| Post Translational Modifications | Phosphorylation at Ser-151 by PCK1 reduces binding to oxysterol, disrupting the interaction between INSIG2 and SCAP, thereby promoting nuclear translocation of SREBP proteins (SREBF1/SREBP1 or SREBF2/SREBP2) and subsequent transcription of downstream lipogenesis-related genes. Polyubiquitinated by AMFR/gp78 at Cys-215 in some tissues such as adipose tissues, undifferentiated myoblasts and liver, leading to its degradation. In differentiated myotubes, Cys-215 oxidation prevents ubiquitination at the same site, resulting in protein stabilization. Oxidized at Cys-215 in differentiated myotubes, preventing ubiquitination at the same site, and resulting in protein stabilization. |
| Function | Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of SCAP and degradation of HMGCR. Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2. Binds oxysterol, including 22-hydroxycholesterol, 24-hydroxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol, regulating interaction with SCAP and retention of the SCAP-SREBP complex in the endoplasmic reticulum. In presence of oxysterol, interacts with SCAP, retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby preventing SCAP from escorting SREBF1/SREBP1 and SREBF2/SREBP2 to the Golgi. Sterol deprivation or phosphorylation by PCK1 reduce oxysterol-binding, disrupting the interaction between INSIG2 and SCAP, thereby promoting Golgi transport of the SCAP-SREBP complex, followed by processing and nuclear translocation of SREBF1/SREBP1 and SREBF2/SREBP2. Also regulates cholesterol synthesis by regulating degradation of HMGCR: initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligase RNF139. |
| Protein Name | Insulin-Induced Gene 2 ProteinInsig-2 |
| Database Links | Reactome: R-HSA-1655829 |
| Cellular Localisation | Endoplasmic Reticulum MembraneMulti-Pass Membrane Protein |
| Alternative Antibody Names | Anti-Insulin-Induced Gene 2 Protein antibodyAnti-Insig-2 antibodyAnti-INSIG2 antibody |
Information sourced from Uniprot.org
