (on Serine383 and Serine389). ERK can directly phosphorylate CREB and also AP-1 components c-Jun and c-Fos. Another important target of ERK is NF-KappaB. Recent studies reveals that nuclear pore proteins are direct substrates for ERK (Kosako H et al, 2009). Other ERK nuclear targets include c-Myc, HSF1 (Heat-Shock Factor-1), STAT1/3 (Signal Transducer and Activator of Transcription-1/3), and many more transcription factors. Activated p38 MAPK is able to phosphorylate a variety of substrates, including transcription factors STAT1, p53, ATF2 (Activating transcription factor 2), MEF2 (Myocyte enhancer factor-2), protein kinases MSK1, MNK, MAPKAPK2/3, death/survival molecules (Bcl2, caspases), and cell cycle control factors (cyclin D1). JNK, once activated, phosphorylates a range of nuclear substrates, including transcription factors Jun, ATF, Elk1, p53, STAT1/3 and many other factors. JNK has also been shown to directly phosphorylate many nuclear hormone receptors. For example, peroxisome proliferator-activated receptor 1 (PPAR-1) and retinoic acid receptors RXR and RAR are substrates for JNK. Other JNK targets are heterogeneous nuclear ribonucleoprotein K (hnRNP-K) and the Pol I-specific transcription factor TIF-IA, which regulates ribosome synthesis. Oth…

UnificationXref8375
type: UnificationXref
id: 5616443
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616443

Evidence88
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15678101
xref: http://identifiers.org/pubmed/20937827
xref: http://identifiers.org/pubmed/11447294
xref: http://identifiers.org/pubmed/12839990
comment: CDK1-mediated phosphorylation of GORASP1 (GRASP65) enables GORASP1 to recruit PLK1 (Preisinger et al. 2005). PLK1 phosphorylates GORASP1 on serine residue S189 (Sengupta and Linstedt 2010). This serine residue is near the GORASP1 region involved in GORASP1 dimerization and oligomerization, a process underlying the stacking of cis-Golgi cisternae (Wang et al. 2003). The phosphorylation of S189 by PLK1 impairs Golgi cisternae stacking (tethering), contributing to Golgi unlinking and fragmentation in mitosis, probably by preventing formation of GORASP1 dimers and oligomers (Sutterlin et al. 2001, Sengupta and Linstedt, 2010). Two other potential phosphorylation sites that match PLK1 substrate consensus sequence exist in GORASP1, but their functional significance has not yet been examined (Sengupta and Linstedt, 2010).

UnificationXref8374
type: UnificationXref
id: REACT_180633
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_180633.3

Evidence87
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19112497
xref: http://identifiers.org/pubmed/19675569
xref: http://identifiers.org/pubmed/12609980
comment: In human, together with ubiquitin-conjugating E2-type enzymes UBC13 and UEV1A (also known as UBE2V1), TRAF6 catalyses Lys63-linked ubiquitination. It is believed that auto polyubiquitination and oligomerization of TRAF6 is followed by binding the ubiquitin receptors of TAB2 or TAB3 (TAK1 binding protein 2 and 3), which stimulates phosphorylation and activation of TGF beta-activated kinase 1(TAK1). TAK1 phosphorylates IKK alpha and IKK beta, which in turn phosphorylate NF-kB inhibitors - IkB and eventually results in IkB degradation and NF-kB translocation to the nucleus. Also TAK1 mediates JNK and p38 MAP kinases activation by phosphorylating MKK4/7 and MKK3/6 respectivly resulting in the activation of many transcription factors. The role of TRAF6 is somewhat controversial and probably cell type specific. TRAF6 autoubiquitination was found to be dispensable for TRAF6 function to activate TAK1 pathway. These findings are consistent with the new mechanism of TRAF6-mediated NF-kB activation that was suggested by Xia et al. (2009). TRAF6 generates unanchored Lys63-linked polyubiquitin chains that bind to the regulatory subunits of TAK1 (TAB2 or TAB3) and IKK(NEMO), leading to the activation of the kinases. Xia et al. (2009) demonstrated in vitro that unlike polyubiquitin chains covalently attached to TRAF6 or IRAK, TAB2 and NEMO-associated ubiquitin chains were found to be unanchored and susceptible to N-terminal ubiquitin cleavage. Only K63-linked polyubiquitin chains, but not monomeric ubiquitin, activated TAK1 in a dose-dependent manner. Optimal activation of the IKK complex was achieved using ubiquitin polymers containing both K48 and K63 linkages. Furthermore, the authors proposed that the TAK1 complexes might be brougt in close proximity by binding several TAB2/3 to a single polyubiquitin chain to facilitate TAK1 kinase trans-phosphorylation. Alternativly, the possibility that polyUb binding promotes allosteric activation of TAK1 complex should be considered (Wals…

