TBX21_MOUSE
ID TBX21_MOUSE Reviewed; 530 AA.
AC Q9JKD8; Q3U150; Q9R0A6;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=T-box transcription factor TBX21;
DE Short=T-box protein 21;
DE AltName: Full=T-cell-specific T-box transcription factor T-bet;
DE AltName: Full=Transcription factor TBLYM;
GN Name=Tbx21; Synonyms=Tbet, Tblym;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=10761931; DOI=10.1016/s0092-8674(00)80702-3;
RA Szabo S.J., Kim S.T., Costa G.L., Zhang X., Fathman C.G., Glimcher L.H.;
RT "A novel transcription factor, T-bet, directs Th1 lineage commitment.";
RL Cell 100:655-669(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ;
RX PubMed=11087660; DOI=10.1006/geno.2000.6361;
RA Zhang W.X., Yang S.Y.;
RT "Cloning and characterization of a new member of the T-box gene family.";
RL Genomics 70:41-48(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD; TISSUE=Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, INTERACTION WITH GATA3 AND ITK, INDUCTION, SUBCELLULAR LOCATION,
RP PHOSPHORYLATION AT TYR-525, AND MUTAGENESIS OF TYR-437 AND TYR-525.
RX PubMed=15662016; DOI=10.1126/science.1103336;
RA Hwang E.S., Szabo S.J., Schwartzberg P.L., Glimcher L.H.;
RT "T helper cell fate specified by kinase-mediated interaction of T-bet with
RT GATA-3.";
RL Science 307:430-433(2005).
RN [7]
RP FUNCTION.
RX PubMed=17923685; DOI=10.1128/mcb.01615-07;
RA Lewis M.D., Miller S.A., Miazgowicz M.M., Beima K.M., Weinmann A.S.;
RT "T-bet's ability to regulate individual target genes requires the conserved
RT T-box domain to recruit histone methyltransferase activity and a separate
RT family member-specific transactivation domain.";
RL Mol. Cell. Biol. 27:8510-8521(2007).
RN [8]
RP FUNCTION, AND INTERACTION WITH KDM6B AND SMARCA4.
RX PubMed=21095589; DOI=10.1016/j.molcel.2010.10.028;
RA Miller S.A., Mohn S.E., Weinmann A.S.;
RT "Jmjd3 and UTX play a demethylase-independent role in chromatin remodeling
RT to regulate T-box family member-dependent gene expression.";
RL Mol. Cell 40:594-605(2010).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ABL1 AND GATA3,
RP PHOSPHORYLATION AT TYR-219; TYR-265 AND TYR-304, AND MUTAGENESIS OF
RP TYR-219; TYR-265 AND TYR-304.
RX PubMed=21690296; DOI=10.1128/mcb.05383-11;
RA Chen A., Lee S.M., Gao B., Shannon S., Zhu Z., Fang D.;
RT "c-Abl-mediated tyrosine phosphorylation of the T-bet DNA-binding domain
RT regulates CD4+ T-cell differentiation and allergic lung inflammation.";
RL Mol. Cell. Biol. 31:3445-3456(2011).
RN [10]
RP FUNCTION, INTERACTION WITH RUNX1 AND RUNX3, MUTAGENESIS OF TYR-265;
RP TYR-304; SER-508 AND TYR-525, AND SITE.
RX PubMed=21151104; DOI=10.1038/ni.1969;
RA Lazarevic V., Chen X., Shim J.H., Hwang E.S., Jang E., Bolm A.N., Oukka M.,
RA Kuchroo V.K., Glimcher L.H.;
RT "T-bet represses T(H)17 differentiation by preventing Runx1-mediated
RT activation of the gene encoding RORgammat.";
RL Nat. Immunol. 12:96-104(2011).
RN [11]
RP FUNCTION, UBIQUITINATION AT LYS-313, MUTAGENESIS OF LYS-208; THR-302;
RP THR-310; LYS-313 AND LYS-321, PHOSPHORYLATION AT THR-302, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH GATA3; RELA AND NFATC2.
RX PubMed=23616576; DOI=10.4049/jimmunol.1203403;
RA Jang E.J., Park H.R., Hong J.H., Hwang E.S.;
RT "Lysine 313 of T-box is crucial for modulation of protein stability, DNA
RT binding, and threonine phosphorylation of T-bet.";
RL J. Immunol. 190:5764-5770(2013).
