sterol regulatory element-binding protein 1; SREBP-1; sterol regulatory element-binding transcription factor 1 [contains: processed sterol regulatory element-binding protein 1] (SREBF1, SREBP1)
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Function
- transcriptional activator required for lipid homeostasis
- activates transcription from genes with promoters containing the sterol regulatory element-1 in sterol depleted cells
- silenced by sterols
- regulates transcription of the LDL receptor gene as well as the fatty acid & to a lesser degree the cholesterol synthesis pathway (putative)
- 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') & to SRE-1 (5'-ATCACCCCAC-3')
- 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
- the 1st cleavage by site-1 protease occurs within the luminal loop
- the 2nd cleavage by site-2 protease occurs within the 1st transmembrane domain & releases SREBP1 from the Golgi membrane
- apoptosis triggers cleavage by the cysteine proteases caspase-3 & caspase-7
Structure
- belongs to the SREBP family
- 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-binding protein 1: nucleus
Alternative splicing
named isoforms=4
Expression
- expressed in a wide variety of tissues
- most abundant in liver & adrenal gland
- in fetal tissues, lung & liver shows highest expression
- isoform SREBP-1C predominates in liver, adrenal gland & ovary
- isoform SREBP-1A predominates in hepatoma cell lines
- isoform SREBP-1A & isoform SREBP-1C are found in kidney, brain, white fat, & muscle
More general terms
References
- ↑ Yokoyama et al, SREBP-1, a basic helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. Cell 75:187 1993 PMID: https://www.ncbi.nlm.nih.gov/pubmed/8402897
- ↑ Wikipedia; sterol regulatory element- binding protein entry http://en.wikipedia.org/wiki/sterol_regulatory_element_binding_protein
- ↑ UniProt http://www.uniprot.org/uniprot/P36956.html