Insulin-induced gene 1 protein (INSIG-1)
1_MPRLH 6_ DHFWS 11_ CSCAH 16_ SARRR 21_ GPPRA 26_ SAAGL 31_ AAKVG 36_ EMINV 41_ SVSGP 46_ SLLAA 51_ HGAPD 56_ ADPAP 61_ RGRSA 66_ AMSGP 71_ EPGSP 76_ YPNTW 81_ HHRLL 86_ QRSLV 91_ LFSVG 96_ VVLAL 101_ VLNLL 106_ QIQRN 111_ VTLFP 116_ EEVIA 121_ TIFSS 126_ AWWVP 131_ PCCGT 136_ AAAVV 141_ GLLYP 146_ CIDSH 151_ LGEPH 156_ KFKRE 161_ WASVM 166_ RCIAV 171_ FVGIN 176_ HASAK 181_ LDFAN 186_ NVQLS 191_ LTLAA 196_ LSLGL 201_ WWTFD 206_ RSRSG 211_ LGLGI 216_ TIAFL 221_ ATLIT 226_ QFLVY 231_ NGVYQ 236_ YTSPD 241_ FLYIR 246_ SWLPC 251_ IFFSG 256_ GVTVG 261_ NIGRQ 266_ LAMGV 271_PEKPH
1: 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:26311497, 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:26311497, 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)