RN [12]
RP FUNCTION, AND INTERACTION WITH CCNT1 AND CDK9.
RX PubMed=27292648; DOI=10.1016/j.celrep.2016.05.054;
RA Hertweck A., Evans C.M., Eskandarpour M., Lau J.C., Oleinika K.,
RA Jackson I., Kelly A., Ambrose J., Adamson P., Cousins D.J., Lavender P.,
RA Calder V.L., Lord G.M., Jenner R.G.;
RT "T-bet activates Th1 genes through mediator and the super elongation
RT complex.";
RL Cell Rep. 15:2756-2770(2016).
RN [13]
RP FUNCTION.
RX PubMed=27430722; DOI=10.4049/jimmunol.1500368;
RA Barnett B.E., Staupe R.P., Odorizzi P.M., Palko O., Tomov V.T., Mahan A.E.,
RA Gunn B., Chen D., Paley M.A., Alter G., Reiner S.L., Lauer G.M.,
RA Teijaro J.R., Wherry E.J.;
RT "Cutting Edge: B cell-intrinsic T-bet expression is required to control
RT chronic viral infection.";
RL J. Immunol. 197:1017-1022(2016).
RN [14]
RP FUNCTION.
RX PubMed=28623086; DOI=10.1016/j.immuni.2017.05.005;
RA Iwata S., Mikami Y., Sun H.W., Brooks S.R., Jankovic D., Hirahara K.,
RA Onodera A., Shih H.Y., Kawabe T., Jiang K., Nakayama T., Sher A.,
RA O'Shea J.J., Davis F.P., Kanno Y.;
RT "The transcription factor T-bet limits amplification of Type I IFN
RT transcriptome and circuitry in T helper 1 cells.";
RL Immunity 46:983-991(2017).
RN [15]
RP PHOSPHORYLATION AT SER-52; THR-55; TYR-76; TYR-117; SER-224 AND SER-508,
RP AND MUTAGENESIS OF SER-52; THR-55; TYR-76; TYR-117; SER-224 AND SER-508.
RX PubMed=28424242; DOI=10.4049/jimmunol.1601078;
RA Chornoguz O., Hagan R.S., Haile A., Arwood M.L., Gamper C.J., Banerjee A.,
RA Powell J.D.;
RT "mTORC1 Promotes T-bet phosphorylation to regulate Th1 differentiation.";
RL J. Immunol. 198:3939-3948(2017).
RN [16]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28607488; DOI=10.1038/nature22360;
RA Levine A.G., Medoza A., Hemmers S., Moltedo B., Niec R.E., Schizas M.,
RA Hoyos B.E., Putintseva E.V., Chaudhry A., Dikiy S., Fujisawa S.,
RA Chudakov D.M., Treuting P.M., Rudensky A.Y.;
RT "Stability and function of regulatory T cells expressing the transcription
RT factor T-bet.";
RL Nature 546:421-425(2017).
CC -!- FUNCTION: Lineage-defining transcription factor which initiates Th1
CC lineage development from naive Th precursor cells both by activating
CC Th1 genetic programs and by repressing the opposing Th2 and Th17
CC genetic programs. Activates transcription of a set of genes important
CC for Th1 cell function, including those encoding IFN-gamma and the
CC chemokine receptor CXCR3. Activates IFNG and CXCR3 genes in part by
CC recruiting chromatin remodeling complexes including KDM6B, a SMARCA4-
CC containing SWI/SNF-complex, and an H3K4me2-methyltransferase complex to
CC their promoters and all of these complexes serve to establish a more
CC permissive chromatin state conducive with transcriptional activation
CC (PubMed:10761931, PubMed:17923685, PubMed:21095589). Can activate Th1
CC genes also via recruitment of Mediator complex and P-TEFb (composed of
CC CDK9 and CCNT1/cyclin-T1) in the form of the super elongation complex
CC (SEC) to super-enhancers and associated genes in activated Th1 cells
CC (PubMed:27292648). Inhibits the Th17 cell lineage commitment by
CC blocking RUNX1-mediated transactivation of Th17 cell-specific
CC transcriptinal regulator RORC (PubMed:21151104). Inhibits the Th2 cell
CC lineage commitment by suppressing the production of Th2 cytokines, such
CC as IL-4, IL-5, and IL- 13, via repression of transcriptional regulators
CC GATA3 and NFATC2 (PubMed:15662016, PubMed:21690296, PubMed:23616576).
