Suvarna Garge (Editor)

Insulin induced gene 1 protein

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Species
  
Human

Entrez
  
3638

Human
  
Mouse

Ensembl
  
ENSG00000186480

Insulin-induced gene 1 protein

Aliases
  
INSIG1, CL-6, CL6, insulin induced gene 1

External IDs
  
MGI: 1916289 HomoloGene: 4047 GeneCards: INSIG1

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

Contents

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

  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 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
  • 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.

    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 SREBF2.

    References

    Insulin-induced gene 1 protein Wikipedia
    (Text) CC BY-SA