UnificationXref8373
type: UnificationXref
id: 5616441
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616441

UnificationXref8372
type: UnificationXref
id: 5616439
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616439

Evidence89
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9458043
xref: http://identifiers.org/pubmed/15678101
xref: http://identifiers.org/pubmed/17182854
xref: http://identifiers.org/pubmed/18385516
xref: http://identifiers.org/pubmed/15576368
xref: http://identifiers.org/pubmed/20937827
xref: http://identifiers.org/pubmed/11447294
xref: http://identifiers.org/pubmed/11285137
xref: http://identifiers.org/pubmed/20083603
xref: http://identifiers.org/pubmed/12839990
xref: http://identifiers.org/pubmed/11739401
xref: http://identifiers.org/pubmed/15232108
xref: http://identifiers.org/pubmed/18434598
xref: http://identifiers.org/pubmed/12695496
xref: http://identifiers.org/pubmed/17431394
xref: http://identifiers.org/pubmed/16533948
xref: http://identifiers.org/pubmed/9753325
xref: http://identifiers.org/pubmed/12015985
xref: http://identifiers.org/pubmed/10679020
xref: http://identifiers.org/pubmed/11408587
comment: The pericentriolar stacks of Golgi cisternae undergo extensive fragmentation and reorganization in mitosis. In mammalian cells, Golgi apparatus consists of stacked cisternae that are connected by tubules to form a ribbon-like structure in the perinuclear region, in vicinity of the centrosome. Reorganization of the Golgi apparatus during cell division allows both daughter cells to inherit this organelle, and may play additional roles in the organization of the mitotic spindle. First changes in the structure of the Golgi apparatus likely start in G2 and are subtle, involving unlinking of the Golgi ribbon into separate stacks. These changes are required for the entry of mammalian cells into mitosis (Sutterlin et al. 2002). This initial unlinking of the Golgi ribbon depends on GRASP proteins and on CTBP1 (BARS) protein, which induces the cleavage of the tubular membranes connecting the stacks (Hidalgo Carcedo et al. 2004, Colanzi et al. 2007), but the exact mechanism is not known. Activation of MEK1/2 also contributes to unlinking of the Golgi ribbon in G2 (Feinstein and Linstedt 2007). From prophase to metaphase, Golgi cisternae undergo extensive fragmentation that is a consequence of unstacking of Golgi cisternae and cessation of transport through Golgi. At least three mitotic kinases, CDK1, PLK1 and MEK1, regulate these changes. CDK1 in complex with cyclin B phosphorylates GOLGA2 (GM130) and GORASP1 (GRASP65), constituents of a cis-Golgi membrane complex (Lowe et al. 1998, Preisinger et al. 2005). Phosphorylation of GOLGA2 prevents binding of USO1 (p115), a protein localizing to the membrane of ER (endoplasmic reticulum) to Golgi transport vesicles and cis-Golgi, thereby impairing fusion of these vesicles with cis-Golgi cisternae and stopping ER to Golgi transport (Lowe et al. 1998, Seeman et al. 2000, Moyer et al. 2001). Phosphorylation of GORASP1 by CDK1 enables further phosphorylation of GORASP1 by PLK1 (Sutterlin et al. 2001, Preisinger et al. 2005). Phosphorylat…

UnificationXref8371
type: UnificationXref
id: 5616437
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616437

Stoichiometry1709
type: Stoichiometry
physical entity: Protein1716
stoichiometric coefficient: 2.0

UnificationXref8370
type: UnificationXref
id: 5616438
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616438

Stoichiometry1707
type: Stoichiometry
physical entity: Protein1712
stoichiometric coefficient: 2.0

Stoichiometry1708
type: Stoichiometry
physical entity: Protein1715
stoichiometric coefficient: 2.0

Evidence80
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: Activated MEK phosphorylates and activates ERK.

