Srebf2
Function
Sterol regulatory element-binding protein 2
Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 2), which is embedded in the endoplasmic reticulum membrane. Low sterol concentrations promote processing of this form, releasing the transcription factor form that translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis.
Processed sterol regulatory element-binding protein 2
Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis. Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3'). Regulates transcription of genes related to cholesterol synthesis pathway. Regulates hepatic lipogenesis.
Post-translational modifications
Sterol regulatory element-binding protein 2
Processed in the Golgi apparatus, releasing the protein from the membrane. At low cholesterol the SCAP-SREBP complex is recruited into COPII vesicles for export from the endoplasmic reticulum. In the Golgi, complex SREBPs are cleaved sequentially by site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P) proteases. The first cleavage by site-1 protease occurs within the luminal loop, the second cleavage by site-2 protease occurs within the first transmembrane domain, releasing the transcription factor from the Golgi membrane. Apoptosis triggers cleavage by the cysteine proteases caspase-3 and caspase-7. Cleavage and activation is induced by mediated cholesterol efflux.
Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression.
Processed sterol regulatory element-binding protein 2
Ubiquitinated; the nuclear form has a rapid turnover and is rapidly ubiquitinated and degraded by the proteasome in the nucleus.
Sequence Similarities
Belongs to the SREBP family.
Cellular localization
- Sterol regulatory element-binding protein 2
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- Golgi apparatus membrane
- Multi-pass membrane protein
- Cytoplasmic vesicle
- COPII-coated vesicle membrane
- Multi-pass membrane protein
- At high sterol concentrations, the SCAP-SREBP is retained in the endoplasmic reticulum. Low sterol concentrations promote recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi, where it is processed.
- Processed sterol regulatory element-binding protein 2
- Nucleus
- Transported into the nucleus with the help of importin-beta. Dimerization of the bHLH domain is a prerequisite for importin beta-dependent nuclear import.
Alternative names
Sterol regulatory element-binding protein 2, SREBP-2, Sterol regulatory element-binding transcription factor 2