SREBF1
Sterol regulatory element-binding protein 1
Also known as: bHLHd1, SRBP1_HUMAN, SREBP-1c, SREBP1, SREBP1a
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P36956
- Gene
- SREBF1
- Ensembl
- ENSG00000072310
- Chromosome
- 17
- Canonical length
- 1147 aa
- Protein class
- Disease related genes, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Transcription factors
- Subcellular location
- Nucleoplasm
OverviewNCBI Gene
This gene encodes a basic helix-loop-helix-leucine zipper (bHLH-Zip) transcription factor that binds to the sterol regulatory element-1 (SRE1), which is a motif that is found in the promoter of the low density lipoprotein receptor gene and other genes involved in sterol biosynthesis. The encoded protein is synthesized as a precursor that is initially attached to the nuclear membrane and endoplasmic reticulum. Following cleavage, the mature protein translocates to the nucleus and activates transcription. This cleaveage is inhibited by sterols. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Alternative promoter usage and splicing result in multiple transcript variants, including SREBP-1a and SREBP-1c, which correspond to RefSeq transcript variants 2 and 3, respectively. [provided by RefSeq, Nov 2017]
Canonical amino-acid sequenceUniProt
1147 residues, UniProt reviewed canonical sequence.
>P36956|SREBF1
1 MDEPPFSEAA LEQALGEPCD LDAALLTDIE DMLQLINNQD SDFPGLFDPP YAGSGAGGTD
61 PASPDTSSPG SLSPPPATLS SSLEAFLSGP QAAPSPLSPP QPAPTPLKMY PSMPAFSPGP
121 GIKEESVPLS ILQTPTPQPL PGALLPQSFP APAPPQFSST PVLGYPSPPG GFSTGSPPGN
181 TQQPLPGLPL ASPPGVPPVS LHTQVQSVVP QQLLTVTAAP TAAPVTTTVT SQIQQVPVLL
241 QPHFIKADSL LLTAMKTDGA TVKAAGLSPL VSGTTVQTGP LPTLVSGGTI LATVPLVVDA
301 EKLPINRLAA GSKAPASAQS RGEKRTAHNA IEKRYRSSIN DKIIELKDLV VGTEAKLNKS
361 AVLRKAIDYI RFLQHSNQKL KQENLSLRTA VHKSKSLKDL VSACGSGGNT DVLMEGVKTE
421 VEDTLTPPPS DAGSPFQSSP LSLGSRGSGS GGSGSDSEPD SPVFEDSKAK PEQRPSLHSR
481 GMLDRSRLAL CTLVFLCLSC NPLASLLGAR GLPSPSDTTS VYHSPGRNVL GTESRDGPGW
541 AQWLLPPVVW LLNGLLVLVS LVLLFVYGEP VTRPHSGPAV YFWRHRKQAD LDLARGDFAQ
601 AAQQLWLALR ALGRPLPTSH LDLACSLLWN LIRHLLQRLW VGRWLAGRAG GLQQDCALRV
661 DASASARDAA LVYHKLHQLH TMGKHTGGHL TATNLALSAL NLAECAGDAV SVATLAEIYV
721 AAALRVKTSL PRALHFLTRF FLSSARQACL AQSGSVPPAM QWLCHPVGHR FFVDGDWSVL
781 STPWESLYSL AGNPVDPLAQ VTQLFREHLL ERALNCVTQP NPSPGSADGD KEFSDALGYL
841 QLLNSCSDAA GAPAYSFSIS SSMATTTGVD PVAKWWASLT AVVIHWLRRD EEAAERLCPL
901 VEHLPRVLQE SERPLPRAAL HSFKAARALL GCAKAESGPA SLTICEKASG YLQDSLATTP
961 ASSSIDKAVQ LFLCDLLLVV RTSLWRQQQP PAPAPAAQGT SSRPQASALE LRGFQRDLSS
1021 LRRLAQSFRP AMRRVFLHEA TARLMAGASP TRTHQLLDRS LRRRAGPGGK GGAVAELEPR
1081 PTRREHAEAL LLASCYLPPG FLSAPGQRVG MLAEAARTLE KLGDRRLLHD CQQMLMRLGG
1141 GTTVTSSLocalizationUniProt · AlphaFold · HPA
Whether an antibody against SREBF1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Other membrane
- Secreted
- No
- Transmembrane segments
- 2
- Mean surface accessibility (rSASA)
- 0.45
- Highest tissue expression
- 150 nTPM
Expression across tissuesHPA
Tissue
- adrenal gland: 150 nTPM
- liver: 114 nTPM
- salivary gland: 85 nTPM
- esophagus: 53 nTPM
- adipose tissue: 40 nTPM
- vagina: 35 nTPM
Single-cell type
- adrenal cortex cells: 274 nCPM
- breast lactating cells: 221 nCPM
- urothelial cells: 160 nCPM