CC Protects Th1 cells from amplifying aberrant type-I IFN response in an
CC IFN-gamma abundant microenvironment by acting as a repressor of type-I
CC IFN transcription factors and type-I IFN- stimulated genes
CC (PubMed:28623086). Acts as a regulator of antiviral B-cell responses;
CC controls chronic viral infection by promoting the antiviral antibody
CC IgG2a isotype switching and via regulation of a broad antiviral gene
CC expression program (PubMed:27430722). {ECO:0000269|PubMed:10761931,
CC ECO:0000269|PubMed:15662016, ECO:0000269|PubMed:17923685,
CC ECO:0000269|PubMed:21095589, ECO:0000269|PubMed:21151104,
CC ECO:0000269|PubMed:21690296, ECO:0000269|PubMed:23616576,
CC ECO:0000269|PubMed:27292648, ECO:0000269|PubMed:27430722,
CC ECO:0000269|PubMed:28607488, ECO:0000269|PubMed:28623086}.
CC -!- SUBUNIT: Interacts with RUNX1 and RUNX3 (PubMed:21151104). Interacts
CC with ITK (PubMed:15662016). The phosphorylated form (at Tyr-525)
CC interacts with GATA3 (PubMed:15662016, PubMed:21690296,
CC PubMed:23616576). Interacts with ABL1 (PubMed:21690296). Interacts with
CC RELA (PubMed:23616576). The phosphorylated form (at Thr-302) interacts
CC with NFATC2 (PubMed:23616576). Interacts with KDM6B (PubMed:21095589).
CC Interacts with SMARCA4 in a KDM6B-dependent manner (PubMed:21095589).
CC Interacts with CCTN1 and CDK9 (PubMed:27292648). Interacts with USP10
CC (By similarity). {ECO:0000250|UniProtKB:Q9UL17,
CC ECO:0000269|PubMed:15662016, ECO:0000269|PubMed:21095589,
CC ECO:0000269|PubMed:21151104, ECO:0000269|PubMed:21690296,
CC ECO:0000269|PubMed:23616576, ECO:0000269|PubMed:27292648}.
CC -!- INTERACTION:
CC Q9JKD8; P41183: Bcl6; NbExp=3; IntAct=EBI-3863870, EBI-6253762;
CC Q9JKD8; Q03347: Runx1; NbExp=3; IntAct=EBI-3863870, EBI-3863873;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10761931,
CC ECO:0000269|PubMed:15662016, ECO:0000269|PubMed:21690296,
CC ECO:0000269|PubMed:23616576}.
CC -!- TISSUE SPECIFICITY: T-cell specific (PubMed:10761931, PubMed:11087660).
CC Expressed in regulatory T (TReg) cells (PubMed:28607488).
CC {ECO:0000269|PubMed:10761931, ECO:0000269|PubMed:11087660,
CC ECO:0000269|PubMed:28607488}.
CC -!- INDUCTION: Induced during early Th1 cell differentiation, gradually
CC decreasing at later stages. {ECO:0000269|PubMed:15662016}.
CC -!- PTM: Phosphorylations at Ser-52, Tyr-76, Ser-224 and Ser-508 are
CC regulated by mTORC1 (PubMed:28424242). Phosphorylation at Tyr-525 is
CC essential for its interaction GATA3 (PubMed:15662016). Phosphorylation
CC at Tyr-219, Tyr-265 and Tyr-304 enhances its transcriptional activator
CC activity (PubMed:21690296). Phosphorylation at Thr-302 is required for
CC its interaction with NFATC2 (PubMed:23616576).
CC {ECO:0000269|PubMed:15662016, ECO:0000269|PubMed:21690296,
CC ECO:0000269|PubMed:23616576, ECO:0000269|PubMed:28424242}.
CC -!- PTM: Ubiquitinated at Lys-313, leading to its degradation by the
CC proteasome. Ubiquitination is essential for controlling protein
CC stability, binding to the T-box-binding element of the IFN-gamma
CC promoter, and for interaction with NFATC2 through induction of
CC phosphorylation at Thr-302 (PubMed:23616576). Deubiquitinated by USP10
CC leading to its stabilization (By similarity).