Stoichiometry1705
type: Stoichiometry
physical entity: Protein1706
stoichiometric coefficient: 4.0

Stoichiometry1706
type: Stoichiometry
physical entity: SmallMolecule6
stoichiometric coefficient: 4.0

Evidence82
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16456541
comment: ERKs are inactivated by the protein phosphatase 2A (PP2A). The PP2A holoenzyme is a heterotrimer that consists of a core dimer, composed of a scaffold (A) and a catalytic (C) subunit that associates with a variety of regulatory (B) subunits. The B subunits have been divided into gene families named B (or PR55), B0 (or B56 or PR61) and B00 (or PR72). Each family comprises several members. B56 family members of PP2A in particular, increase ERK dephosphorylation, without affecting its activation by MEK. Induction of PP2A is involved in the extracellular signal-regulated kinase (ERK) signalling pathway, in which it provides a feedback control, as well as in a broad range of other cellular processes, including transcriptional regulation and control of the cell cycle.This diversity of functions is conferred by a diversity of regulatory subunits, the combination of which can give rise to over 50 different forms of PP2A. For example, five distinct mammalian genes encode members of the B56 family, called B56a, b, g, d and e, generating at least eight isoforms. Whether a specific holoenzyme dephosphorylates ERK and whether this activity is controlled during mitogenic stimulation is unknown.

Stoichiometry1703
type: Stoichiometry
physical entity: Protein1706
stoichiometric coefficient: 2.0

Evidence81
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: The MEF2 (Myocyte-specific enhancer factor 2) proteins constitute a family of transcription factors: MEF2A, MEF2B, MEF2C, and MEF2D. MEF2A and MEF2C are known substrates of ERK5, and their transactivating activity can be stimulated by ERK5 via direct phosphorylation. MEF2A and MEF2C are expressed in developing and adult brain including cortex and cerebellum.

Stoichiometry1704
type: Stoichiometry
physical entity: SmallMolecule6
stoichiometric coefficient: 2.0

http://identifiers.org/pubmed/11598006
type: PublicationXref
id: 11598006
author: Neupert, W
author: Diekert, K
author: Niggemeyer, B
author: Lill, R
author: Ahting, U
author: de Kruijff, B
author: de Kroon, AI
db: Pubmed
title: Apocytochrome c requires the TOM complex for translocation across the mitochondrial outer membrane
source: EMBO J 20:5626-35
year: 2001

UnificationXref8379
type: UnificationXref
id: 5616407
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616407

Evidence84
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: ERK/MAPK kinases have a number of targets within the nucleus, usually transcription factors or other kinases. The best known targets, ELK1, ETS1, ATF2, MITF, MAPKAPK2, MSK1, RSK1/2/3 and MEF2 are annotated here.

Stoichiometry1701
type: Stoichiometry
physical entity: SmallMolecule235
stoichiometric coefficient: 2.0

UnificationXref8378
type: UnificationXref
id: REACT_123880
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_123880.1

SequenceSite309
type: SequenceSite
position status: EQUAL
sequence position: 786

Evidence83
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/15115656
xref: http://identifiers.org/pubmed/17322878
comment: MAP Kinases are inactivated by a family of protein named MAP Kinase Phosphatases (MKPs). They act through dephosphorylation of threonine and/or tyrosine residues within the signature sequence -pTXpY- located in the activation loop of MAP kinases (pT=phosphothreonine and pY=phosphotyrosine). MKPs are divided into three major categories depending on their preference for dephosphorylating; tyrosine, serine/threonine and both the tyrosine and threonine (dual specificity phoshatases or DUSPs). The tyrosine-specific MKPs include PTP-SL, STEP and HePTP, serine/threonine-specific MKPs are PP2A and PP2C, and many DUSPs acting on MAPKs are known. Activated MAP kinases trigger activation of transcription of MKP genes. Therefore, MKPs provide a negative feedback regulatory mechanism on MAPK signaling, by inactivating MAPKs via dephosphorylation, in the cytoplasm and the nucleus. Some MKPs are more specific for ERKs, others for JNK or p38MAPK.

