Insig1
entrez
231070
canonical
uniprot
Q8BGI3
canonical
ensembl
ENSMUSG00000045294
resolver
ensp
ENSMUSP00000061877
resolver
enst
ENSMUST00000059155
resolver
genesymbol
Insig1
resolver
uniprot
A2RSM6
resolver
uniprot
Q3UAX9
resolver
uniprot
Q3UX30
resolver
uniprot_entry
INSI1_MOUSE
resolver
uniprot_sec
A2RSM6
resolver
uniprot_sec
Q3UAX9
resolver
uniprot_sec
Q3UX30
resolver
amino_acid_sequence
MPRLHDHVWNYPSAGAARPYSLPRGMIAAAACPQGPGVPEPEHAPRGQRAGTTGCSARPGSWHHDLVQRSLVLFSFGVVLALVLNLLQIQRNVTLFPDEVIATIFSSAWWVPPCCGTAAAVVGLLYPCIDSHLGEPHKFKREWASVMRCIAVFVGINHASAKLDFANNVQLSLTLAALSLGLWWTFDRSRSGLGLGITIAFLATLITQFLVYNGVYQYTSPDFLYIRSWLPCIFFSGGVTVGNIGRQLAMGVPEKPHSD
uniprot
proteins
function
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:16100574). 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 (Probable). Binds oxysterol, including 25-hydroxycholesterol, regulating interaction with SCAP and retention of the SCAP-SREBP complex in the endoplasmic reticulum (PubMed:16100574). 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:O15503, ECO:0000269|PubMed:16100574, ECO:0000305|PubMed:26311497}.
uniprot
proteins
mass_dalton
28213
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-189 by PCK1 reduces binding to oxysterol, disrupting the interaction between INSIG1 and SCAP, thereby promoting nuclear translocation of SREBP proteins (SREBF1/SREBP1 or SREBF2/SREBP2) and subsequent transcription of downstream lipogenesis-related genes. {ECO:0000250|UniProtKB:O15503}.; PTM: Ubiquitinated by AMFR/gp78 in response to sterol deprivation, leading to its degradation: when the SCAP-SREBP complex becomes dissociated from INSIG1, INSIG1 is then ubiquitinated and degraded in proteasomes. Although ubiquitination is required for rapid INSIG1 degradation, it is not required for release of the SCAP-SREBP complex. Ubiquitinated by RNF139. {ECO:0000250|UniProtKB:O15503}.
uniprot
proteins
protein_family
INSIG family
uniprot
proteins
pubmed
12242332
uniprot
proteins
pubmed
12869692
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16100574
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16955138
uniprot
proteins
pubmed
26311497
uniprot
proteins
pubmed
28849786
uniprot
proteins
sequence_length
259
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:O15503}; Multi-pass membrane protein {ECO:0000250|UniProtKB:O15503}.
uniprot
proteins
transmembrane_region
TRANSMEM 67..89; /note="Helical; Name=1"; /evidence="ECO:0000250|UniProtKB:A1T557"; TRANSMEM 109..126; /note="Helical; Name=2"; /evidence="ECO:0000250|UniProtKB:A1T557"; TRANSMEM 142..164; /note="Helical; Name=3"; /evidence="ECO:0000250|UniProtKB:A1T557"; TRANSMEM 168..186; /note="Helical; Name=4"; /evidence="ECO:0000250|UniProtKB:A1T557"; TRANSMEM 192..213; /note="Helical; Name=5"; /evidence="ECO:0000250|UniProtKB:A1T557"; TRANSMEM 228..245; /note="Helical; Name=6"; /evidence="ECO:0000250|UniProtKB:A1T557
uniprot
proteins