Summary

Name INSIG2
Full Name Insulin-induced gene 2 protein
Synonyms INSIG-2 |
Primary ID Q9Y5U4
Links - -
Type protein
Relations 5
Pathways FAP: INSR
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

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Relations

Regulator Mechanism target score
+ up-regulates quantity by expression img/direct-activation.png transcriptional regulation INSIG2 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png ubiquitination INSIG2 0.451
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/indirect_inhibition.png INSIG2 0.2
Publications: 1 Organism: Mus Musculus
Tissue: Liver
+ down-regulates quantity by repression img/indirect_inhibition.png INSIG2 0.2
Publications: 1 Organism: Mus Musculus
+ down-regulates activity img/direct_inhibition.png binding SCAP 0.705
Publications: 1 Organism: Cricetulus Griseus