insulin-induced gene 1 protein; INSIG-1 (INSIG1)

Function

• mediates feedback control of cholesterol synthesis by controlling SCAP & HMGCR
• functions by blocking the processing of sterol regulatory element-binding proteins (SREBPs)
• capable of retaining the SCAP-SREBF2 complex in the endoplasmic reticulum (ER) thus preventing it from escorting SREBPs to the Golgi
• seems to regulate the ubiquitin-mediated proteasomal degradation of HMGCR
• may play a role in growth & differentiation of tissues involved in metabolic control
• may play a regulatory role during G0/G1 transition of cell growth
• ubiquitinated
• subsequent to sterol deprivation, the SCAP-SREBF2 complex becomes dissociated from INSIG1, is then ubiquitinated & 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
• binds to the SCAP-SREBF2 complex only in the presence of sterols
• interacts with RNF139

Structure

belongs to the INSIG family

Compartment

• endoplasmic reticulum membrane; multi-pass membrane protein

Expression

• expressed in all tissues tested
• highest expression in liver
• expression induced by insulin
• expressed at high levels when nuclear SREBP levels are high as a result of sterol deprivation

More general terms

• transmembrane 6 protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=3638
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:3638
• OMIM: https://mirror.omim.org/entry/602055
• UniProt: http://www.uniprot.org/uniprot/O15503.html