DOMAIN Cholesterol bound to SSC domain of SCAP or oxysterol bound to INSIG1/2 leads to masking of an ER export signal on SCAP possibly by moving the signal further away from the ER membrane.SIMILARITY Belongs to the WD repeat SCAP family.SIMILARITY Contains 1 SSD (sterol-sensing) domain.SIMILARITY Contains 7 WD repeats.
INDUCTION By insulin.MISCELLANEOUS Expressed at high levels when nuclear SREBP levels are high as a result of sterol deprivation.SIMILARITY Belongs to the INSIG family.
FUNCTION Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the fatty acid and to a lesser degree the cholesterol synthesis pathway (By similarity). Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3').SUBUNIT Forms a tight complex with SCAP in the ER membrane. Efficient DNA binding of the soluble transcription factor fragment requires dimerization with another bHLH protein. Interacts with LMNA.TISSUE SPECIFICITY Expressed in a wide variety of tissues, most abundant in liver and adrenal gland. In fetal tissues lung and liver shows highest expression. Isoform SREBP-1C predominates in liver, adrenal gland and ovary, whereas isoform SREBP-1A predominates in hepatoma cell lines. Isoform SREBP-1A and isoform SREBP-1C are found in kidney, brain, white fat, and muscle.PTM At low cholesterol the SCAP/SREBP complex is recruited into COPII vesicles for export from the ER. In the Golgi complex SREBPs are cleaved sequentially by site-1 and site-2 protease. The first cleavage by site-1 protease occurs within the luminal loop, the second cleavage by site-2 protease occurs within the first transmembrane domain and releases the transcription factor from the Golgi membrane. Apoptosis triggers cleavage by the cysteine proteases caspase-3 and caspase-7.SIMILARITY Belongs to the SREBP family.SIMILARITY Contains 1 bHLH (basic helix-loop-helix) domain.
Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER
SIMILARITY Belongs to the SEC23/SEC24 family. SEC24 subfamily.
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2033002
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2029554
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1986586
FUNCTION Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity). May play a role during CNS development.TISSUE SPECIFICITY Proliferating neuroepithelium.DEVELOPMENTAL STAGE CNS development.PTM Phosphorylated.PTM Hydroxylated by HIF1AN.SIMILARITY Belongs to the NOTCH family.SIMILARITY Contains 5 ANK repeats.SIMILARITY Contains 34 EGF-like domains.SIMILARITY Contains 3 LNR (Lin/Notch) repeats.
Insig required for sterol-mediated inhibition of Scap/SREBP binding to COPII proteins in vitro
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032355
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_118586.2
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_147932.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655715
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148081.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655767
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119375.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032300
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=205687
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_26764.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2023200
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119496.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2023202
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_120179.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=735682
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_120308.1
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119960.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032271
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_23172.2
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032269
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119015.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032275
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119129.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032274
FUNCTION Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the cholesterol and to a lesser degree the fatty acid synthesis pathway (By similarity). Binds the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') found in the flanking region of the LDRL and HMG-CoA synthase genes.TISSUE SPECIFICITY Ubiquitously expressed in adult and fetal tissues.SIMILARITY Belongs to the SREBP family.SIMILARITY Contains 1 bHLH (basic helix-loop-helix) domain.
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032283
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119494.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032302
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_120031.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032281
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119427.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655733
Identification of complexes between the COOH-terminal domains of sterol regulatory element-binding proteins (SREBPs) and SREBP cleavage-activating protein
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148522.2
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_118874.1
Chaperone activity of protein O-fucosyltransferase 1 promotes notch receptor folding
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032279
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032277
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119944.1
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148184.2
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655735
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148574.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655758
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148176.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655749
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655763
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_147840.1
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148293.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2317526
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_147975.2
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655727
Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655761
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655730
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148171.2
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2326883
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148091.2
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148327.2
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_11015.2
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=193384
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148178.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2317523
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148058.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2317521
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148375.2
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655757
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_147768.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2317528
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655722
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2317524
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148244.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655736
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148247.2
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148265.1
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148138.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2317518
Fringe modifies O-fucose on mouse Notch1 at epidermal growth factor-like repeats within the ligand-binding site and the Abruptex region
Direct binding of cholesterol to the purified membrane region of SCAP: mechanism for a sterol-sensing domain
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=203987
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_12899.2
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655768
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148034.1
TISSUE SPECIFICITY Highly expressed in lung, moderately in heart kidney, and at lower levels in the ovary and skeletal muscle. A very low expression is seen in the brain, intestine, liver and testis.DEVELOPMENTAL STAGE Highly expressed in endothelial cells during embryonic development from 9.0 dpc.PTM Phosphorylated.DISEASE Loss of the extracellular domain causes constitutive activation of the Notch protein, which leads to hyperproliferation of glandular epithelial tissues and development of mammary carcinomas.SIMILARITY Belongs to the NOTCH family.SIMILARITY Contains 5 ANK repeats.SIMILARITY Contains 29 EGF-like domains.SIMILARITY Contains 3 LNR (Lin/Notch) repeats.
