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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
Related
sterol regulatory element binding protein-2 (SREBP-2) gene
General
sterol regulatory element binding protein (SREBP)
transmembrane 2 protein
Properties
SIZE: MW = 124 kD
entity length = 1141 aa
COMPARTMENT: cytoplasm
cell nucleus
golgi
endoplasmic reticulum
MOTIF: cytoplasmic domain {1-479}
MOTIF: transcriptional activation domain
SITE: 1-50
serine-rich region {52-124}
MOTIF: serine residue (SEVERAL)
glutamine-rich region {125-244}
MOTIF: glutamine residue (SEVERAL)
DNA-binding motif
SITE: 330-343
helix-loop-helix
NAME: helix-loop-helix
SITE: 344-381
FOR-BINDING-VIA: helix-loop-helix
leucine zipper
SITE: 380-401
FOR-BINDING-VIA: leucine zipper
proteolytic site {468-469}
transmembrane domain {480-500}
MOTIF: proteolytic site {490-491}
exoplasmic loop {501-533}
MOTIF: proteolytic site {522-523}
transmembrane domain {534-554}
cytoplasmic domain {555-1139}
MOTIF: alanine residue {591-595} (5)
Database Correlations
OMIM 600481
UniProt Q12772
Pfam PF00010
Kegg hsa:6721
References
- Hua et al,
SREBP-2, a second basic helix-loop-helix-leucine zipper protein
that stimulates transcription by binding to a sterol regulatory
element.
Proc Nat Acad Sci USA 90:11603 1993
PMID: 7903453
- UniProt :accession Q12772