INSIG1 (Vector pUC, Accession No. BC001880)

Length: 834 Sequence: atgcccagat tgcacgacca cttctggagc tgctcctgtg cgcacagcgc gaggcgccga ggccccccgc gagccagcgc cgcggggctg gcggccaagg ttggggagat gatcaacgtt tccgtgtccg ggccctccct gctggcggcc cacggtgccc cggacgctga ccccgcgccc aggggccgca gtgctgcgat gagcggcccc gagcccggca gcccctaccc caacacctgg catcatcgcc tgttgcagag gagcctcgtg ctcttctcgg ttggggtggt cctagccctg gtgctcaacc tgctgcagat ccagaggaat gtcactctct tccccgagga ggtgatcgcc accatctttt cctccgcctg gtgggtccct ccctgctgcg ggacagcagc tgctgttgtt ggcctactgt acccctgtat cgacagtcac ctcggagaac cccacaaatt taagagagaa tgggccagtg tcatgcgctg catagcagtt tttgttggca ttaaccacgc cagtgctaaa ttggattttg ccaataatgt ccagctgtcc ttgactttag cagccctatc tttgggcctt tggtggacat ttgatcgttc cagaagtggc cttgggctgg ggatcaccat agcttttcta gctacgctga tcacgcagtt tctcgtgtat aatggtgtct atcagtatac atccccagat ttcctctata ttcgttcttg gctcccttgt atatttttct caggaggcgt cacggtgggg aacataggac gacagttagc tatgggtgtt cctgaaaagc cccatagtga Protein 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:12202038, PubMed:12535518, PubMed:16168377, PubMed:16399501, 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:12202038, PubMed:16399501, PubMed:32322062). Binds oxysterol, including 25-hydroxycholesterol, regulating interaction with SCAP and retention of the SCAP-SREBP complex in the endoplasmic reticulum (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:15899885, PubMed:32322062). Sterol deprivation or phosphorylation by PCK1 reduce oxysterol-binding, disrupting the interaction between INSIG1 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 ligases AMFR/gp78 and/or RNF139 (PubMed:12535518, PubMed:16168377, PubMed:22143767). Also regulates degradation of SOAT2/ACAT2 when the lipid levels are low: initiates the ubiquitin-mediated degradation of SOAT2/ACAT2 via recruitment of the ubiquitin ligases AMFR/gp78 (PubMed:28604676). [The UniProt Consortium]