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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)

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 a) the 1st cleavage by site-1 protease occurs within the luminal loop b) 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

General

sterol regulatory element binding protein (SREBP)

Properties

SIZE: entity length = 1147 aa MW = 122 kD COMPARTMENT: cytoplasm cell nucleus golgi endoplasmic reticulum MOTIF: cytoplasmic domain {1-487} MOTIF: Transcriptional activation (acidic) NAME: Transcriptional activation (acidic) SITE: 1-60 serine-rich region {61-178} MOTIF: serine residue (SEVERAL) Tyr phosphorylation site {Y110} LMNA interaction {234-497} MOTIF: DNA-binding motif SITE: 323-336 helix-loop-helix NAME: helix-loop-helix SITE: 337-374 FOR-BINDING-VIA: helix-loop-helix leucine zipper SITE: 373-394 FOR-BINDING-VIA: leucine zipper serine-rich region {427-462} MOTIF: serine residue (SEVERAL) proteolytic site {460-461} transmembrane domain {488-508} MOTIF: proteolytic site {490-491} exoplasmic loop {509-547} MOTIF: proteolytic site {530-531} transmembrane domain {548-568} cytoplasmic domain {569-1147} MOTIF: Ser phosphorylation site {S1019} Ser phosphorylation site {S1020}

Database Correlations

OMIM 184756 UniProt P36956

References

  1. 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: 8402897
  2. Wikipedia; sterol regulatory element- binding protein entry http://en.wikipedia.org/wiki/sterol_regulatory_element_binding_protein
  3. UniProt :accession P36956