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655747
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148424.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655751
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148491.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655750
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_147893.1
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148336.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655840
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_148180.2
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655759
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_22966.3
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=727815
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=727810
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032981
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_120164.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032987
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119065.1
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_22895.2
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032984
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_120048.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032991
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032989
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119099.1
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119275.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032998
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119448.1
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119779.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032999
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2032997
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119098.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2033000
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2033005
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119184.1
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_118591.2
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119856.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1984030
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1984029
MISCELLANEOUS Does not require nuclear SREBPs for its expression. When nuclear SREBP activity is low, is the only form of INSIG present in the cell.SIMILARITY Belongs to the INSIG family.
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119738.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1984032
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_118959.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1984033
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119852.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1984031
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119457.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1463452
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119248.2
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119580.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1986542
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1986553
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119366.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1467290
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119409.1
Cholesterol-induced conformational change in SCAP enhanced by Insig proteins and mimicked by cationic amphiphiles
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1985704
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_120130.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5149526
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_173078.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1986584
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_118648.2
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119295.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1986568
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_119227.1
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1986582
Sterol regulatory element-binding protein 1C
Sterol regulatory element-binding protein 1A
Sterol regulatory element-binding protein 2
Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1655838
Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=REACT_147890.1
PATHWAY Protein modification; protein glycosylation.SIMILARITY Belongs to the glycosyltransferase 68 family.
Modification of epidermal growth factor-like repeats with O-fucose. Molecular cloning and expression of a novel GDP-fucose protein O-fucosyltransferase
In low concentrations of cholesterol SCAP interacts with Sec24 of the CopII coat complex causing SCAP:SREBP1A/1C/2 to be transported with the CopII complex from the endoplasmic reticulum to the Golgi.
Authored: Egan, SE, Orlic-Milacic, M, 2011-11-14
Using Chinese hamster (Cricetulus griseus) ovarian cell lines deficient in different galactosyltransferases, Chen et al. established that beta-4-galactosyltransferase 1 (B4galt1) was necessary for galactosylation of beta 1,3-linked N-acetylglucosaminyl group added by fringe enzymes to O-linked fucosyl residues on Notch1. B4galt1-mediated galactosylation of Notch1 was necessary for fringe-induced modulation of Notch1 signaling. Since the genome of C. griseus has not been completely sequenced, it is possible that annotated C. griseus Notch isoforms do not represent full-length proteins. Annotated C. griseus Notch2 in particular seems truncated. Only those fucosylation and glycosylation sites that are conserved between Chinese hamster, mouse, human and rat are shown. Since the exact preference, if any, of fringe enzymes for Notch O-fucose sites is not known, the extension of an O-fucosyl residue at an unknown position is shown.
SREBP1A/1C/2 is retained in the endoplasmic reticulum by SCAP:cholesterol:INSIG
SREBPs (SREBP1A/1C/2, SREBFs) bind SCAP in the endoplasmic reticulum membrane. Luminal loop 1 of SCAP binds cholesterol (Adams et al. 2003) which prevents SCAP from interacting with Sec24 in the CopII coat complex and allows SCAP to interact with INSIG instead (Sakai et al. 1997, Yang et al. 2002, Dobrosotskaya et al. 2003, Adams et al. 2004, Feramisco et al. 2005, Sun et al. 2005). These interactions retain SCAP:SREBP1A/1C/2 in the endoplasmic reticulum.
SREBP2 (SREBF2) is retained in the endoplasmic reticulum by SCAP:INSIG2:oxysterol
INSIG binds oxysterols and the INSIG:oxysterol complex interacts with SCAP subunits of the SREBP2:SCAP (SREBF2:SCAP) complex (Adams et al. 2004, Radhakrishnan et al. 2007). This interaction retains the SREBP2:SCAP:INSIG:oxysterol complex in the endoplasmic reticulum. From this reaction it is inferred that SREBP1A (SREBF1A) and SREBP1C (SREBF1C) are retained similarly.
