{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9UJU2","secondaryAccessions":["B4DG38","B7Z8E2","E9PDK3","Q3ZCU4","Q9HAZ0"],"uniProtkbId":"LEF1_HUMAN","entryAudit":{"firstPublicDate":"2000-12-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2000-05-01","entryVersion":222,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:6551"}],"value":"Lymphoid enhancer-binding factor 1"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"10756202"}],"value":"LEF-1"}]},"alternativeNames":[{"fullName":{"value":"T cell-specific transcription factor 1-alpha"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:6551"}],"value":"TCF1-alpha"}]}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:6551"}],"value":"LEF1"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P27782"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11266540"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19653274"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"2010090"}],"value":"Transcription factor that binds DNA in a sequence-specific manner (PubMed:2010090). Participates in the Wnt signaling pathway (By similarity). Activates transcription of target genes in the presence of CTNNB1 and EP300 (By similarity). PIAG antagonizes both Wnt-dependent and Wnt-independent activation by LEF1 (By similarity). TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by LEF1 and CTNNB1 (PubMed:11266540). Regulates T-cell receptor alpha enhancer function (PubMed:19653274). Required for IL17A expressing gamma-delta T-cell maturation and development, via binding to regulator loci of BLK to modulate expression (By similarity). Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, expression is repressed during the bell stage by MSX1-mediated inhibition of CTNNB1 signaling (By similarity). May play a role in hair cell differentiation and follicle morphogenesis (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19653274"}],"value":"Transcriptionally activates MYC and CCND1 expression and enhances proliferation of pancreatic tumor cells"}],"commentType":"FUNCTION","molecule":"Isoform 1"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11326276"}],"value":"Lacks the CTNNB1 interaction domain and may therefore be an antagonist for Wnt signaling"}],"commentType":"FUNCTION","molecule":"Isoform 3"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19653274"}],"value":"Transcriptionally activates the fibronectin promoter, binds to and represses transcription from the E-cadherin promoter in a CTNNB1-independent manner, and is involved in reducing cellular aggregation and increasing cell migration of pancreatic cancer cells"}],"commentType":"FUNCTION","molecule":"Isoform 5"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P27782"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12192039"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12556497"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19304756"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9119228"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9488439"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9751710"}],"value":"Binds the armadillo repeat of CTNNB1 and forms a stable complex. Interacts with EP300, TLE1 and PIASG (By similarity). Binds ALYREF/THOC4, MDFI and MDFIC. Interacts with NLK. Interacts with DAZAP2 (PubMed:19304756)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q9UJU2","intActId":"EBI-926131"},"interactantTwo":{"uniProtKBAccession":"P35222","geneName":"CTNNB1","intActId":"EBI-491549"},"numberOfExperiments":10,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UJU2","intActId":"EBI-926131"},"interactantTwo":{"uniProtKBAccession":"P49789","geneName":"FHIT","intActId":"EBI-741760"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UJU2","intActId":"EBI-926131"},"interactantTwo":{"uniProtKBAccession":"P08069","geneName":"IGF1R","intActId":"EBI-475981"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UJU2","intActId":"EBI-926131"},"interactantTwo":{"uniProtKBAccession":"Q16236","geneName":"NFE2L2","intActId":"EBI-2007911"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UJU2","intActId":"EBI-926131"},"interactantTwo":{"uniProtKBAccession":"Q96LA8","geneName":"PRMT6","intActId":"EBI-912440"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"Found in nuclear bodies upon PIASG binding"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00267"}],"value":"Nucleus","id":"SL-0191"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative promoter usage","Alternative splicing"],"isoforms":[{"name":{"value":"1"},"synonyms":[{"value":"A"}],"isoformIds":["Q9UJU2-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"synonyms":[{"value":"B"},{"value":"8A"}],"isoformIds":["Q9UJU2-2"],"sequenceIds":["VSP_002188"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"synonyms":[{"value":"LEF-1-DN"}],"isoformIds":["Q9UJU2-3"],"sequenceIds":["VSP_007022"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"isoformIds":["Q9UJU2-4"],"sequenceIds":["VSP_007022","VSP_002188"],"isoformSequenceStatus":"Described"},{"name":{"value":"5"},"isoformIds":["Q9UJU2-5"],"sequenceIds":["VSP_040068"],"isoformSequenceStatus":"Described"},{"name":{"value":"6"},"isoformIds":["Q9UJU2-6"],"sequenceIds":["VSP_040068","VSP_040069"],"isoformSequenceStatus":"Described"},{"name":{"value":"7"},"isoformIds":["Q9UJU2-7"],"sequenceIds":["VSP_044877","VSP_040068"],"isoformSequenceStatus":"Described"}],"note":{"texts":[{"value":"Additional isoforms seem to exist."