Insig1

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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.

Function[edit]

  1. 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 promotor 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 C1 protein, which participates in the intracellular movement of cholesterol
  • Patched, the receptor for Hedgehog, a protein that contains covalently bound cholesterol

Regulation[edit]

INSIG1 is regulated by insulin and highly expressed in liver.

Sequence (277 AA)[edit]

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[edit]

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

References[edit]

External links[edit]