SREBF1

This gene encodes a transcription factor that binds to the sterol regulatory element-1 (SRE1), which is a decamer flanking the low density lipoprotein receptor gene and some genes involved in sterol biosynthesis. The protein is synthesized as a precursor that is attached to the nuclear membrane and endoplasmic reticulum. Following cleavage, the mature protein translocates to the nucleus and activates transcription by binding to the SRE1. Sterols inhibit the cleavage of the precursor, and the mature nuclear form is rapidly catabolized, thereby reducing transcription. The protein is a member of the basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor family. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq]

sterol regulatory element binding transcription factor 1

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:8402897, PubMed:12177166, PubMed:32322062).
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:8402897, PubMed:12177166).
Regulates the promoters of genes involved in cholesterol biosynthesis and the LDL receptor (LDLR) pathway of sterol regulation (PubMed:8402897, PubMed:12177166, PubMed:32322062).
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.

Biological Process agingIEA:Ensembl
Biological Process cellular response to fatty acidIEA:Ensembl
Biological Process cellular response to starvationBy SimilarityISS:HGNC-UCL
Biological Process cholesterol biosynthetic processIEA:Ensembl
Biological Process circadian rhythmIEA:Ensembl
Biological Process fat cell differentiationIEA:Ensembl
Biological Process insulin receptor signaling pathwayIEA:Ensembl
Biological Process insulin secretionIEA:Ensembl
Biological Process lipid biosynthetic processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process lipid localizationIEA:Ensembl
Biological Process lipid metabolic processManual Assertion Based On ExperimentTAS:ProtInc
Biological Process lung developmentIEA:Ensembl
Biological Process mRNA transcription by RNA polymerase IIIEA:Ensembl
Biological Process negative regulation of insulin secretionIEA:Ensembl
Biological Process negative regulation of transcription by RNA polymerase IIIEA:Ensembl
Biological Process positive regulation of cholesterol biosynthetic processIDA:UniProtKB
Biological Process positive regulation of histone deacetylationIEA:Ensembl
Biological Process positive regulation of miRNA transcriptionManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process positive regulation of triglyceride biosynthetic processISS:UniProtKB
Biological Process regulation of autophagy of mitochondrionManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Biological Process regulation of fatty acid metabolic processIEA:Ensembl
Biological Process regulation of heart rate by chemical signalIEA:Ensembl
Biological Process regulation of lipid storageIEA:Ensembl
Biological Process regulation of protein stabilityManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Biological Process regulation of protein targeting to mitochondrionManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Biological Process regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process response to cAMPIEA:Ensembl
Biological Process response to ethanolIEA:Ensembl
Biological Process response to foodIEA:Ensembl
Biological Process response to glucagonIEA:Ensembl
Biological Process response to glucoseIEA:Ensembl
Biological Process response to progesteroneIEA:Ensembl
Biological Process response to retinoic acidIEA:Ensembl
Biological Process response to xenobiotic stimulusIEA:Ensembl
Biological Process SREBP signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB

Sterol regulatory element-binding protein 1
Endoplasmic reticulum membrane
Golgi apparatus membrane
Cytoplasmic vesicle, COPII-coated vesicle membrane
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

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.
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.

Cytoplasmic: 1-487
Helical: 488-508
Lumenal: 509-547
Helical: 548-568
Cytoplasmic: 569-1147

Sterol regulatory element-binding protein 1
Processed in the Golgi apparatus, releasing the protein from the membrane (PubMed:8626610, PubMed:32322062).
At low cholesterol the SCAP-SREBP complex is recruited into COPII vesicles for export from the endoplasmic reticulum (PubMed:8626610, PubMed:32322062).
In the Golgi, complex SREBPs are cleaved sequentially by site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P) protease (PubMed:8626610, PubMed:32322062).
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).
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.