SREBP2 (SREBF2 and by inference SREBP1A and SREBP1C) is a transmembrane protein that binds SCAP in the endoplasmic reticulum membrane (Sakai et al. 1997). In the presence of cholesterol or oxysterols SCAP:SREBP2 binds INSIG and is retained in the endoplasmic reticulum (Espenshade et al. 2002, Yabe et al. 2002, Yang et al. 2002, Adams et al. 2003, Dobrosotskaya et al. 2003, Adams et al. 2004, Radhakrishnan et al. 2004, Sun et al. 2005, Sun et al. 2007, Motamed et al. 2011). At cholesterol concentrations below 5 mol% SCAP changes conformation, SCAP:SREBP2 loses interaction with INSIG, binds the CopII coat complex, and is translocated to the Golgi (Adams et al 2004, Feramisco et al. 2005, Radhakrishnan et al. 2008, Motamed et al. 2011).
In the endoplasmic reticulum, Notch receptor precursors are fucosylated on conserved serine and threonine residues in their EGF repeats. The consensus fucosylation site sequence is C2-X(4-5)-S/T-C3, where C2 and C3 are the second and third cysteine residue within the EGF repeat, and X(4-5) is four to five amino acid residues of any type. Only those fucosylation sites that are conserved between human, mouse and rat Notch isoforms are annotated. Fucosylation is performed by the endoplasmic reticulum resident O-fucosyl transferase POFUT1. Fucosylation by POFUT1, initially discovered in Drosophila, is considered to be an essential step in Notch processing and production of a fully functional receptor. Fucosylation of mammalian Notch proteins was studied by exogenously expressing mouse Notch1 in Chinese hamster ovary cell lines.
Using Chinese hamster (Cricetulus griseus) ovary cells that express endogenous Notch1 but do not express endogenous Fringe proteins, Moloney et al. found after introduction of mouse Mfng that mature Notch1 had the Sia-alpha2,3-Gal-beta1,4-GlcNAc-beta1,3-fucitol tetrasaccharide attached to conserved serine and threonine residues in EGF repeats of Notch1 (Moloney et al. 2000). Sialyltransferases that could be involved in formation of this type of tetrasaccharide are St3gal3, St3gal4 and St3gal6 (Harduin-Lepers et al. 2001).
Identification of luminal Loop 1 of Scap protein as the sterol sensor that maintains cholesterol homeostasis
Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins
Fringe is a glycosyltransferase that modifies Notch
Cholesterol and 25-hydroxycholesterol inhibit activation of SREBPs by different mechanisms, both involving SCAP and Insigs
Switch-like control of SREBP-2 transport triggered by small changes in ER cholesterol: a delicate balance
Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: oxysterols block transport by binding to Insig
Proc. Natl. Acad. Sci. U.S.A. 104:6511-8
TISSUE SPECIFICITY High levels in brain and fibroblasts.SIMILARITY Belongs to the SEC23/SEC24 family. SEC23 subfamily.
PTM Ubiquitinated; undergoes 'Lys-29'-linked polyubiquitination catalyzed by ITCH. Monoubiquitination at Lys-1765 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.SIMILARITY Belongs to the NOTCH family.SIMILARITY Contains 5 ANK repeats.SIMILARITY Contains 35 EGF-like domains.SIMILARITY Contains 3 LNR (Lin/Notch) repeats.
TISSUE SPECIFICITY Expressed in the brain, liver, kidney, neuroepithelia, somites, optic vesicles and branchial arches, but not heart.PTM Hydroxylated by HIF1AN.SIMILARITY Belongs to the NOTCH family.SIMILARITY Contains 6 ANK repeats.SIMILARITY Contains 35 EGF-like domains.SIMILARITY Contains 3 LNR (Lin/Notch) repeats.
Fringe modulation of Jagged1-induced Notch signaling requires the action of beta 4galactosyltransferase-1
SIMILARITY Belongs to the small GTPase superfamily. SAR1 family.
Protein O-fucosyltransferase 1 (Pofut1) regulates lymphoid and myeloid homeostasis through modulation of Notch receptor ligand interactions
PTM Phosphorylated.PTM Hydroxylated at Asn-1945 and Asn-2012 by HIF1AN. Hydroxylation reduces affinity for HI1AN and may thus indirectly modulate negative regulation of NICD.SIMILARITY Belongs to the NOTCH family.SIMILARITY Contains 5 ANK repeats.SIMILARITY Contains 36 EGF-like domains.SIMILARITY Contains 3 LNR (Lin/Notch) repeats.
Reconstitution of sterol-regulated endoplasmic reticulum-to-Golgi transport of SREBP-2 in insect cells by co-expression of mammalian SCAP and Insigs
Sterols block binding of COPII proteins to SCAP, thereby controlling SCAP sorting in ER
Roles of Pofut1 and O-fucose in mammalian Notch signaling
Intramembrane aspartic acid in SCAP protein governs cholesterol-induced conformational change
gene ontology term for cellular function