}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19653274"}],"value":"Detected in thymus. Not detected in normal colon, but highly expressed in colon cancer biopsies and colon cancer cell lines. Expressed in several pancreatic tumors and weakly expressed in normal pancreatic tissue. Isoforms 1 and 5 are detected in several pancreatic cell lines"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"value":"Proline-rich and acidic regions are implicated in the activation functions of RNA polymerase II transcription factors"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12556497"}],"value":"Phosphorylated at Thr-155 and/or Ser-166 by NLK. Phosphorylation by NLK at these sites represses LEF1-mediated transcriptional activation of target genes of the canonical Wnt signaling pathway"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Ectodermal dysplasia 17 with or without limb malformations","diseaseAccession":"DI-07042","acronym":"ECTD17","description":"A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ECTD17 is an autosomal dominant form characterized by hypohidrosis, dry skin, hair and tooth anomalies, and slow nail growth. Some patients have limb abnormalities such as radial ray defects, polydactyly, syndactyly, and split hand/foot malformation.","diseaseCrossReference":{"database":"MIM","id":"621224"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35583550"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"39107921"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"value":"Produced by alternative promoter usage"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 1"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Produced by alternative splicing of isoform 1. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 2"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Produced by alternative promoter usage. Acts as a dominant negative mutant"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 3"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Produced by alternative splicing of isoform 3"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 4"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Produced by alternative splicing of isoform 1"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 5"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Produced by alternative splicing of isoform 1"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 6"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the TCF/LEF family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":399,"modifier":"EXACT"}},"description":"Lymphoid enhancer-binding factor 1","featureId":"PRO_0000048595"},{"type":"DNA binding","location":{"start":{"value":299,"modifier":"EXACT"},"end":{"value":367,"modifier":"EXACT"}},"description":"HMG box","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00267"}]},{"type":"Region","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":104,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":62,"modifier":"EXACT"}},"description":"CTNNB1-binding","evidences":[{"evidenceCode":"ECO:0000250"}]},{"type":"Region","location":{"start":{"value":166,"modifier":"EXACT"},"end":{"value":192,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":268,"modifier":"EXACT"},"end":{"value":298,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":369,"modifier":"EXACT"},"end":{"value":399,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":14,"modifier":"EXACT"}},"description":"Gly residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":24,"modifier":"EXACT"},"end":{"value":45,"modifier":"EXACT"}},"description":"Basic and acidic residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":82,"modifier":"EXACT"},"end":{"value":98,"modifier":"EXACT"}},"description":"Basic and acidic residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":269,"modifier":"EXACT"},"end":{"value":296,"modifier":"EXACT"}},"description":"Basic and acidic residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Modified residue","location":{"start":{"value":132,"modifier":"EXACT"},"end":{"value":132,"modifier":"EXACT"}},"description":"Phosphoserine","evidences":[{"evidenceCode":"ECO:0007744","source":"PubMed","id":"19690332"}]},{"type":"Modified residue","location":{"start":{"value":155,"modifier":"EXACT"},"end":{"value":155,"modifier":"EXACT"}},"description":"Phosphothreonine; 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