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Details on Person UniProt:P36956 SREBF1
| Class:Id | ReferenceGeneProduct:65046 |
|---|---|
| _chainChangeLog | chain:1-1147 added on Sat February 7 2015;chain:1-490 added on Sat February 7 2015 |
| _displayName | UniProt:P36956 SREBF1 |
| _timestamp | 2025-08-15 21:11:24 |
| chain | chain:1-1147 chain:1-490 |
| checksum | 58F28870739FF259 |
| comment | FUNCTION 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).FUNCTION 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).FUNCTION 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).FUNCTION 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).FUNCTION The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters.FUNCTION The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters.ACTIVITY REGULATION Activation by cleavage is down-regulated upon activation of SIRT3-dependent PRKAA1/AMPK-alpha signaling cascade which leads to inhibition of ATP-consuming lipogenesis to restore cellular energy balance.SUBUNIT Forms a tight complex with SCAP, the SCAP-SREBP complex, in the endoplasmic reticulum membrane and the Golgi apparatus (PubMed:32322062). Interacts with PAQR3; the interaction anchors the SCAP-SREBP complex to the Golgi apparatus in low cholesterol conditions (PubMed:26311497).SUBUNIT Efficient DNA binding of the soluble transcription factor fragment requires dimerization with another bHLH protein (PubMed:8402897). Interacts with CEBPA, the interaction produces a transcriptional synergy (By similarity). Interacts with LMNA (By similarity).INTERACTION 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.SUBCELLULAR LOCATION Additional isoforms seem to exist.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).TISSUE SPECIFICITY Predominates in hepatoma cell lines (PubMed:8402897). Also expressed in kidney, brain, white fat, and muscle (PubMed:8402897).TISSUE SPECIFICITY Predominantly expressed in liver and adipose tissues (PubMed:8402897). Also expressed in kidney, brain, white fat, and muscle (PubMed:8402897).DOMAIN The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.PTM 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).PTM 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).PTM SCAP-free SREBF1 is ubiquitinated by the BCR(ARMC5) complex, leading to its degradation.PTM Ubiquitinated; the nuclear form has a rapid turnover and is rapidly ubiquitinated and degraded by the proteasome in the nucleus.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the SREBP family.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Intron retention.ONLINE INFORMATION Sterol regulatory element-binding protein entry |
| description | recommendedName: fullName evidence="25"Sterol regulatory element-binding protein 1 shortName evidence="25"SREBP-1 alternativeName: Class D basic helix-loop-helix protein 1 shortName: bHLHd1 alternativeName: fullName evidence="25"Sterol regulatory element-binding transcription factor 1 component recommendedName: fullName evidence="26"Processed sterol regulatory element-binding protein 1 alternativeName: fullName evidence="26"Transcription factor SREBF1 /component |
| geneName | SREBF1 BHLHD1 SREBP1 |
| identifier | P36956 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Activator Alternative splicing Cholesterol metabolism Cytoplasmic vesicle Direct protein sequencing Disease variant DNA-binding Endoplasmic reticulum Golgi apparatus Ichthyosis Lipid metabolism Membrane Nucleus Phosphoprotein Proteomics identification Reference proteome Steroid metabolism Sterol metabolism Transcription Transcription regulation Transmembrane Transmembrane helix Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | SREBF1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:5641224] ENSEMBL:ENSG00000072310 SREBF1 [Homo sapiens] |
| secondaryIdentifier | SRBP1_HUMAN B0I4X3 B0I4X4 D3DXC4 Q16062 Q59F52 Q6P4R7 Q6PFW7 Q6PJ36 Q8TAK9 |
| sequenceLength | 1147 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:154346] UniProt:P36956-2 SREBF1 [Homo sapiens] [ReferenceIsoform:154347] UniProt:P36956-3 SREBF1 [Homo sapiens] [ReferenceIsoform:249391] UniProt:P36956-4 SREBF1 [Homo sapiens] [ReferenceIsoform:403893] UniProt:P36956-1 SREBF1 [Homo sapiens] [ReferenceIsoform:8974497] UniProt:P36956-5 SREBF1 [Homo sapiens] [ReferenceIsoform:8974498] UniProt:P36956-6 SREBF1 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:1368141] SREBF1(1-1147) [endoplasmic reticulum membrane] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P36956 SREBF1 (65046)
