ID:INSI1_HUMAN DESCRIPTION: RecName: Full=Insulin-induced gene 1 protein; Short=INSIG-1; FUNCTION: Mediates 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. SUBUNIT: Binds 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. INTERACTION: P00180:CYP2C1 (xeno); NbExp=2; IntAct=EBI-6252425, EBI-6251821; P00181:CYP2C2 (xeno); NbExp=3; IntAct=EBI-6252425, EBI-4320576; SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. TISSUE SPECIFICITY: Expressed in all tissues tested with highest expression in the liver. INDUCTION: By insulin. PTM: Ubiquitinated. 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. MISCELLANEOUS: Expressed at high levels when nuclear SREBP levels are high as a result of sterol deprivation. SIMILARITY: Belongs to the INSIG family. WEB RESOURCE: Name=Wikipedia; Note=Insig1 entry; URL="http://en.wikipedia.org/wiki/Insig1";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O15503
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
