Insulin-induced gene 1 protein

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INSIG1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesINSIG1, CL-6, CL6, insulin induced gene 1
External IDsMGI: 1916289 HomoloGene: 4047 GeneCards: INSIG1
Gene location (Human)
Chromosome 7 (human)
Chr.Chromosome 7 (human)[1]
Chromosome 7 (human)
Genomic location for INSIG1
Genomic location for INSIG1
Band7q36.3Start155,297,776 bp[1]
End155,310,235 bp[1]
RNA expression pattern
PBB GE INSIG1 201627 s at fs.png

PBB GE INSIG1 201625 s at fs.png

PBB GE INSIG1 201626 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_153526

RefSeq (protein)

NP_705746

Location (UCSC)Chr 7: 155.3 – 155.31 MbChr 5: 28.07 – 28.08 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Insulin induced gene 1, also known as INSIG1, is a protein which in humans is encoded by the INSIG1 gene.[5][6]

INSIG1 is short for insulin-induced gene 1; it is located on chromosome 7 (7q36). This human gene encodes for a transmembrane protein of 277 amino acids with probably 6 transmembrane domains. It is localized in the endoplasmic reticulum (ER) 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[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 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-CoA-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:

Oxysterols regulate cholesterol homeostasis through liver X receptor (LXR) and sterol regulatory element-binding protein (SREBP) mediated signaling pathway. 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.[6]

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)

Interactions[edit]

INSIG1 has been shown to interact with SREBF2.[7][8]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000186480 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000045294 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Peng Y, Schwarz EJ, Lazar MA, Genin A, Spinner NB, Taub R (Aug 1997). "Cloning, human chromosomal assignment, and adipose and hepatic expression of the CL-6/INSIG1 gene". Genomics. 43 (3): 278–84. doi:10.1006/geno.1997.4821. PMID 9268630. 
  6. ^ a b "Entrez Gene: INSIG1 insulin induced gene 1". 
  7. ^ Dobrosotskaya IY, Goldstein JL, Brown MS, Rawson RB (Sep 2003). "Reconstitution of sterol-regulated endoplasmic reticulum-to-Golgi transport of SREBP-2 in insect cells by co-expression of mammalian SCAP and Insigs". The Journal of Biological Chemistry. 278 (37): 35837–43. doi:10.1074/jbc.M306476200. PMID 12842885. 
  8. ^ Yang T, Espenshade PJ, Wright ME, Yabe D, Gong Y, Aebersold R, Goldstein JL, Brown MS (Aug 2002). "Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER". Cell. 110 (4): 489–500. doi:10.1016/S0092-8674(02)00872-3. PMID 12202038. 

Further reading[edit]

External links[edit]