{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9UL17","uniProtkbId":"TBX21_HUMAN","entryAudit":{"firstPublicDate":"2001-01-11","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2000-05-01","entryVersion":191,"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":{"value":"T-box transcription factor TBX21"},"shortNames":[{"value":"T-box protein 21"}]},"alternativeNames":[{"fullName":{"value":"T-cell-specific T-box transcription factor T-bet"}},{"fullName":{"value":"Transcription factor TBLYM"}}]},"genes":[{"geneName":{"value":"TBX21"},"synonyms":[{"value":"TBET"},{"value":"TBLYM"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9JKD8"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10761931"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27292648"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33296702"}],"value":"Lineage-defining transcription factor which initiates Th1 lineage development from naive Th precursor cells both by activating Th1 genetic programs and by repressing the opposing Th2 and Th17 genetic programs (PubMed:10761931). Activates transcription of a set of genes important for Th1 cell function, including those encoding IFN-gamma and the chemokine receptor CXCR3. Induces permissive chromatin accessibility and CpG methylation in IFNG (PubMed:33296702). Activates IFNG and CXCR3 genes in part by recruiting chromatin remodeling complexes including KDM6B, a SMARCA4-containing SWI/SNF-complex, and an H3K4me2-methyltransferase complex to their promoters and all of these complexes serve to establish a more permissive chromatin state conducive with transcriptional activation (By similarity). Can activate Th1 genes also via recruitment of Mediator complex and P-TEFb (composed of CDK9 and CCNT1/cyclin-T1) in the form of the super elongation complex (SEC) to super-enhancers and associated genes in activated Th1 cells (PubMed:27292648). Inhibits the Th17 cell lineage commitment by blocking RUNX1-mediated transactivation of Th17 cell-specific transcriptinal regulator RORC. Inhibits the Th2 cell lineage commitment by suppressing the production of Th2 cytokines, such as IL-4, IL-5, and IL- 13, via repression of transcriptional regulators GATA3 and NFATC2. Protects Th1 cells from amplifying aberrant type-I IFN response in an IFN-gamma abundant microenvironment by acting as a repressor of type-I IFN transcription factors and type-I IFN-stimulated genes. Acts as a regulator of antiviral B-cell responses; controls chronic viral infection by promoting the antiviral antibody IgG2a isotype switching and via regulation of a broad antiviral gene expression program (By similarity). Required for the correct development of natural killer (NK) and mucosal-associated invariant T (MAIT) cells (PubMed:33296702)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9JKD8"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15662016"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24845384"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27292648"}],"value":"Interacts with RUNX1, RUNX3, ITK, ABL1, RELA, CDK9 and KDM6B. The phosphorylated form (at Thr-303) interacts with NFATC2. Interacts with SMARCA4 in a KDM6B-dependent manner (By similarity). Interacts with CCTN1 (PubMed:27292648). Interacts with USP10 (PubMed:24845384). The phosphorylated form (at Tyr-530) interacts with GATA3 (PubMed:15662016)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q9UL17","intActId":"EBI-3922312"},"interactantTwo":{"uniProtKBAccession":"Q92793","geneName":"CREBBP","intActId":"EBI-81215"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UL17","intActId":"EBI-3922312"},"interactantTwo":{"uniProtKBAccession":"Q09472","geneName":"EP300","intActId":"EBI-447295"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UL17","intActId":"EBI-3922312"},"interactantTwo":{"uniProtKBAccession":"P23771","geneName":"GATA3","intActId":"EBI-6664760"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q9UL17","intActId":"EBI-3922312"},"interactantTwo":{"uniProtKBAccession":"P08047","geneName":"SP1","intActId":"EBI-298336"},"numberOfExperiments":4,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24845384"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33296702"}],"value":"Nucleus","id":"SL-0191"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10761931"}],"value":"T-cell specific"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9JKD8"}],"value":"Phosphorylations at Ser-53, Tyr-77, Ser-225 and Ser-513 are regulated by mTORC1. 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Deubiquitinated by USP10 leading to its stabilization (PubMed:24845384)"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Asthma, with nasal polyps and aspirin intolerance","diseaseAccession":"DI-02739","acronym":"ANPAI","description":"A condition consisting of asthma, aspirin sensitivity and nasal polyposis. 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