sterol regulatory element binding protein-2 (SREBP2)

Function

• transcriptional activator
• required for lipid homeostasis
• regulates transcription of the LDL receptor gene, cholesterol biosynthesis & to a lesser degree fatty acid biosynthesis (putative)
• activates transcription from genes with promoters containing the sterol regulatory element-1 in sterol depleted cells
• silenced by sterols
• binds the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') found in the flanking region of the LDRL & HMG-CoA synthase genes
• forms a tight complex with SCAP in the ER membrane
• efficient DNA binding of the soluble transcription factor fragment requires dimerization with another bHLH protein
• interacts with LMNA
• at low cholesterol the SCAP/SREBP complex is recruited into COPII vesicles for export from the ER
• in the Golgi complex SREBPs are cleaved sequentially by site-1 & site-2 protease
• 1st cleavage by site-1 protease occurs within the luminal loop; 2nd cleavage by site-2 protease occurs within the 1st transmembrane domain & releases the transcription factor from the Golgi membrane
• apoptosis triggers cleavage by the cysteine proteases caspase-3 & caspase-7

Structure

• belongs to the SREBP family
• SREBP1 & SREBP2 are 47% identical
• contains 1 basic helix-loop-helix (bHLH) domain

Compartment

• endoplasmic reticulum membrane
• Golgi membrane
• cytoplasmic vesicle, COPII-coated vesicle membrane
• moves from the endoplasmic reticulum to the Golgi in the absence of sterols
• processed sterol regulatory element-bindingprotein 2: nucleus

Expression

• ubiquitously expressed in adult & fetal tissues

More general terms

• sterol regulatory element binding protein (SREBP)
• transmembrane 2 protein

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:6721
• OMIM: https://mirror.omim.org/entry/600481
• UniProt: http://www.uniprot.org/uniprot/Q12772.html