SREBF1
GeneName
SREBF1
Summary
SREBF1, also known as SREBP-1 or ADD1, is a 122 kDa transcription factor that plays a pivotal role in the regulation of lipid metabolism and cellular responses to nutritional signals. It is primarily localised in the nucleus and the endoplasmic reticulum, where it binds to chromatin and regulates the expression of genes involved in cholesterol and fatty acid biosynthesis. SREBF1 functions as a DNA-binding transcription activator, specifically influencing RNA polymerase II-mediated transcription. It is involved in various biological processes, including fat cell differentiation, insulin receptor signalling, and the response to starvation and fatty acids.
Importance
SREBF1 is relevant to: - Lipid metabolism and obesity, as it regulates genes involved in cholesterol and triglyceride synthesis - Diabetes and metabolic syndrome through its role in insulin secretion and sensitivity - Cardiovascular diseases due to its influence on lipid profiles and atherosclerosis - Cancer biology, since altered lipid metabolism can affect tumour growth and survival
Top Products
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Abcam Product Citation Summary
The data indicates that SREBF1 is being studied in various contexts, particularly in relation to its role in human diseases and cellular processes. The use of antibodies in both Western blotting and immunohistochemistry highlights the importance of SREBF1 in understanding mechanisms such as cardiac hypertrophy, ER stress response, and its relationship with other proteins like MMP7.
Abcam Product Citation Table
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:32322062). 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 (By similarity).
Processed sterol regulatory element-binding protein 1
Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis (PubMed:12177166, PubMed:32322062, PubMed:8402897). 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') (PubMed:12177166, PubMed:8402897). Regulates the promoters of genes involved in cholesterol biosynthesis and the LDL receptor (LDLR) pathway of sterol regulation (PubMed:12177166, PubMed:32322062, PubMed:8402897).
Isoform SREBP-1A
Isoform expressed only in select tissues, which has higher transcriptional activity compared to SREBP-1C (By similarity). Able to stimulate both lipogenic and cholesterogenic gene expression (PubMed:12177166, PubMed:32497488). Has a role in the nutritional regulation of fatty acids and triglycerides in lipogenic organs such as the liver (By similarity). Required for innate immune response in macrophages by regulating lipid metabolism (By similarity).
Isoform SREBP-1C
Predominant isoform expressed in most tissues, which has weaker transcriptional activity compared to isoform SREBP-1A (By similarity). Primarily controls expression of lipogenic gene (PubMed:12177166). Strongly activates global lipid synthesis in rapidly growing cells (By similarity).
Isoform SREBP-1aDelta
The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters.
Isoform SREBP-1cDelta
The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters.
Involvement in disease
IFAP syndrome 2
IFAP2
An autosomal dominant form of IFAP syndrome, a disease characterized by a peculiar triad of follicular ichthyosis, total or subtotal atrichia, and photophobia of varying degree. IFAP2 patients manifest ichthyosis follicularis or follicular hyperkeratosis, hyperkeratotic plaques, sparse to no body hair, and photophobia with punctate corneal epithelial defects, corneal pannus, and complicated cataract. Ultrastructural hair analysis shows trichorrhexis nodosa.
None
The disease is caused by variants affecting the gene represented in this entry.
Mucoepithelial dysplasia, hereditary
HMD
An autosomal dominant genodermatosis mainly characterized by chronic mucosal lesions associated with keratitis, non-scarring alopecia, keratosis pilaris and perineal intertrigo.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Sterol regulatory element-binding protein 1
Processed in the Golgi apparatus, releasing the protein from the membrane (PubMed:32322062, PubMed:8626610). At low cholesterol the SCAP-SREBP complex is recruited into COPII vesicles for export from the endoplasmic reticulum (PubMed:32322062, PubMed:8626610). In the Golgi, complex SREBPs are cleaved sequentially by site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P) protease (PubMed:32322062, PubMed:8626610). 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 (PubMed:32322062).
Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression (By similarity). Phosphorylation at Ser-402 by SIK1 represses activity possibly by inhibiting DNA-binding (By similarity).
Sterol regulatory element-binding protein 1
SCAP-free SREBF1 is ubiquitinated by the BCR(ARMC5) complex, leading to its degradation.
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
Expressed in a wide variety of tissues, most abundant in liver and adrenal gland (PubMed:8402897). In fetal tissues lung and liver shows highest expression (PubMed:8402897).
Isoform SREBP-1A
Predominates in hepatoma cell lines (PubMed:8402897). Also expressed in kidney, brain, white fat, and muscle (PubMed:8402897).
Isoform SREBP-1C
Predominantly expressed in liver and adipose tissues (PubMed:8402897). Also expressed in kidney, brain, white fat, and muscle (PubMed:8402897).
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. 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 1
- Nucleus
- Isoform SREBP-1aDelta
- Nucleus
- Isoform SREBP-1cDelta
- Nucleus
Alternative names
BHLHD1, SREBP1, SREBF1, Sterol regulatory element-binding protein 1, SREBP-1, Class D basic helix-loop-helix protein 1, Sterol regulatory element-binding transcription factor 1, bHLHd1