LMPD Database

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LMP012693

UniProt Annotations

Entry Information
Gene Nameinsulin induced gene 1
Protein EntryINSI1_RAT
UniProt IDQ08755
SpeciesRat
Comments
Comment typeDescription
FunctionMediates feedback control of cholesterol synthesis by controlling SCAP and HMGCR. Functions by blocking the processing of sterol regulatory element-binding proteins (SREBPs). Capable of retaining the SCAP-SREBF2 complex in the ER thus preventing it from escorting SREBPs to the Golgi. Initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligase, AMFR/gp78. May play a role in growth and differentiation of tissues involved in metabolic control. May play a regulatory role during G0/G1 transition of cell growth (By similarity)
InductionBy insulin and hepatectomy.
PtmUbiquitinated. Subsequent to sterol deprivation, the SCAP- SREBF2 complex becomes dissociated from 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 (By similarity)
SimilarityBelongs to the INSIG family
Subcellular LocationEndoplasmic reticulum membrane {ECO:0000250}; Multi-pass membrane protein .
SubunitBinds to the SCAP-SREBF2 complex only in the presence of sterols. Interacts with RNF139. Interacts with HMGCR (via its SSD); the interaction, accelerated by sterols, leads to the recruitment of HMGCR to AMFR/gp78 for its ubiquitination by the sterol-mediated ERAD pathway. Interacts with AMFR/gp78 (via its membrane domain); the interaction recruits HMCR at the ER membrane for its ubiquitination and degradation by the sterol-mediated ERAD pathway (By similarity)
Tissue SpecificityHighly expressed in liver and kidney.