Insulin induced gene 1, also known as INSIG1, is a protein which in humans is encoded by the INSIG1gene.
INSIG1 is short for insulin-induced gene 1; it is located on chromosome 7 (7q36). This human gene encodes for a 277 AA long transmembrane protein with probably 6 transmembrane domains. It is localized in the ER and seems to be expressed in all tissues, especially in liver.
INSIG1 plays an important role in the SREBP-mediated regulation of cholesterol biosynthesis: by binding to the sterol-sensing domain of SCAP (SREBP cleavage activating protein) 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-Co-A-reductase, resulting in the enzyme's increased degradation.
Both functions require the binding of INSIG1 protein via the same site.
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:
Patched, the receptor for Hedgehog, a protein that contains covalently bound cholesterol
Oxysterols regulate cholesterol homeostasis through liver X receptor (LXR) and sterol regulatory element-binding protein (SREBP) mediated signaling pathway. This gene is an insulin-induced gene. It encodes an endoplasmic reticulum (ER) membrane protein that plays a critical role in regulating cholesterol concentrations in cells. This protein binds to the sterol-sensing domains of SREBP cleavage-activating protein (SCAP) and HMG CoA reductase, and is essential for the sterol-mediated trafficking of the two proteins. Alternatively spliced transcript variants encoding distinct isoforms have been observed.
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