Insig2
entrez
72999
canonical
uniprot
Q91WG1
canonical
ensembl
ENSMUSG00000003721
resolver
ensp
ENSMUSP00000003818
resolver
ensp
ENSMUSP00000065485
resolver
ensp
ENSMUSP00000123747
resolver
ensp
ENSMUSP00000124345
resolver
ensp
ENSMUSP00000140292
resolver
ensp
ENSMUSP00000194650
resolver
enst
ENSMUST00000003818
resolver
enst
ENSMUST00000071064
resolver
enst
ENSMUST00000159085
resolver
enst
ENSMUST00000160968
resolver
enst
ENSMUST00000186915
resolver
genesymbol
Insig2
resolver
uniprot
A0A087WQP7
resolver
uniprot
Q3TMY2
resolver
uniprot
Q8BWP1
resolver
uniprot_entry
A0A087WQP7_MOUSE
resolver
uniprot_entry
INSI2_MOUSE
resolver
uniprot_sec
Q3TMY2
resolver
uniprot_sec
Q8BWP1
resolver
amino_acid_sequence
MAEGETESPRPKKCGPYISSVTSQSVNVVIRGVVLFFIGVFLALVLNLLQIQRNVTLFPPDVITSIFSSAWWVPPCCGTASAVIGLLYPCIDRHLGEPHKFKREWSSVMRCVAVFVGINHASAKVDFDNNFQFSLTLAALSVGLWWTFDRSRSGFGLGVGIAFLATVVTQLLVYNGVYQYTSPDFLYVRSWLPCIFFAGGITMGNIGRQLAMYECKVIAEKSHQE
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:12242332, PubMed:12624180, 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 (PubMed:16100574). 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 (By similarity). 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 INSIG2 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 ligase RNF139 (By similarity). {ECO:0000250|UniProtKB:Q9Y5U4, ECO:0000269|PubMed:12242332, ECO:0000269|PubMed:12624180, ECO:0000269|PubMed:16100574}.
uniprot
proteins
mass_dalton
24915
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-151 by PCK1 reduces binding to oxysterol, disrupting the interaction between INSIG2 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:Q9Y5U4}.; PTM: Polyubiquitinated by AMFR/gp78 at Cys-215 in some tissues such as adipose tissues, undifferentiated myoblasts and liver, leading to its degradation. In differentiated myotubes, Cys-215 oxidation prevents ubiquitination at the same site, resulting in protein stabilization. {ECO:0000250|UniProtKB:Q9Y5U4}.; PTM: Oxidized at Cys-215 in differentiated myotubes, preventing ubiquitination at the same site, and resulting in protein stabilization. {ECO:0000250|UniProtKB:Q9Y5U4}.
uniprot
proteins
protein_family
INSIG family
uniprot
proteins
pubmed
12242332
uniprot
proteins
pubmed
12624180
uniprot
proteins
pubmed
12869692
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16100574
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16955138
uniprot
proteins
pubmed
28849786
uniprot
proteins
sequence_length
225
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9Y5U4}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q9Y5U4}.
uniprot
proteins
transmembrane_region
TRANSMEM 29..51; /note="Helical; Name=1"; /evidence="ECO:0000250|UniProtKB:A1T557"; TRANSMEM 71..88; /note="Helical; Name=2"; /evidence="ECO:0000250|UniProtKB:A1T557"; TRANSMEM 104..126; /note="Helical; Name=3"; /evidence="ECO:0000250|UniProtKB:A1T557"; TRANSMEM 130..148; /note="Helical; Name=4"; /evidence="ECO:0000250|UniProtKB:A1T557"; TRANSMEM 154..175; /note="Helical; Name=5"; /evidence="ECO:0000250|UniProtKB:A1T557"; TRANSMEM 190..207; /note="Helical; Name=6"; /evidence="ECO:0000250|UniProtKB:A1T557
uniprot
proteins