Insulin-induced gene 1 protein

Insulin induced gene 1, also known as INSIG1, is a is_associated_with::protein which in humans is encoded by the INSIG1 is_associated_with::gene.

INSIG1 is short for is_associated_with::insulin-induced is_associated_with::gene 1; it is located on is_associated_with::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 is_associated_with::liver.

Function

 * 1) INSIG1 plays an important role in the SREBP-mediated regulation of is_associated_with::cholesterol biosynthesis: by binding to the is_associated_with::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 is_associated_with::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.
 * 2) 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:
 * Niemann-Pick disease type C1 protein, which participates in the intracellular movement of cholesterol
 * is_associated_with::Patched, the receptor for Hedgehog, a protein that contains covalently bound cholesterol

is_associated_with::Oxysterols regulate cholesterol homeostasis through liver X receptor (LXR) and sterol regulatory element-binding protein (SREBP) mediated signaling pathway. This gene is an is_associated_with::insulin-induced gene. It encodes an is_associated_with::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 is_associated_with::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.

Regulation
INSIG1 is regulated by insulin and highly expressed in liver.

Sequence (277 AA)
MPRLHDHFWS CSCAHSARRR GPPRASTAGL PPKVGEMINV SVSGPSLLAA HGAPDADPAP RGRSAAMSGP EPGSPYPNTW HHRLLQRSLV LFSVGVVLAL VLNLLQIQRN VTLFPEEVIA TIFSSAWWVP PCCGTAAAVV GLLYPCIDSH LGEPHKFKRE WASVMRCIAV FVGINHASAK LDFANNVQLS LTLAALSLGL WWTFDRSRSG LGLGITIAFL ATLITQFLVY NGVYQYTSPD FLYIRSWLPC IFFSGGVTVG NIGRQLAMGV PEKPHSD

Synonyms
CL-6, INSIG-1, Insulin-induced gene 1 protein, MGC1405 (source: iHOP)

Interactions
INSIG1 has been shown to interact with is_associated_with::SREBF2.