Stoichiometry10
type: Stoichiometry
physical entity: Tbl1
stoichiometric coefficient: 1.0

Tbl1
type: Protein
data source: Reactome
member physical entity: Transducin beta-like 1X-related protein 1
member physical entity: F-box-like/WD repeat-containing protein TBL1X
xref: UnificationXref19
xref: UnificationXref18
cellular location: nucleoplasm
comment: Reactome DB_ID: 2064259
comment: Converted from EntitySet in Reactome

SUH_HUMAN
type: Protein
entity reference: RBPSUH
data source: Reactome
name: Recombining binding protein suppressor of hairless
xref: UnificationXref7
xref: UnificationXref8
feature: FragmentFeature2
cellular location: nucleoplasm
comment: Reactome DB_ID: 3008668
display name: RBPJ

Transducin beta-like 1X-related protein 1
type: Protein
entity reference: Ira1
data source: Reactome
name: F-box-like/WD repeat-containing protein TBL1XR1
name: Tbl1xr1
xref: UnificationXref17
xref: UnificationXref16
feature: FragmentFeature4
cellular location: nucleoplasm
comment: Reactome DB_ID: 2064254
display name: Tblr1

F-box-like/WD repeat-containing protein TBL1X
type: Protein
entity reference: Tbl1x
data source: Reactome
name: Tbl1x
name: Transducin beta-like protein 1X
xref: UnificationXref14
xref: UnificationXref13
feature: FragmentFeature3
cellular location: nucleoplasm
comment: Reactome DB_ID: 2064253
display name: Tbl1

Nuclear receptor corepressor 1
type: Protein
entity reference: KIAA1047
data source: Reactome
name: NCOR1_HUMAN
xref: UnificationXref22
xref: UnificationXref21
feature: FragmentFeature5
cellular location: nucleoplasm
comment: Reactome DB_ID: 442501
display name: NCOR1

NCOR corepressor protein
type: Protein
data source: Reactome
member physical entity: Nuclear receptor corepressor 1
member physical entity: Nuclear receptor corepressor 2
xref: UnificationXref27
xref: UnificationXref26
cellular location: nucleoplasm
comment: Converted from EntitySet in Reactome
comment: Reactome DB_ID: 349716
display name: NCOR

SKIP
type: Protein
data source: Reactome
member physical entity: SNW domain-containing protein
xref: UnificationXref31
xref: UnificationXref32
cellular location: nucleoplasm
comment: Reactome DB_ID: 212438
comment: Converted from EntitySet in Reactome
display name: SNW

Stoichiometry11
type: Stoichiometry
physical entity: NCOR corepressor protein
stoichiometric coefficient: 1.0

Nuclear receptor corepressor 2
type: Protein
entity reference: CTG26
data source: Reactome
name: NCOR2_HUMAN
xref: UnificationXref25
xref: UnificationXref24
feature: FragmentFeature6
cellular location: nucleoplasm
comment: Reactome DB_ID: 442469
display name: NCOR2

Tbl1x
type: ProteinReference
name: Tbl1
name: UniProt:Q9QXE7 Tbl1x
xref: UnificationXref12
comment: TISSUE SPECIFICITY Expressed in the cochlea.SIMILARITY Belongs to the WD repeat EBI family.SIMILARITY Contains 1 F-box-like domain.SIMILARITY Contains 1 LisH domain.SIMILARITY Contains 8 WD repeats.
organism: Mus musculus

Homo sapiens
type: BioSource
xref: UnificationXref2

http://identifiers.org/pubmed/9694793
type: PublicationXref
id: 9694793
author: Kadesch, T
author: Downes, M
author: Kao, HY
author: Evans, RM
author: Ordentlich, P
author: Kintner, CR
author: Tang, Z
author: Koyano-Nakagawa, N
db: Pubmed
title: A histone deacetylase corepressor complex regulates the Notch signal transduction pathway
source: Genes Dev 12:2269-77
year: 1998

NICD1:RBPJ:SNW1
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry6
component stoichiometry: Stoichiometry7
component stoichiometry: Stoichiometry8
component: NICD 1 fragment
component: SUH_HUMAN
component: SNW domain-containing protein
xref: UnificationXref35
xref: UnificationXref36
cellular location: nucleoplasm
comment: Reactome DB_ID: 1604460