Stoichiometry1702
type: Stoichiometry
physical entity: Protein1705
stoichiometric coefficient: 2.0

UnificationXref9860
type: UnificationXref
id: REACT_232526
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_232526.1

SequenceSite318
type: SequenceSite
position status: EQUAL
sequence position: 2

Stoichiometry1700
type: Stoichiometry
physical entity: Protein1662
stoichiometric coefficient: 2.0

SequenceSite319
type: SequenceSite
position status: EQUAL
sequence position: 148

UnificationXref9862
type: UnificationXref
id: REACT_230520
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_230520.1

SequenceSite316
type: SequenceSite
position status: EQUAL
sequence position: 1

http://identifiers.org/pubmed/8163488
type: PublicationXref
id: 8163488
author: Schlossmann, J
author: Neupert, W
author: Pfanner, N
author: Dietmeier, K
db: Pubmed
title: Specific recognition of mitochondrial preproteins by the cytosolic domain of the import receptor MOM72
source: J Biol Chem 269:11893-901
year: 1994

UnificationXref9861
type: UnificationXref
id: 5615004
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5615004

SequenceSite317
type: SequenceSite
position status: EQUAL
sequence position: 165

SequenceSite314
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite315
type: SequenceSite
position status: EQUAL
sequence position: 165

SequenceSite312
type: SequenceSite
position status: EQUAL
sequence position: 2

SequenceSite313
type: SequenceSite
position status: EQUAL
sequence position: 203

UnificationXref9868
type: UnificationXref
id: 5613415
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613415

SequenceSite310
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref9867
type: UnificationXref
id: Q03028
db: UniProt

UnificationXref8380
type: UnificationXref
id: REACT_181450
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_181450.3

SequenceSite311
type: SequenceSite
position status: EQUAL
sequence position: 203

http://identifiers.org/pubmed/20188572
type: PublicationXref
id: 20188572
author: von Lintig, Johannes
author: Palczewski, Krzysztof
author: Kiser, Philip D
author: Golczak, Marcin
db: Pubmed
title: The biochemical and structural basis for trans-to-cis isomerization of retinoids in the chemistry of vision
source: Trends Biochem. Sci. 35:400-10
year: 2010

UnificationXref9869
type: UnificationXref
id: 5613416
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613416

UnificationXref9864
type: UnificationXref
id: REACT_5045
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_5045.1

UnificationXref9863
type: UnificationXref
id: 113577
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113577

UnificationXref9866
type: UnificationXref
id: 5613411
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613411

UnificationXref9865
type: UnificationXref
id: Q99297
db: UniProt

UnificationXref8386
type: UnificationXref
id: REACT_188968
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_188968.3

