Anti-SREBP-2 Antibody, clone 22D5 clone 22D5, from rabbit

Sterol regulatory element-binding protein 2 (UniProt: Q3U1N2; also known as SREBP-2, Sterol regulatory element-binding transcription factor 2) is encoded by the Srebf2 (also known as Srebp2) gene (Gene ID: 20788) in murine species. SREBPs are a family of transcription factors that regulate lipid homeostasis by controlling the expression of a range of enzymes that are required for endogenous cholesterol, fatty acid, triacylglycerol, and phospholipid synthesis. The three SREBP isoforms known as, SREBP-1a, SREBP-1c, and SREBP-2, have different roles in lipid synthesis. SREBP-1 and SREBP-2 proteins share 47% of homology. SREBP-2 is mainly involved in cholesterol synthesis and SREBP-1c is mainly involved in fatty acid synthesis and insulin induced glucose metabolism and SREBP-1a isoform is involved in both of these pathways. SREBPs are synthetized as inactive precursor proteins that are bound to the endoplasmic reticulum membranes and upon activation, the precursor is cleaved off in a two-step process to release the N-terminal active domain in the nucleus. SREBP precursors are organized into three domains - an N-terminal domain that contains the transactivation domain, a region rich in serine and proline, and the bHLH-LZ region for DNA binding and dimerization. Sterols are shown to inhibit the cleavage of the precursor protein and the mature nuclear form is rapidly catabolized, thereby reducing transcription. It regulates transcription of the LDL receptor gene as well as the cholesterol and to a lesser degree the fatty acid synthesis pathway. It binds the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') found in the flanking region of the LDRL and HMG-CoA synthase genes. The hepatic overexpression of SREBP-2 isoform in mice causes a preferential induction of genes involved in cholesterol biosynthesis. (Ref.: Eberle, D et al. (2004) Biochimie 86(11); 839-48).