CSL NCOR co-repressor complex
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry2
component stoichiometry: Stoichiometry3
component stoichiometry: Stoichiometry1
component stoichiometry: Stoichiometry5
component stoichiometry: Stoichiometry4
component: HDAC1
component: NCOR corepressor protein
component: Tbl1
component: SKIP
component: SUH_HUMAN
xref: UnificationXref33
xref: UnificationXref34
cellular location: nucleoplasm
comment: Reactome DB_ID: 2064263

NCOR:HDAC1:Tbl1
type: Complex
data source: Reactome
component stoichiometry: Stoichiometry11
component stoichiometry: Stoichiometry10
component stoichiometry: Stoichiometry9
component: HDAC1
component: NCOR corepressor protein
component: Tbl1
xref: UnificationXref38
xref: UnificationXref37
cellular location: nucleoplasm
comment: Reactome DB_ID: 2064261

http://identifiers.org/pubmed/14980219
type: PublicationXref
id: 14980219
author: Glass, CK
author: Rose, DW
author: Aggarwal, A
author: Perissi, V
author: Rosenfeld, MG
db: Pubmed
title: A corepressor/coactivator exchange complex required for transcriptional activation by nuclear receptors and other regulated transcription factors
source: Cell 116:511-26
year: 2004

CTG26
type: ProteinReference
name: UniProt:Q9Y618 NCOR2
name: NCOR2
xref: UnificationXref23
comment: FUNCTION Transcriptional corepressor of NR4A2/NURR1 and acts through histone deacetylases (HDACs) to keep promoters of NR4A2/NURR1 target genes in a repressed deacetylated state (By similarity). Mediates the transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access of the basal transcription. Isoform 1 and isoform 5 have different affinities for different nuclear receptors.SUBUNIT Interacts with BCL6, HDAC7 and C1D. Interacts with NR4A2; this interaction increases in the absence of PITX3 (By similarity). Forms a large corepressor complex that contains SIN3A/B and histone deacetylases HDAC1 and HDAC2. This complex associates with the thyroid (TR) and the retinoid acid receptors (RAR) in the absence of ligand, and may stabilize their interaction with TFIIB. Interacts directly with RARA in the absence of ligand; the interaction represses RARA activity. Interacts (isoform SRMT) with HDAC10. Interacts with MINT. Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2. Interacts with CBFA2T3 and ATXN1L. Interacts with RARB; the interaction is weak and does not repress RARB transactivational activity.TISSUE SPECIFICITY Ubiquitous. High levels of expression are detected in lung, spleen and brain.INDUCTION Regulated during cell cycle progression.DOMAIN The N-terminal region contains repression functions that are divided into three independent repression domains (RD1, RD2 and RD3). The C-terminal region contains the nuclear receptor-interacting domains that are divided in two separate interaction domains (ID1 and ID2).DOMAIN The two interaction domains (ID) contain a conserved sequence referred to as the CORNR box. This motif is required and sufficient to permit binding to unligated TR and RARS. Sequences flanking the CORNR box determine nuclear hormone receptor specificity.SIMILARITY Belongs to the N-CoR nuclear receptor corepressors family.SIMILARITY Con…
organism: Homo sapiens

SKIIP
type: ProteinReference
name: SNW1
name: UniProt:Q13573 SNW1
name: SKIP
xref: UnificationXref28
comment: FUNCTION Involved in transcriptional regulation. Modulates TGF-beta-mediated transcription via association with SMAD proteins, MYOD1-mediated transcription via association with PABPN1, RB1-mediated transcriptional repression, and retinoid-X receptor (RXR)- and vitamin D receptor (VDR)-dependent gene transcription in a cell line-specific manner probably involving coactivators NCOA1 and GRIP1. Is involved in NOTCH1-mediated transcriptional activation. Binds to multimerized forms of Notch intracellular domain (NICD) and is proposed to recruit transcriptional coactivators such as MAML1 to form an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ to form a transcriptional activation complex by releasing SNW1 and redundant NOTCH1 NICD. Proposed to be involved in transcriptional activation by EBV EBNA2 of CBF-1/RBPJ-repressed promoters. Is recruited by HIV-1 Tat to Tat:P-TEFb:TAR RNA complexes and is involved in Tat transcription by recruitment of MYC, MEN1 and TRRAP to the HIV promoter. Functions as a splicing factor in pre-mRNA splicing. Is required in the specific splicing of CDKN1A pre-mRNA; the function probbaly involves the recruitment of U2AF2 to the mRNA. Is proposed to recruit PPIL1 to the spliceosome. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA.SUBUNIT Interacts SKI, SMAD2,SMAD3, RBPJ, RB1, PABPN1, MAGEA1, SIRT1, FOXN3, U2AF2, PPIL1, DAXX and ATP1B4. Interacts with VDR and RXRA; preferentially associates with VDR:RXRA heterodimers. Interacts with NCOR2 and EBV EBNA2; NCOR2 and EBV EBNA2 compete for interaction with SNW1. Interacts with MAML1. Interacts with NOTCH1 NICD; the interaction involves multimerized NOTCH1 NICD. Forms a complex with NOTCH1 NICD and MAML1; the association is dissociated by RBPJ. Identified in the spliceosome C complex. Associates with U4/U6-U5 tri-small nuclear ribonucleoproteins (U4/U6-U5 tri-snRNPs). Associates …
organism: Homo sapiens

