LMPD Database

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LMP000786

UniProt Annotations

Entry Information
Gene Namesterol regulatory element binding transcription factor 1
Protein EntrySRBP1_MOUSE
UniProt IDQ9WTN3
SpeciesMouse
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Comment=Additional isoforms seem to exist.; Name=SREBP-1A; IsoId=Q9WTN3-1; Sequence=Displayed; Name=SREBP-1A-W42; IsoId=Q9WTN3-2; Sequence=VSP_002152; Name=SREBP-1C; IsoId=Q9WTN3-3; Sequence=VSP_002151; Name=SREBP-1C-W42; IsoId=Q9WTN3-4; Sequence=VSP_002151, VSP_002152;
Disruption PhenotypeMice show high embryonic lethality around day 11 dpc. Surviving mice show a 2-3-fold increase in processed Srebpf2 protein in liver nuclei, 3-fold increase in cholesterol synthesis and 50% increase in cholesterol content of the liver. Mice lacking isoform SREBP-1C show a lack of up-regulation of several lipogenic enzymes in response to high insulin or LXR activation. Mice overexpressing processed isoform SREBP-1A in adipocytes show enlarged white and brown adipocytes, increased rate of fatty acid synthesis and secretion leading to a fatty liver. Mice overexpressing processed isoform SREBP-1C in adipocytes show inhibition of adipocyte differentiation leading to a syndrome similar to human lipodystrophy with loss of peripheral white adipose tissue, diabetes and fatty liver. {ECO:0000269|PubMed:11782483, ECO:0000269|PubMed:9329978}.
FunctionTranscriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the fatty acid and to a lesser degree the cholesterol synthesis pathway. 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'). Isoform SREBP-1A is much more active than isoform SREBP-1C in stimulating transcription from SRE-1-containing promoters. {ECO:0000269|PubMed:11782483, ECO:0000269|PubMed:12855691, ECO:0000269|PubMed:9329978, ECO:0000269|PubMed:9784493}.
InductionIsoform SREBP-1C is expressed in a circadian manner in the liver with a peak at ZT16. {ECO:0000269|PubMed:19786558}.
InteractionQ923E4:Sirt1; NbExp=2; IntAct=EBI-5273743, EBI-1802585;
PtmAt 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 and site-2 protease. 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 and releases the transcription factor from the Golgi membrane. Apoptosis triggers cleavage by the cysteine proteases caspase-3 and caspase-7.
PtmPhosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression. Phosphorylation at Ser-389 by SIK1 represses activity possibly by inhibiting DNA-binding. {ECO:0000269|PubMed:19244231, ECO:0000269|PubMed:21459323}.
SimilarityBelongs to the SREBP family. {ECO:0000305}.
SimilarityContains 1 bHLH (basic helix-loop-helix) domain. {ECO:0000255|PROSITE-ProRule:PRU00981}.
Subcellular LocationEndoplasmic reticulum membrane {ECO:0000269|PubMed:21459323}; Multi-pass membrane protein {ECO:0000269|PubMed:21459323}. Golgi apparatus membrane {ECO:0000269|PubMed:21459323}; Multi-pass membrane protein {ECO:0000269|PubMed:21459323}. Cytoplasmic vesicle, COPII-coated vesicle membrane {ECO:0000269|PubMed:21459323}; Multi-pass membrane protein {ECO:0000269|PubMed:21459323}. Note=Moves from the endoplasmic reticulum to the Golgi in the absence of sterols.
Subcellular LocationProcessed sterol regulatory element-binding protein 1: Nucleus.
SubunitForms 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. {ECO:0000269|PubMed:11929849}.
Tissue SpecificityIsoform SREBP-1C predominates in liver, adrenal gland, brain and adipose tissue, whereas isoform SREBP-1A predominates in spleen. Isoform SREBP-1A and isoform SREBP-1C are found in kidney, thymus, testis, muscle, jejunum, and ileum.