Evidence99
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17525332
xref: http://identifiers.org/pubmed/17356064
xref: http://identifiers.org/pubmed/9774278
xref: http://identifiers.org/pubmed/19915589
xref: http://identifiers.org/pubmed/7954811
xref: http://identifiers.org/pubmed/20703077
xref: http://identifiers.org/pubmed/17066080
xref: http://identifiers.org/pubmed/19608861
xref: http://identifiers.org/pubmed/9288743
xref: http://identifiers.org/pubmed/19481522
xref: http://identifiers.org/pubmed/15572404
xref: http://identifiers.org/pubmed/15146063
xref: http://identifiers.org/pubmed/9160743
xref: http://identifiers.org/pubmed/14607834
xref: http://identifiers.org/pubmed/11136719
xref: http://identifiers.org/pubmed/18977199
comment: The condensin I complex is evolutionarily conserved and consists of five subunits: two SMC (structural maintenance of chromosomes) family subunits, SMC2 and SMC4, and three non-SMC subunits, NCAPD2, NCAPH and NCAPG. The stoichiometry of the complex is 1:1:1:1:1 (Hirano and Mitchinson 1994, Hirano et al. 1997, Kimura et al. 2001). SMC2 and SMC4 subunits, shared between condensin I and condensin II, are DNA-dependent ATPases, and condensins are able to introduce positive supercoils into DNA in an ATP-dependent manner (Kimura and Hirano 1997). Protein levels of condensin subunits are constant during the cell cycle, however condensins are enriched on mitotic chromosomes. Four of the five subunits, SMC4, NCAPD2, NCAPG and NCAPH, are phosphorylated in both mitotic and interphase HeLa cells, but on different sites (Takemoto et al. 2004). CDK1 (CDC2) in complex with CCNB (cyclin B) phosphorylates NCAPD2, NCAPG and NCAPH in mitosis (Kimura et al. 1998, Kimura et al. 2001, Takemoto et al. 2006, Murphy et al. 2008), but other mitotic kinases, such as PLK1 (St-Pierre et al. 2009), and other post-translational modifications, such as acetylation, may also be involved (reviewed by Bazile et al. 2010). Global proteomic analysis of human cell lines has identified N6-acetylation of lysine residues in condensin subunits SMC2, SMC4 and NCAPH (Choudhary et al. 2009). Another high throughput proteomic study showed that condensin I subunits NCAPD2 and NCAPH are phosphorylated upon DNA damage, probably by ATM or ATR kinase (Matsuoka et al. 2007). As condensin I is cytosolic, it gains access to chromosomes only after the nuclear envelope breakdown at the start of prometaphase (Ono et al. 2004). Condensin I, activated by CDK1-mediated phosphorylation, promotes hypercondensation of chromosomes that were condensed in prophase through the action of condensin II (Hirota et al. 2004). AURKB may also regulate association of condensin I complex with chromatin (Lipp et al. 2007). Protein phosphatase…

UnificationXref8385
type: UnificationXref
id: 5618615
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5618615

Evidence98
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/9774278
xref: http://identifiers.org/pubmed/17066080
xref: http://identifiers.org/pubmed/11136719
xref: http://identifiers.org/pubmed/18977199
comment: CDK1 (CDC2) in complex with CCNB (cyclin B) phosphorylates condensin I subunits NCAPD2, NCAPG and NCAPH in mitosis (Kimura et al. 2001, Takemoto et al. 2006), but other mitotic kinases may also be involved. CDK1 phosphorylation sites in NCAPH have not been established. NCAPD2 threonine residues T1339, T1384 and T1389 are inferred to be phosphorylated by CDK1 based on homologues sites in Xenopus laevis Ncapd2 (Kimura et al. 1998). NCAPG threonine residues T308 and T332 are phosphorylated by CDK1 in vitro and functionally important. The functional importance of threonine T931, also phosphorylated by CDK1 in vitro, has not been demonstrated (Murphy et al. 2008). Phosphorylation by CDK1 is required for mitotic activation of condensin I and promotes chromosomal binding, introduction of positive supercoils into DNA, and chromatin condensation (Kimura et al. 1998, Kimura et al. 2001, Takemoto et al. 2006).

UnificationXref8388
type: UnificationXref
id: REACT_125283
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_125283.1

Evidence97
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17066080
comment: Inhibitory phosphate groups that were added to condensin I subunits by CK2 during interphase have to be removed for full mitotic activation of condensin I (Takemoto et al. 2006). The responsible phosphatase has not been identified.

http://identifiers.org/pubmed/20357282
type: PublicationXref
id: 20357282
author: Moslemi, Ali-Reza
author: Nilsson, Johanna
author: Andersson, Bert
author: Lindberg, Christopher
author: Tajsharghi, Homa
author: Oldfors, A
db: Pubmed
title: Glycogenin-1 deficiency and inactivated priming of glycogen synthesis
source: N. Engl. J. Med. 362:1203-10
year: 2010

UnificationXref8387
type: UnificationXref
id: 1806198
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1806198