nucleoplasm
type: CellularLocationVocabulary
xref: UnificationXref1

KIAA1047
type: ProteinReference
name: UniProt:O75376 NCOR1
name: NCOR1
xref: UnificationXref20
comment: FUNCTION Mediates transcriptional repression by certain nuclear receptors. Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors.SUBUNIT Interacts with C1D, SIAH2, HDAC7, SAP30, SIN3A and SIN3B (By similarity). Forms a large corepressor complex that contains. SIN3A/B and histone deacetylases HDAC1 and HDAC2. This complex associates with the thyroid (TR) and the retinoid acid receptors (RAR) in the absence of ligand. Interacts directly with RARA; the interaction is faciliated with RARA trimethylation. Interacts with DACH1. Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1XR1, CORO2A and GPS2. Interacts with TRIM28 and KDM3A. Interacts with ZBTB33; the interaction serves to recruit the N-CoR complex to promoter regions containing methylated CpG dinucleotides. Interacts with HDAC9 (via its catalytic domain). Interacts with CBFA2T3 and HEXIM1. Interacts (via the RRFD1 domain) with BAZ1A (via its N-terminal); the interaction corepresses a number of NCOR1-regulated genes.DOMAIN The N-terminal region contains three independent domains that are capable of mediating transcriptional repression (RD1, RD2 and RD3).SIMILARITY Belongs to the N-CoR nuclear receptor corepressors family.SIMILARITY Contains 2 SANT domains.
organism: Homo sapiens

Mus musculus
type: BioSource
xref: UnificationXref11

UnificationXref5
type: UnificationXref
id: REACT_2989
db: Reactome
id version: 6
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_2989.6

UnificationXref6
type: UnificationXref
id: Q06330
db: UniProt

UnificationXref3
type: UnificationXref
id: P46531
db: UniProt

UnificationXref4
type: UnificationXref
id: 157939
db: Reactome Database ID Release 45
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=157939

UnificationXref1
type: UnificationXref
id: GO:0005654
db: GENE ONTOLOGY

UnificationXref2
type: UnificationXref
id: 9606
db: NCBI Taxonomy

NICD 1 fragment
type: Protein
entity reference: NOTCH1
data source: Reactome
name: NOTCH1 intracellular domain
name: NOTCH1(1754-2555)
name: N1ICD
xref: UnificationXref5
xref: UnificationXref4
feature: FragmentFeature1
cellular location: nucleoplasm
comment: Reactome DB_ID: 157939
display name: NICD1

SequenceSite14
type: SequenceSite
position status: EQUAL
sequence position: 536

UnificationXref40
type: UnificationXref
id: REACT_118684
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_118684.2

UnificationXref9
type: UnificationXref
id: 2064257
db: Reactome Database ID Release 45
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2064257

SequenceSite11
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite9
type: SequenceSite
position status: EQUAL
sequence position: 1

SequenceSite10
type: SequenceSite
position status: EQUAL
sequence position: 2440

UnificationXref7
type: UnificationXref
id: 3008668
db: Reactome Database ID Release 45
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3008668

SequenceSite13
type: SequenceSite
position status: EQUAL
sequence position: 2

UnificationXref8
type: UnificationXref
id: REACT_160396
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_160396.2

SequenceSite12
type: SequenceSite
position status: EQUAL
sequence position: 2525

UnificationXref32
type: UnificationXref
id: REACT_15167
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_15167.2

UnificationXref33
type: UnificationXref
id: 2064263
db: Reactome Database ID Release 45
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2064263

