InterPro domain: IPR025929

This family contains a number of eukaryotic Insulin-induced proteins (INSIG-1 and INSIG-2) approximately 200 residues long. INSIG-1 and INSIG-2 are found in the endoplasmic reticulum and bind the sterol-sensing domain of SREBP cleavage-activating protein (SCAP), preventing it from escorting SREBPs to the Golgi. Their combined action permits feedback regulation of cholesterol synthesis over a wide range of sterol concentrations [ 1 , 2 ].

The INSIG family also includes NSG1 and NSG2 (INSIG homologues 1 and 2) [ 3 ].

1. Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell 110, 489-500
2. Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins. Proc. Natl. Acad. Sci. U.S.A. 99, 12753-8
3. INSIG: a broadly conserved transmembrane chaperone for sterol-sensing domain proteins. EMBO J. 24, 3917-26