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MGP001640

UniProt Annotations

Entry Information
Gene Nameinsulin induced gene 1
Protein EntryINSI1_HUMAN
UniProt IDO15503
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=O15503-1; Sequence=Displayed; Name=2; IsoId=O15503-2; Sequence=VSP_045084, VSP_045085; Note=No experimental confirmation available.;
FunctionMediates feedback control of cholesterol synthesis by controlling SCAP and HMGCR. Functions by blocking the processing of sterol regulatory element-binding proteins (SREBPs). Capable of retaining the SCAP-SREBF2 complex in the ER thus preventing it from escorting SREBPs to the Golgi. Initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligase, AMFR/gp78. May play a role in growth and differentiation of tissues involved in metabolic control. May play a regulatory role during G0/G1 transition of cell growth. {ECO:0000269|PubMed:12202038, ECO:0000269|PubMed:12535518, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:16399501, ECO:0000269|PubMed:16606821}.
InductionBy insulin.
InteractionP00180:CYP2C1 (xeno); NbExp=2; IntAct=EBI-6252425, EBI-6251821; P00181:CYP2C2 (xeno); NbExp=3; IntAct=EBI-6252425, EBI-4320576;
MiscellaneousExpressed at high levels when nuclear SREBP levels are high as a result of sterol deprivation.
PtmUbiquitinated. Subsequent to sterol deprivation, the SCAP- SREBF2 complex becomes dissociated from INSIG1, is then ubiquitinated and degraded in proteasomes. Although ubiquitination is required for rapid INSIG1 degradation, it is not required for release of the SCAP-SREBP complex. Ubiquitinated by RNF139. {ECO:0000269|PubMed:16399501, ECO:0000269|PubMed:20068067}.
SimilarityBelongs to the INSIG family. {ECO:0000305}.
Subcellular LocationEndoplasmic reticulum membrane {ECO:0000269|PubMed:12202038}; Multi-pass membrane protein {ECO:0000269|PubMed:12202038}.
SubunitBinds to the SCAP-SREBF2 complex only in the presence of sterols. Interacts with RNF139. Interacts with HMGCR (via its SSD); the interaction, accelerated by sterols, leads to the recruitment of HMGCR to AMFR/gp78 for its ubiquitination by the sterol-mediated ERAD pathway. Interacts with AMFR/gp78 (via its membrane domain); the interaction recruits HMCR at the ER membrane for its ubiquitination and degradation by the sterol-mediated ERAD pathway. {ECO:0000269|PubMed:12202038, ECO:0000269|PubMed:12535518, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:16399501, ECO:0000269|PubMed:20068067}.
Tissue SpecificityExpressed in all tissues tested with highest expression in the liver. {ECO:0000269|PubMed:12202038}.
Web ResourceName=Wikipedia; Note=Insig1 entry; URL="http://en.wikipedia.org/wiki/Insig1";
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