UnificationXref30
type: UnificationXref
id: REACT_15097
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_15097.2

UnificationXref31
type: UnificationXref
id: 212438
db: Reactome Database ID Release 45
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=212438

NOTCH1
type: ProteinReference
name: UniProt:P46531 NOTCH1
name: TAN1
xref: UnificationXref3
comment: SUBUNIT Heterodimer of a C-terminal fragment N(TM) and an N-terminal fragment N(EC) which are probably linked by disulfide bonds. Interacts with DNER, DTX1, DTX2 and RBPJ/RBPSUH. Also interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH1. Notch 1 intracellular domain interacts with SNW1; the interaction involves multimerized NOTCH1 NICD and is implicated in a formation of an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ. The activated membrane-bound form interacts with AAK1 which promotes NOTCH1 stabilization. Forms a trimeric complex with FBXW7 and SGK1. Interacts with HIF1AN. HIF1AN negatively regulates the function of notch intracellular domain (NICD), accelerating myogenic differentiation (By similarity). Interacts (via NICD) with SNAI1 (via zinc fingers); the interaction induces SNAI1 degradation via MDM2-mediated ubiquitination and inhibits SNAI1-induced cell invasion. Interacts (via NICD) with MDM2A.TISSUE SPECIFICITY In fetal tissues most abundant in spleen, brain stem and lung. Also present in most adult tissues where it is found mainly in lymphoid tissues.PTM O-glycosylated on the EGF-like domains. Contains both O-linked fucose and O-linked glucose.PTM Ubiquitinated; undergoes 'Lys-29'-linked polyubiquitination catalyzed by ITCH. Monoubiquitination at Lys-1759 is required for activation by gamma-secretase cleavage, it promotes interaction with AAK1, which stabilizes it. Deubiquitination by EIF3F is necessary for nuclear import of activated Notch.DISEASE Aortic valve disease 1 (AOVD1) [MIM:109730]: A common defect in the aortic valve in which two rather than three leaflets are present. It is often associated with aortic valve calcification, stenosis and insufficiency. In extreme cases, the blood flow may be so restricted that the left ventricle fails to grow, resulting in hypoplastic left heart syndrome. Note=The disease is caused by mutations affecting the gene represented in this entry.S…
organism: Homo sapiens

Stoichiometry1
type: Stoichiometry
physical entity: SUH_HUMAN
stoichiometric coefficient: 1.0

Ira1
type: ProteinReference
name: Tblr1
name: Tbl1xr1
name: UniProt:Q8BHJ5 Tbl1xr1
xref: UnificationXref15
comment: SIMILARITY Belongs to the WD repeat EBI family.SIMILARITY Contains 1 F-box-like domain.SIMILARITY Contains 1 LisH domain.SIMILARITY Contains 8 WD repeats.
organism: Mus musculus

Stoichiometry3
type: Stoichiometry
physical entity: Tbl1
stoichiometric coefficient: 1.0

Stoichiometry2
type: Stoichiometry
physical entity: HDAC1
stoichiometric coefficient: 1.0

UnificationXref37
type: UnificationXref
id: 2064261
db: Reactome Database ID Release 45
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2064261

Stoichiometry5
type: Stoichiometry
physical entity: SKIP
stoichiometric coefficient: 1.0

Stoichiometry4
type: Stoichiometry
physical entity: NCOR corepressor protein
stoichiometric coefficient: 1.0

UnificationXref36
type: UnificationXref
id: REACT_119914
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119914.1

Stoichiometry7
type: Stoichiometry
physical entity: SUH_HUMAN
stoichiometric coefficient: 1.0

UnificationXref35
type: UnificationXref
id: 1604460
db: Reactome Database ID Release 45
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1604460

UnificationXref34
type: UnificationXref
id: REACT_119687
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119687.1

Stoichiometry6
type: Stoichiometry
physical entity: NICD 1 fragment
stoichiometric coefficient: 1.0

Stoichiometry9
type: Stoichiometry
physical entity: HDAC1
stoichiometric coefficient: 1.0

Stoichiometry8
type: Stoichiometry
physical entity: SNW domain-containing protein
stoichiometric coefficient: 1.0

UnificationXref39
type: UnificationXref
id: 2064264
db: Reactome Database ID Release 45
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2064264

UnificationXref38
type: UnificationXref
id: REACT_120185
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_120185.1