CC {ECO:0000250|UniProtKB:Q9UL17, ECO:0000269|PubMed:23616576}.
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DR EMBL; AF241242; AAF61242.1; -; mRNA.
DR EMBL; AF093099; AAF00056.1; -; mRNA.
DR EMBL; AK156271; BAE33650.1; -; mRNA.
DR EMBL; CH466556; EDL16071.1; -; Genomic_DNA.
DR EMBL; BC137986; AAI37987.1; -; mRNA.
DR EMBL; BC137988; AAI37989.1; -; mRNA.
DR CCDS; CCDS25315.1; -.
DR RefSeq; NP_062380.2; NM_019507.2.
DR PDB; 5T1J; X-ray; 2.95 A; A/B=135-326.
DR PDBsum; 5T1J; -.
DR AlphaFoldDB; Q9JKD8; -.
DR SMR; Q9JKD8; -.
DR BioGRID; 208321; 9.
DR IntAct; Q9JKD8; 9.
DR STRING; 10090.ENSMUSP00000001484; -.
DR iPTMnet; Q9JKD8; -.
DR PhosphoSitePlus; Q9JKD8; -.
DR EPD; Q9JKD8; -.
DR MaxQB; Q9JKD8; -.
DR PaxDb; Q9JKD8; -.
DR PRIDE; Q9JKD8; -.
DR ProteomicsDB; 254670; -.
DR Antibodypedia; 4021; 690 antibodies from 44 providers.
DR DNASU; 57765; -.
DR Ensembl; ENSMUST00000001484; ENSMUSP00000001484; ENSMUSG00000001444.
DR GeneID; 57765; -.
DR KEGG; mmu:57765; -.
DR UCSC; uc007ldr.2; mouse.
DR CTD; 30009; -.
DR MGI; MGI:1888984; Tbx21.
DR VEuPathDB; HostDB:ENSMUSG00000001444; -.
DR eggNOG; KOG3585; Eukaryota.
DR GeneTree; ENSGT00940000160397; -.
DR HOGENOM; CLU_014430_8_2_1; -.
DR InParanoid; Q9JKD8; -.
DR OMA; PGAGWPM; -.
DR OrthoDB; 374561at2759; -.
DR PhylomeDB; Q9JKD8; -.
DR TreeFam; TF106341; -.
DR BioGRID-ORCS; 57765; 4 hits in 110 CRISPR screens.
DR ChiTaRS; Tbx21; mouse.
DR PRO; PR:Q9JKD8; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9JKD8; protein.
DR Bgee; ENSMUSG00000001444; Expressed in ureteric bud trunk and 59 other tissues.
DR Genevisible; Q9JKD8; MM.
DR GO; GO:0043025; C:neuronal cell body; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IMP:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0001708; P:cell fate specification; IBA:GO_Central.
DR GO; GO:0071310; P:cellular response to organic substance; IDA:MGI.
DR GO; GO:0072676; P:lymphocyte migration; IMP:UniProtKB.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; IMP:UniProtKB.
DR GO; GO:2000320; P:negative regulation of T-helper 17 cell differentiation; IDA:UniProtKB.
DR GO; GO:2000329; P:negative regulation of T-helper 17 cell lineage commitment; IMP:UniProtKB.
DR GO; GO:2000552; P:negative regulation of T-helper 2 cell cytokine production; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IGI:MGI.
DR GO; GO:0048304; P:positive regulation of isotype switching to IgG isotypes; IMP:MGI.
DR GO; GO:2000556; P:positive regulation of T-helper 1 cell cytokine production; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0050776; P:regulation of immune response; IMP:MGI.
DR GO; GO:0045580; P:regulation of T cell differentiation; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0009615; P:response to virus; IEA:Ensembl.
DR GO; GO:0030217; P:T cell differentiation; IMP:MGI.
DR GO; GO:0002296; P:T-helper 1 cell lineage commitment; IDA:UniProtKB.
DR CDD; cd00182; TBOX; 1.
DR Gene3D; 2.60.40.820; -; 1.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
DR InterPro; IPR046360; T-box_DNA-bd.
DR InterPro; IPR036960; T-box_sf.
