Insulin-induced gene 1 protein
Insulin induced gene 1, also known as INSIG1, is a protein which in humans is encoded by the INSIG1 gene.
INSIG1 is short for insulin-induced gene 1; it is located on chromosome 7. This human gene encodes for a transmembrane protein of 277 amino acids with probably 6 transmembrane domains. It is localized in the endoplasmic reticulum and seems to be expressed in all tissues, especially in liver. This gene is called an insulin-induced gene because the molecule insulin can regulate it. Importantly, the protein encoded by this gene plays a critical role in regulating cholesterol concentrations in cells.
Function
- INSIG1 plays an important role in the Sterol [regulatory element binding protein|SREBP]-mediated regulation of cholesterol biosynthesis: by binding to the sterol-sensing domain of SCAP it makes the SCAP/SREBP complex stay longer in the ER, thus prohibiting SCAP from carrying activated SREBP to the golgi complex. This ultimately blocks SREBP from acting as a transcription factor for the SRE in the promoter region of the HMG-CoA-reductase gene and results in a decreased expression of HMG-CoA-reductase.
- INSIG1 also binds to the sterol-sensing domain of HMG-CoA-reductase, resulting in the enzyme's increased degradation.
There are two other proteins whose sterol-binding sites show a great similarity to the ones of SCAP and HMG-CoA-reductase and who might thus be regulated by INSIG1 as well:
- Niemann-Pick disease type C1 protein, which participates in the intracellular movement of cholesterol
- Patched, the receptor for Hedgehog, a protein that contains covalently bound cholesterol