UnificationXref20
type: UnificationXref
id: O75376
db: UniProt

UnificationXref21
type: UnificationXref
id: 442501
db: Reactome Database ID Release 45
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=442501

UnificationXref22
type: UnificationXref
id: REACT_27555
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_27555.2

http://identifiers.org/pubmed/18374649
type: PublicationXref
id: 18374649
author: Zhang, J
author: Scafoglio, C
author: Glass, CK
author: Rose, DW
author: Perissi, V
author: Ohgi, KA
author: Rosenfeld, MG
db: Pubmed
title: TBL1 and TBLR1 phosphorylation on regulated gene promoters overcomes dual CtBP and NCoR/SMRT transcriptional repression checkpoints
source: Mol Cell 29:755-66
year: 2008

Reactome
type: Provenance
comment: http://www.reactome.org

SequenceSite6
type: SequenceSite
position status: EQUAL
sequence position: 527

UnificationXref24
type: UnificationXref
id: 442469
db: Reactome Database ID Release 45
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=442469

SequenceSite5
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref23
type: UnificationXref
id: Q9Y618
db: UniProt

SequenceSite8
type: SequenceSite
position status: EQUAL
sequence position: 514

UnificationXref26
type: UnificationXref
id: 349716
db: Reactome Database ID Release 45
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=349716

SequenceSite7
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref25
type: UnificationXref
id: REACT_27826
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_27826.2

SequenceSite2
type: SequenceSite
position status: EQUAL
sequence position: 2555

UnificationXref28
type: UnificationXref
id: Q13573
db: UniProt

SequenceSite1
type: SequenceSite
position status: EQUAL
sequence position: 1754

UnificationXref27
type: UnificationXref
id: REACT_119825
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_119825.2

SequenceSite4
type: SequenceSite
position status: EQUAL
sequence position: 500

SequenceSite3
type: SequenceSite
position status: EQUAL
sequence position: 1

UnificationXref29
type: UnificationXref
id: 351663
db: Reactome Database ID Release 45
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351663

UnificationXref10
type: UnificationXref
id: REACT_120286
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_120286.1

UnificationXref11
type: UnificationXref
id: 10090
db: NCBI Taxonomy

HDAC1
type: PhysicalEntity
data source: Reactome
xref: UnificationXref10
xref: UnificationXref9
cellular location: nucleoplasm
comment: Reactome DB_ID: 2064257

http://identifiers.org/pubmed/10713164
type: PublicationXref
id: 10713164
author: Weinmaster, G
author: Zhou, S
author: Hayward, SD
author: Fujimuro, M
author: Hsieh, JJ
author: Miyamoto, A
author: Chen, L
db: Pubmed
title: SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function
source: Mol Cell Biol 20:2400-10
year: 2000

UnificationXref19
type: UnificationXref
id: REACT_119321
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119321.1

UnificationXref18
type: UnificationXref
id: 2064259
db: Reactome Database ID Release 45
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2064259

UnificationXref17
type: UnificationXref
id: REACT_118965
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_118965.1

UnificationXref16
type: UnificationXref
id: 2064254
db: Reactome Database ID Release 45
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2064254

UnificationXref15
type: UnificationXref
id: Q8BHJ5
db: UniProt

UnificationXref14
type: UnificationXref
id: REACT_120209
db: Reactome
id version: 1
comment: Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_120209.1

UnificationXref13
type: UnificationXref
id: 2064253
db: Reactome Database ID Release 45
comment: Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2064253