Evidence96
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17066080
xref: http://identifiers.org/pubmed/14607834
comment: Protein levels of condensin subunits are constant during the cell cycle. Four subunits, SMC4, NCAPD2, NCAPG and NCAPH, are phosphorylated in interphase cells (Takemoto et al. 2004) by CK2 i.e. casein kinase II (Takemoto et al. 2006). Except for the phosphorylation of NCAPH subunit on serine residue S570, CK2 phosphorylation sites in condensin I subunits have not been identified. Phosphorylation by CK2 inhibits condensin I-mediated introduction of positive supercoils into DNA and chromatin condensation. Mitotic activation of condensin I involves removal of phosphate groups added by CK2 (Takemoto et al. 2006), but the responsible phosphatase has not been identified.

UnificationXref8382
type: UnificationXref
id: REACT_122226
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_122226.1

UnificationXref8381
type: UnificationXref
id: 1806180
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1806180

UnificationXref8384
type: UnificationXref
id: REACT_181451
db: Reactome
id version: 3
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_181451.3

UnificationXref8383
type: UnificationXref
id: 5616409
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5616409

Stoichiometry1716
type: Stoichiometry
physical entity: Protein1726
stoichiometric coefficient: 1.0

Evidence91
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/17158099
xref: http://identifiers.org/pubmed/18694939
comment: Lipin proteins LPIN1, 2, and 3, associated with the nuclear envelope, can each catalyze the hydrolysis of phosphatidate to yield 1,2-diacyl-glycerol and orthophosphate. The activities of LPIN1 and LPIN2 have been established experimentally (Grimsey et al. 2008); that of LPIN3 is inferred from its structural similarities both to its human paralogues and to its mouse ortholog (Donkor et al. 2007).

Stoichiometry1717
type: Stoichiometry
physical entity: SmallMolecule436
stoichiometric coefficient: 1.0

Evidence90
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/21081492
xref: http://identifiers.org/pubmed/18694939
xref: http://identifiers.org/pubmed/20876142
comment: Lipins (LPIN1, LPIN2, LPIN3) possess several proline-directed phosphorylation sites that can be phosphorylated by CDK1 (Grimsey et al. 2008), including S106. Serine S106 in lipins is a preferred target for dephosphorylation by the evolutionarilly conserved CTDNEP1:CNEP1R1 complex (ortholog of yeast NEM1:SPO7 complex). Lipin phosphorylation regulates lipin localization, with phosphorylated lipins being soluble and dephosphorylated lipins being membrane-bound. The yeast ortholog of CDK1, CDC28, as well as human CDK1 can phosphorylate yeast lipin PAH1, inducing its dissociation from the nuclear envelope and endoplasmic reticulum membrane (Choi et al. 2011).

Stoichiometry1718
type: Stoichiometry
physical entity: Protein1727
stoichiometric coefficient: 1.0

Stoichiometry1719
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 1.0

Stoichiometry1712
type: Stoichiometry
physical entity: Protein1721
stoichiometric coefficient: 2.0

Evidence95
type: Evidence
evidence code: EvidenceCodeVocabulary1
comment: During prophase, the chromatin in the nucleus condenses, and the nucleolus disappears. Centrioles begin moving to the opposite poles or sides of the cell. Some of the fibers that extend from the centromeres cross the cell to form the mitotic spindle.

UnificationXref8389
type: UnificationXref
id: 1806289
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1806289

Stoichiometry1713
type: Stoichiometry
physical entity: SmallMolecule432
stoichiometric coefficient: 1.0

Evidence94
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/19234477
comment: The nuclear envelope breakdown (NEBD) happens in late prophase of mitosis and involves disassembly of the nuclear pore complex, depolymerization of the nuclear lamina, and clearance of nuclear envelope from chromatin. NEBD allows mitotic spindle microtubules to access condensed chromosomes at kinetochores and enables nuclear division and segregation of genetic material to two daughter cells. For a recent review, please refer to Guttinger et al. 2009.

http://identifiers.org/pubmed/22952392
type: PublicationXref
id: 22952392
author: Nusse, Roel
author: Willert, Karl
db: Pubmed
title: Wnt proteins
source: Cold Spring Harb Perspect Biol 4:a007864
year: 2012

