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Identification
HMDB Protein ID HMDBP12298
Secondary Accession Numbers None
Name Insulin-induced gene 2 protein
Synonyms
  1. INSIG-2
Gene Name INSIG2
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of SCAP and degradation of HMGCR (PubMed:12242332, PubMed:16606821, PubMed:32322062). Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:32322062). Binds oxysterol, including 22-hydroxycholesterol, 24-hydroxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol, regulating interaction with SCAP and retention of the SCAP-SREBP complex in the endoplasmic reticulum (PubMed:26160948, PubMed:17428920, PubMed:32322062). In presence of oxysterol, interacts with SCAP, retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby preventing SCAP from escorting SREBF1/SREBP1 and SREBF2/SREBP2 to the Golgi (PubMed:32322062). Sterol deprivation or phosphorylation by PCK1 reduce oxysterol-binding, disrupting the interaction between INSIG2 and SCAP, thereby promoting Golgi transport of the SCAP-SREBP complex, followed by processing and nuclear translocation of SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:32322062). Also regulates cholesterol synthesis by regulating degradation of HMGCR: initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligase RNF139 (PubMed:16606821, PubMed:22143767).
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
SREBP signaling pathway
SREBP-SCAP complex retention in endoplasmic reticulum
cholesterol biosynthetic process
sterol biosynthetic process
cellular response to insulin stimulus
Cellular Component
endoplasmic reticulum membrane
endoplasmic reticulum
SREBP-SCAP-Insig complex
Molecular Function
oxysterol binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 225
Molecular Weight 24777.72
Theoretical pI 7.952
Pfam Domain Function
Signals Not Available
Transmembrane Regions
  • 29-51;71-88;104-126;130-148;154-175;190-207;
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q9Y5U4
UniProtKB/Swiss-Prot Entry Name INSI2_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  14. Zhou ZS, Li MX, Liu J, Jiao H, Xia JM, Shi XJ, Zhao H, Chu L, Liu J, Qi W, Luo J, Song BL: Competitive oxidation and ubiquitylation on the evolutionarily conserved cysteine confer tissue-specific stabilization of Insig-2. Nat Commun. 2020 Jan 17;11(1):379. doi: 10.1038/s41467-019-14231-w. [PubMed:31953408 ]
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