LEF1
Lymphoid enhancer-binding factor 1
Also known as: LEF1_HUMAN, TCF10, TCF1ALPHA, TCF7L3
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9UJU2
- Gene
- LEF1
- Ensembl
- ENSG00000138795
- Chromosome
- 4
- Canonical length
- 399 aa
- Protein class
- Cancer-related genes, Plasma proteins, Predicted intracellular proteins, Transcription factors
- Subcellular location
- Nucleoplasm
OverviewNCBI Gene
This gene encodes a transcription factor belonging to a family of proteins that share homology with the high mobility group protein-1. The protein encoded by this gene can bind to a functionally important site in the T-cell receptor-alpha enhancer, thereby conferring maximal enhancer activity. This transcription factor is involved in the Wnt signaling pathway, and it may function in hair cell differentiation and follicle morphogenesis. Mutations in this gene have been found in somatic sebaceous tumors. This gene has also been linked to other cancers, including androgen-independent prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
Canonical amino-acid sequenceUniProt
399 residues, UniProt reviewed canonical sequence.
>Q9UJU2|LEF1
1 MPQLSGGGGG GGGDPELCAT DEMIPFKDEG DPQKEKIFAE ISHPEEEGDL ADIKSSLVNE
61 SEIIPASNGH EVARQAQTSQ EPYHDKAREH PDDGKHPDGG LYNKGPSYSS YSGYIMMPNM
121 NNDPYMSNGS LSPPIPRTSN KVPVVQPSHA VHPLTPLITY SDEHFSPGSH PSHIPSDVNS
181 KQGMSRHPPA PDIPTFYPLS PGGVGQITPP LGWQGQPVYP ITGGFRQPYP SSLSVDTSMS
241 RFSHHMIPGP PGPHTTGIPH PAIVTPQVKQ EHPHTDSDLM HVKPQHEQRK EQEPKRPHIK
301 KPLNAFMLYM KEMRANVVAE CTLKESAAIN QILGRRWHAL SREEQAKYYE LARKERQLHM
361 QLYPGWSARD NYGKKKKRKR EKLQESASGT GPRMTAAYILocalizationUniProt · AlphaFold · HPA
Whether an antibody against LEF1 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
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.65
- Highest tissue expression
- 325 nTPM
Expression across tissuesHPA
Tissue
- thymus: 325 nTPM
- lymph node: 29 nTPM
- tonsil: 21 nTPM
- appendix: 13 nTPM
- adrenal gland: 12 nTPM
- testis: 12 nTPM
Single-cell type
- thymocytes: 347 nCPM
- choroid plexus epithelial cells: 265 nCPM
- renal collecting duct intercalated cells: 256 nCPM
- melanocytes: 214 nCPM
- t-cells: 142 nCPM
- ependymal cells: 108 nCPM
Immune cell
- naive CD4 T-cell: 143 nTPM
- naive CD8 T-cell: 103 nTPM
- T-reg: 98 nTPM
- memory CD4 T-cell: 69 nTPM
- total PBMC: 37 nTPM
- NK-cell: 33 nTPM
Brain region
- thalamus: 42 nTPM
- choroid plexus: 33 nTPM
- midbrain: 26 nTPM
- amygdala: 25 nTPM
- hypothalamus: 23 nTPM
- pons: 22 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about LEF1.
Disease | AllUniProt
Conditions LEF1 is implicated in, by any mechanism.
- Ectodermal dysplasia 17 with or without limb malformations (ECTD17) MIM:621224
Disease | GeneticClinVar
7 pathogenic / likely-pathogenic of 77 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Ectodermal dysplasia 17 with or without limb malformations
- Ectrodactyly
- Ectrodactyly and ectodermal dysplasia without cleft lip/palate
- LEF1-related ectodermal dysplasia
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)
- 0.21
- gnomAD pLI
- 1
- gnomAD missense Z
- 1.57
- DepMap mean gene effect
- -0.06
- 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
- anatomical structure regression
- apoptotic process involved in blood vessel morphogenesis
- B cell proliferation
- BMP signaling pathway
- branching involved in blood vessel morphogenesis
- canonical Wnt signaling pathway
- cell chemotaxis
- cellular response to cytokine stimulus
- cellular response to interleukin-4
- chorio-allantoic fusion
- dentate gyrus development
- embryonic limb morphogenesis
- epithelial cell apoptotic process
- epithelial to mesenchymal transition
- face morphogenesis
- forebrain neuroblast division
- forebrain radial glial cell differentiation
- formation of radial glial scaffolds
- host-mediated activation of viral transcription
- mammary gland development
- negative regulation of apoptotic process
- negative regulation of apoptotic process in bone marrow cell
- negative regulation of DNA binding
- negative regulation of DNA-templated transcription
- negative regulation of interleukin-13 production
- negative regulation of interleukin-4 production
- negative regulation of interleukin-5 production
- negative regulation of striated muscle tissue development
- negative regulation of transcription by RNA polymerase II
- neutrophil differentiation
- odontogenesis of dentin-containing tooth
- osteoblast differentiation
- paraxial mesoderm formation
- positive regulation of cell cycle process
- positive regulation of cell differentiation
- positive regulation of cell migration
- positive regulation of cell proliferation in bone marrow
- positive regulation of chondrocyte proliferation
- positive regulation of DNA-templated transcription
- positive regulation of endothelial cell-matrix adhesion via fibronectin
- positive regulation of epithelial to mesenchymal transition
- positive regulation of gamma-delta T cell differentiation
- positive regulation of gene expression
- positive regulation of granulocyte differentiation
- positive regulation of odontoblast differentiation
- positive regulation of transcription by RNA polymerase II
- positive regulation of Wnt signaling pathway
- protein localization to chromatin
- regulation of neurogenesis
- regulation of transcription by RNA polymerase II
- secondary palate development
- sensory perception of taste
- somitogenesis
- sprouting angiogenesis
- T cell receptor V(D)J recombination
- T-helper 1 cell differentiation
- tongue development
- trachea gland development
- transcription by RNA polymerase II
Molecular functions
- armadillo repeat domain binding
- beta-catenin binding
- C2H2 zinc finger domain binding
- chromatin binding
- DNA binding
- DNA binding, bending
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- gamma-catenin binding
- histone deacetylase binding
- nuclear estrogen receptor binding
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- RNA polymerase II transcription regulatory region sequence-specific DNA binding
- sequence-specific DNA binding
- sequence-specific double-stranded DNA binding
- transcription corepressor binding
- transcription regulator inhibitor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of LEF1 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 LEF1 as an antibody target. Whether an autoantibody or antibody against LEF1 could matter depends on whether native LEF1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
LEF1 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 LEF1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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