Insulin induced gene 1, also known as INSIG1, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

which in humans is encoded by the ''INSIG1''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. INSIG1 is short for insulin-induced

1; it is located on

chromosome 7 Chromosome 7 is one of the 23 pairs of chromosomes in humans, who normally have two copies of this chromosome. Chromosome 7 spans about 159 million base pairs (the building material of DNA) and represents between 5 and 5.5 percent of the total D ...

(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 The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

. 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

#INSIG1 plays an important role in the

SREBP Sterol regulatory element-binding proteins (SREBPs) are transcription factors that bind to the sterol regulatory element DNA sequence TCACNCCAC. Mammalian SREBPs are encoded by the genes '' SREBF1'' and ''SREBF2''. SREBPs belong to the basic- ...

-mediated regulation of

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

biosynthesis: by binding to the sterol-sensing domain of

SCAP SCAP may refer to: * S.C.A.P., an early French manufacturer of cars and engines * Security Content Automation Protocol * ''The Shackled City Adventure Path'', a role-playing game * SREBP cleavage activating protein * Supervisory Capital Assessment ...

(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-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: * Niemann-Pick disease type C1 protein, which participates in the intracellular movement of cholesterol *

Patched Patched (Ptc) is a conserved 12-pass transmembrane protein receptor that plays an obligate negative regulatory role in the Hedgehog signaling pathway in insects and vertebrates. Patched is an essential gene in embryogenesis for proper segme ...

, the receptor for Hedgehog, a protein that contains covalently bound cholesterol

Oxysterol An oxysterol is a derivative of cholesterol obtained by oxidation involving enzymes and / or pro-oxidants. Such compounds play important roles in various biological processes such as cholesterol homeostasis, lipid metabolism (sphingolipids, fatty ...

s regulate cholesterol homeostasis through liver X receptor ( LXR) and sterol regulatory element-binding protein (

) mediated signaling pathway. This protein binds to the sterol-sensing domains of SREBP cleavage-activating protein (

) 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 Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with

SREBF2 Sterol regulatory element-binding protein 2 (SREBP-2) also known as sterol regulatory element binding transcription factor 2 (SREBF2) is a protein that in humans is encoded by the ''SREBF2'' gene. Function This gene encodes a ubiquitously expr ...

References

External links

Uniprot description of INSIG1