Insig2
entrez
288985
canonical
uniprot
Q80UA9
canonical
ensembl
ENSRNOG00000002478
resolver
ensp
ENSRNOP00000003391
resolver
enst
ENSRNOT00000003391
resolver
genesymbol
Insig2
resolver
uniprot
A0A8L2Q1M5
resolver
uniprot_entry
A0A8L2Q1M5_RAT
resolver
uniprot_entry
INSI2_RAT
resolver
amino_acid_sequence
MAEGETESPRPKKRGPYISSVTSQSVNVVIRGVVLFFIGVFLALVLNLLQIQRNVTLFPPDVITSIFSSAWWVPPCCGTASAVIGLLYPCIDRHLGEPHKFKREWSSVMRCVAVFVGINHASAKVDFDNNFQFSLTLAALSVGLWWTFDRSRSGFGLGVGIAFLATVVTQLLVYNGVYQYTSPDFLYVRSWLPCIFFAGGITMGNIGRQLAMYECKVIAEKSHQE
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. 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. 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. 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. 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. 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. {ECO:0000250|UniProtKB:Q9Y5U4}.
uniprot
proteins
mass_dalton
24968
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
12624180
uniprot
proteins
pubmed
15489334
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