- esophageal suprabasal cells: 135 nCPM
- astrocytes: 127 nCPM
- pituicytes/fscs: 116 nCPM
Immune cell
- neutrophil: 1.3 nTPM
- naive CD8 T-cell: 0.6 nTPM
- gdT-cell: 0.4 nTPM
- naive CD4 T-cell: 0.4 nTPM
- classical monocyte: 0.3 nTPM
- memory CD4 T-cell: 0.2 nTPM
Brain region
- cerebral cortex: 116 nTPM
- basal ganglia: 109 nTPM
- white matter: 108 nTPM
- thalamus: 98 nTPM
- medulla oblongata: 88 nTPM
- midbrain: 87 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about SREBF1.
Disease | AllUniProt
Conditions SREBF1 is implicated in, by any mechanism.
- IFAP syndrome 2 (IFAP2) MIM:619016
- Mucoepithelial dysplasia, hereditary (HMD) MIM:158310
Disease | GeneticClinVar
6 pathogenic / likely-pathogenic of 233 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Hereditary mucoepithelial dysplasia
- IFAP syndrome 1, with or without BRESHECK syndrome
- IFAP syndrome 2
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.45
- gnomAD pLI
- 0.01
- gnomAD missense Z
- 1.98
- DepMap mean gene effect
- -0.34
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cellular response to fatty acid
- cellular response to starvation
- cholesterol biosynthetic process
- circadian rhythm
- fat cell differentiation
- insulin receptor signaling pathway
- insulin secretion
- lipid biosynthetic process
- lipid metabolic process
- lung development
- mRNA transcription by RNA polymerase II
- negative regulation of insulin secretion
- negative regulation of transcription by RNA polymerase II
- negative regulation of triglyceride metabolic process
- positive regulation of cholesterol biosynthetic process
- positive regulation of miRNA transcription
- positive regulation of transcription by RNA polymerase II
- positive regulation of triglyceride biosynthetic process
- regulation of fatty acid metabolic process
- regulation of heart rate by chemical signal
- regulation of mitophagy
- regulation of protein stability
- regulation of protein targeting to mitochondrion
- regulation of transcription by RNA polymerase II
- response to cAMP
- response to ethanol
- response to food
- response to fructose
- response to glucagon
- response to glucose
- response to nutrient
- response to progesterone
- response to retinoic acid
- response to xenobiotic stimulus
- SREBP signaling pathway
Molecular functions
- chromatin binding
- DNA binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- nuclear receptor activity
- protein dimerization activity
- protein kinase binding
- protein-containing complex binding
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- RNA polymerase II transcription regulatory region sequence-specific DNA binding
- sequence-specific double-stranded DNA binding
- sterol response element binding
- transcription coregulator binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of SREBF1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads SREBF1 as an antibody target. Whether an autoantibody or antibody against SREBF1 could matter depends on whether native SREBF1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
SREBF1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label SREBF1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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