Stoichiometry1714
type: Stoichiometry
physical entity: Protein1726
stoichiometric coefficient: 1.0

Evidence93
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/23212477
xref: http://identifiers.org/pubmed/8463284
xref: http://identifiers.org/pubmed/19494125
xref: http://identifiers.org/pubmed/2188730
xref: http://identifiers.org/pubmed/22986494
xref: http://identifiers.org/pubmed/19494126
xref: http://identifiers.org/pubmed/2188731
xref: http://identifiers.org/pubmed/2344612
xref: http://identifiers.org/pubmed/21413788
xref: http://identifiers.org/pubmed/8034666
xref: http://identifiers.org/pubmed/22134922
comment: The nuclear envelope breakdown in mitotic prophase involves depolymerisation of lamin filaments, the main constituents of the nuclear lamina. The nuclear lamina is located at the nuclear face of the inner nuclear membrane and plays and important role in the structure and function of the nuclear envelope (reviewed by Burke and Stewart 2012). Depolymerisation of lamin filaments, which consist of lamin homodimers associated through electrostatic interactions in head-to-tail molecular strings, is triggered by phosphorylation of lamins. While CDK1 phosphorylates the N-termini of lamins (Heald and McKeon 1990, Peter et al. 1990, Ward and Kirschner 1990, Mall et al. 2012), PKCs (PRKCA and PRKCB) phosphorylate the C-termini of lamins (Hocevar et al. 1993, Goss et al. 1994, Mall et al. 2012). PKCs are activated by lipid-mediated signaling, where lipins, activated by CTDNEP1:CNEP1R1 serine/threonine protein phosphatase complex, catalyze the formation of DAG (Gorjanacz et al. 2009, Golden et al. 2009, Wu et al. 2011, Han et al. 2012, Mall et al. 2012).

Stoichiometry1715
type: Stoichiometry
physical entity: SmallMolecule434
stoichiometric coefficient: 1.0

Evidence92
type: Evidence
evidence code: EvidenceCodeVocabulary1
xref: http://identifiers.org/pubmed/16861033
xref: http://identifiers.org/pubmed/22986494
comment: PKC contains an N-terminal C2 like domain, a pseudosubstrate (PS), DAG binding (C1) domain and a C-terminal kinase domain. The PS sequence resembles an ideal substrate with the exception that it contains an alanine residue instead of a substrate serine residue, is bound to the kinase domain in the resting state. As a result, PKC is maintained in a closed inactive state, which is inaccessible to cellular substrates (Colon-Gonzalez & Kazanietz 2006). Diacylglycerol (DAG) produced by activated lipins (LPIN1, LPIN2, LPIN3) leads to the activation of PKC (PRKCA and PRKCB) and their translocation from the nucleoplasm to the nuclear envelope where they can phosphorylate lamins (Mall et al. 2012). PKCs are tethered to the membrane through DAG binding to the C1 domain and this confers a high-affinity interaction between PKC and the membrane. This leads to a massive conformational change that releases the PS domain from the catalytic site and the system becomes both competent and accessible (Colon-Gonzalez & Kazanietz 2006).

UnificationXref9873
type: UnificationXref
id: 70955
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=70955

SequenceSite305
type: SequenceSite
position status: EQUAL
sequence position: 953

UnificationXref9872
type: UnificationXref
id: CHEBI:15524
db: ChEBI

SequenceSite306
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref9871
type: UnificationXref
id: REACT_215044
db: Reactome
id version: 2
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_215044.2

SequenceSite307
type: SequenceSite
position status: EQUAL
sequence position: 908

Stoichiometry1711
type: Stoichiometry
physical entity: SmallMolecule425
stoichiometric coefficient: 2.0

UnificationXref9870
type: UnificationXref
id: 5613418
db: Reactome Database ID Release 49
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5613418

SequenceSite308
type: SequenceSite
position status: EQUAL
sequence position: 1

Stoichiometry1710
type: Stoichiometry
physical entity: SmallMolecule162
stoichiometric coefficient: 2.0