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Details on Person UniProt:P56720-2 Srebf1

Class:IdReferenceIsoform:154351
_chainChangeLogchain:1-1134 added on Sat February 7 2015;chain:1-480 added on Sat February 7 2015
_displayNameUniProt:P56720-2 Srebf1
_timestamp2025-08-15 21:11:25
chainchain:1-1134
chain:1-480
checksum1D31A9AD3C36AB29
commentFUNCTION Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane (By similarity). 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 (By similarity). Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') (PubMed:7739539). 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 (By similarity).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 (By similarity). Has a role in the nutritional regulation of fatty acids and triglycerides in lipogenic organs such as the liver. 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 (By similarity). Strongly activates global lipid synthesis in rapidly growing cells (By similarity).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 Efficient DNA binding of the soluble transcription factor fragment requires dimerization with another bHLH protein (By similarity). Interacts with CEBPA, the interaction produces a transcriptional synergy. Interacts with LMNA (By similarity).SUBUNIT Forms a tight complex with SCAP, the SCAP-SREBP complex, in the endoplasmic reticulum membrane and the Golgi apparatus. Interacts with PAQR3; the interaction anchors the SCAP-SREBP complex to the Golgi apparatus in low cholesterol conditions.SUBCELLULAR LOCATION 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 Expressed predominantly in brown adipose tissue.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. 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. 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.PTM Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression. Phosphorylation at Ser-395 by SIK1 represses activity possibly by inhibiting DNA-binding.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.SIMILARITY Belongs to the SREBP family.
descriptionrecommendedName: fullName evidence="10"Sterol regulatory element-binding protein 1 shortName evidence="10"SREBP-1 alternativeName: fullName evidence="10"Adipocyte determination- and differentiation-dependent factor 1 shortName evidence="10"ADD1 alternativeName: fullName evidence="10"Sterol regulatory element-binding transcription factor 1 component recommendedName: fullName evidence="12"Processed sterol regulatory element-binding protein 1 alternativeName: fullName evidence="12"Transcription factor SREBF1 /component
geneNameSrebf1
Srebp1
identifierP56720
isoformParent
isSequenceChangedFALSE
keywordActivator
Alternative splicing
Cholesterol metabolism
Cytoplasmic vesicle
DNA-binding
Endoplasmic reticulum
Golgi apparatus
Lipid metabolism
Membrane
Nucleus
Phosphoprotein
Reference proteome
Steroid metabolism
Sterol metabolism
Transcription
Transcription regulation
Transmembrane
Transmembrane helix
Ubl conjugation
modified[InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10
[InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53
[InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12
[InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39
[InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18
[InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35
[InstanceEdit:423310] Kanapin, AA
[InstanceEdit:435478] Kanapin, AA
[InstanceEdit:435871] Kanapin, AA
[InstanceEdit:447347] Kanapin, AA
[InstanceEdit:525883] Kanapin, AA
[InstanceEdit:613449] Kanapin, AA
[InstanceEdit:797602] Kanapin, AA
[InstanceEdit:937368] Yung, CK
[InstanceEdit:1042053] Yung, CK
[InstanceEdit:1220657] Yung, CK
[InstanceEdit:1300696] Yung, CK
[InstanceEdit:1301627] Yung, CK
[InstanceEdit:1551960] Weiser, JD
[InstanceEdit:1995863] Weiser, JD
[InstanceEdit:2132304] Weiser, JD
[InstanceEdit:2265580] Weiser, JD
[InstanceEdit:2587579] Weiser, JD
[InstanceEdit:5433710] Weiser, JD
[InstanceEdit:5618415] Weiser, JD
[InstanceEdit:5634237] Weiser, JD
[InstanceEdit:5673015] Weiser, JD
[InstanceEdit:5691543] Weiser, JD
[InstanceEdit:9037114] Weiser, JD
[InstanceEdit:9637257] Weiser, JD
[InstanceEdit:9657908] Weiser, JD
[InstanceEdit:9676415] Weiser, JD
[InstanceEdit:9698430] Weiser, JD
[InstanceEdit:9715482] Weiser, JD
[InstanceEdit:9730071] Weiser, JD
[InstanceEdit:9750299] Weiser, JD
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9862192] Weiser, Joel, 2024-02-26
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
nameSrebf1
referenceDatabase[ReferenceDatabase:2] UniProt
secondaryIdentifierSRBP1_RAT
Q99PI6
Q99PI7
sequenceLength1134
species[Species:48895] Rattus norvegicus
variantIdentifierP56720-2
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No pathways have been reviewed or authored by UniProt:P56720-2 Srebf1 (154351)