UnificationXref12
type: UnificationXref
id: Q9QXE7
db: UniProt

NICD1 displaces NCOR co-repressor complex from CSL
type: BiochemicalReaction
data source: Reactome
xref: http://identifiers.org/pubmed/9694793
xref: UnificationXref40
xref: UnificationXref39
xref: http://identifiers.org/pubmed/18374649
xref: http://identifiers.org/pubmed/14980219
xref: http://identifiers.org/pubmed/10713164
left: NICD 1 fragment
left: CSL NCOR co-repressor complex
comment: Edited: Orlic-Milacic, M, 2012-02-10
comment: Authored: Egan, SE, Orlic-Milacic, M, 2011-11-14
comment: Reviewed: Haw, R, 2012-02-06
comment: Edited: D'Eustachio, P, 2012-02-06
comment: Interaction of RBPJ (CSL) with NCOR2 (SMRT) was initially discovered in a yeast two-hybrid assay, using human recombinant proteins, and was confirmed in mammalian cells by co-immunoprecipitation of exogenously expressed human RBPJ and NCOR2 from the mouse fibroblast cell line NIH 3T3, as well as by a mammalian two-hybrid assay. These experiments also established, using a RBPJ repression domain mutant, that the repression domain was necessary for interaction with NCOR2 (Kao et al. 1998). Using a mammalian two-hybrid assay, it was found that RBPJ also interacts with NCOR1 in a repression domain dependent way. Over-expression of NCOR2 inhibits transcriptional activity of TAN-1, a gain-of-function NOTCH1 mutant found in T-ALL, through disrupting the interaction of TAN-1 with RBPJ (Kao et al. 1998). NOTCH target genes were found to be de-repressed when cells were treated with TSA (trichostatin A), an inhibitor of HDAC1. HDAC1, known to interact with NCOR2, was found to interact with RBPJ: exogenously expressed human RBPJ co-immunoprecipitated endogenous mouse HDAC1 from CV-1 cell line, derived by from kidney cells of the vervet monkey (also known as the African green monkey, Cercopithecus aethiops or Chlorobus aethiops). The interaction of HDAC1 with RBPJ was dependent on the presence of repression domain (Kao et al. 1998). The recombinant human protein SNW1 (SKIP) was shown to interact with recombinant human RBPJ as part of a transcriptional repression complex, but stays bound to recombinant mouse NICD1 and RBPJ and aids NOTCH-mediated transcription once the NCOR co-repression complex is displaced by NICD1 (Zhou et al. 2000). Mouse Tbl1x and Tbl1xr1 were also found in the NCOR co-repressor complex (Perissi et al. 2004). Once the NCOR complex is displaced, Tbl1x and Tbl1xr1 remain bound to it and facilitate NICD1-mediated transcription probably by acting as adaptors for recruitment of the ubiquitin conjugating/19S proteasome complex that degrades displaced transcriptiona…
right: NICD1:RBPJ:SNW1
right: NCOR:HDAC1:Tbl1

RBPSUH
type: ProteinReference
name: IGKJRB1
name: UniProt:Q06330 RBPJ
name: RBPJ
name: RBPJK
name: IGKJRB
xref: UnificationXref6
comment: FUNCTION Transcriptional regulator that plays a central role in Notch signaling, a signaling pathway involved in cell-cell communication that regulates a broad spectrum of cell-fate determinations. Acts as a transcriptional repressor when it is not associated with Notch proteins. When associated with some NICD product of Notch proteins (Notch intracellular domain), it acts as a transcriptional activator that activates transcription of Notch target genes. Probably represses or activates transcription via the recruitment of chromatin remodeling complexes containing histone deacetylase or histone acetylase proteins, respectively. Specifically binds to the immunoglobulin kappa-type J segment recombination signal sequence. Binds specifically to methylated DNA.SUBUNIT Interacts with activated NOTCH1, NOTCH2 or NOTCH3. Interacts with MINT/SHARP. This interaction may mediate the recruitment of large corepressor complexes containing proteins such as HDAC1, HDAC2, NCOR2, SAP30, FHL1/KYOT2 and CIR1. Interacts with EP300, MAML1 and PTF1A. Interacts with Epstein-Barr virus EBNA2, EBNA3, EBNA4 and EBNA6. Interacts with RITA/C12orf52, leading to nuclear export, prevent the interaction between RBPJ and NICD product and subsequent down-regulation of the Notch signaling pathway. Interacts with SNW1.DISEASE Adams-Oliver syndrome 3 (AOS3) [MIM:614814]: An autosomal dominant form of Adams-Oliver syndrome, a disorder characterized by the congenital absence of skin (aplasia cutis congenita) in combination with transverse limb defects. Aplasia cutis congenita can be located anywhere on the body, but in the vast majority of the cases, it is present on the posterior parietal region where it is often associated with an underlying defect of the parietal bones. Limb abnormalities are typically limb truncation defects affecting the distal phalanges or entire digits (true ectrodactyly). Only rarely, metatarsals/metacarpals or more proximal limb structures are also affected. Apart from transverse …
organism: Homo sapiens

SNW domain-containing protein
type: Protein
entity reference: SKIIP
data source: Reactome
name: SNW1_HUMAN
name: SKIP
xref: UnificationXref30
xref: UnificationXref29
feature: FragmentFeature7
cellular location: nucleoplasm
comment: Reactome DB_ID: 351663
display name: SNW1