Srebf1
Domain
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
Function
Sterol regulatory element-binding protein 1
Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane (PubMed:11782483, PubMed:12855691, PubMed:19244231). 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 and lipid homeostasis (PubMed:11782483, PubMed:12855691, PubMed:16100574, PubMed:19244231).
Processed sterol regulatory element-binding protein 1
Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis (PubMed:17290224, PubMed:19244231, PubMed:21459323, PubMed:9329978, PubMed:9784493). Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') (By similarity). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3') (By similarity). Regulates the promoters of genes involved in cholesterol biosynthesis and the LDL receptor (LDLR) pathway of sterol regulation (PubMed:17290224, PubMed:19244231, PubMed:21459323, PubMed:9329978, PubMed:9784493).
Isoform SREBP-1A
Isoform expressed only in select tissues, which has higher transcriptional activity compared to SREBP-1C (PubMed:12855691, PubMed:21531336). Able to stimulate both lipogenic and cholesterogenic gene expression (PubMed:8833906). Has a role in the nutritional regulation of fatty acids and triglycerides in lipogenic organs such as the liver (PubMed:12855691, PubMed:9062341). Required for innate immune response in macrophages by regulating lipid metabolism (PubMed:21531336).
Isoform SREBP-1C
Predominant isoform expressed in most tissues, which has weaker transcriptional activity compared to isoform SREBP-1A (PubMed:12855691, PubMed:21531336). Primarily controls expression of lipogenic gene (PubMed:8833906, PubMed:9062341). Strongly activates global lipid synthesis in rapidly growing cells (PubMed:8833906, PubMed:9062341).
Post-translational modifications
Sterol regulatory element-binding protein 1
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 (By similarity). 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 (By similarity).
Phosphorylated 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.
Processed sterol regulatory element-binding protein 1
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.
Tissue Specificity
Isoform SREBP-1C
Predominant isoform expressed in most tissues (PubMed:21531336). Predominates in liver, adrenal gland, brain and adipose tissue (PubMed:9062340). Also found in kidney, thymus, testis, muscle, jejunum, and ileum (PubMed:9062340).
Isoform SREBP-1A
Expressed only in select tissues, such as intestinal epithelial, heart, macrophage and bone marrow dendritic cells (PubMed:21531336, PubMed:9062340). Also found in kidney, thymus, testis, muscle, jejunum, and ileum (PubMed:9062340).
Cellular localization
- Sterol regulatory element-binding protein 1
- 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 (PubMed:21459323). Low sterol concentrations promote recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi, where it is processed (PubMed:21459323).
- Processed sterol regulatory element-binding protein 1
- Nucleus
Alternative names
Srebp1, Srebf1, Sterol regulatory element-binding protein 1, SREBP-1, Sterol regulatory element-binding transcription factor 1