DR InterPro; IPR001699; TF_T-box.
DR InterPro; IPR018186; TF_T-box_CS.
DR PANTHER; PTHR11267; PTHR11267; 1.
DR Pfam; PF00907; T-box; 1.
DR PRINTS; PR00937; TBOX.
DR SMART; SM00425; TBOX; 1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR PROSITE; PS01283; TBOX_1; 1.
DR PROSITE; PS01264; TBOX_2; 1.
DR PROSITE; PS50252; TBOX_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; DNA-binding; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..530
FT /note="T-box transcription factor TBX21"
FT /id="PRO_0000184454"
FT DNA_BIND 140..325
FT /note="T-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00201"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 444..530
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 461..483
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 304
FT /note="Essential for its interaction with RUNX1 and its
FT ability to inhibit RUNX1 transcriptional activity and
FT suppress TH17 lineage development"
FT /evidence="ECO:0000269|PubMed:21151104"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:28424242"
FT MOD_RES 55
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:28424242"
FT MOD_RES 76
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:28424242"
FT MOD_RES 117
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:28424242"
FT MOD_RES 219
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000269|PubMed:21690296"
FT MOD_RES 224
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:28424242"
FT MOD_RES 265
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000269|PubMed:21690296"
FT MOD_RES 302
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:23616576"
FT MOD_RES 304
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000269|PubMed:21690296"
FT MOD_RES 508
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:28424242"
FT MOD_RES 525
FT /note="Phosphotyrosine; by ITK"
FT /evidence="ECO:0000269|PubMed:15662016"
FT CROSSLNK 313
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:23616576"
FT MUTAGEN 52
FT /note="S->A: No loss in its ability to induce IFN-gamma.
FT Significant reduction in its ability to induce IFN-gamma
FT and reduced ability to promote addition of permissive
FT chromatin-remodeling mark H3K4Me2 to the IFNG promoter
FT region; when associated with A-76 and A-224."
FT /evidence="ECO:0000269|PubMed:28424242"
FT MUTAGEN 55
FT /note="T->A: No loss in its ability to induce IFN-gamma."
FT /evidence="ECO:0000269|PubMed:28424242"
FT MUTAGEN 76
FT /note="Y->A: No loss in its ability to induce IFN-gamma.
FT Significant reduction in its ability to induce IFN-gamma
FT and reduced ability to promote addition of permissive
FT chromatin-remodeling mark H3K4Me2 to the IFNG promoter
FT region; when associated with A-52 and A-224."
FT /evidence="ECO:0000269|PubMed:28424242"
FT MUTAGEN 117
FT /note="Y->A: No loss in its ability to induce IFN-gamma."
FT /evidence="ECO:0000269|PubMed:28424242"
FT MUTAGEN 208
FT /note="K->R: No effect on DNA-binding or its nuclear
FT localization."
FT /evidence="ECO:0000269|PubMed:23616576"
FT MUTAGEN 219
FT /note="Y->F: Significant loss of ABL1-mediated
FT phosphorylation and loss of transcriptional activator
FT activity; when associated with F-225 and F-304."
FT /evidence="ECO:0000269|PubMed:21690296"
FT MUTAGEN 224
FT /note="S->A: No loss in its ability to induce IFN-gamma.
FT Significant reduction in its ability to induce IFN-gamma
FT and reduced ability to promote addition of permissive
FT chromatin-remodeling mark H3K4Me2 to the IFNG promoter
FT region; when associated with A-52 and A-76."
FT /evidence="ECO:0000269|PubMed:28424242"
FT MUTAGEN 265
FT /note="Y->F: No loss of interaction with RUNX1."
FT /evidence="ECO:0000269|PubMed:21151104"
FT MUTAGEN 265
FT /note="Y->F: Significant loss of ABL1-mediated
FT phosphorylation and loss of transcriptional activator
FT activity; when associated with F-219 and F-304."
FT /evidence="ECO:0000269|PubMed:21690296"
FT MUTAGEN 302
FT /note="T->A: Loss of phosphorylation and its ability to
FT interact with NFATC2. Loss of its ability to suppress IL-2
FT and Th2 cytokine production. No loss of DNA-binding and no
FT loss its ability to activate IFN-gamma transcription."
FT /evidence="ECO:0000269|PubMed:23616576"
FT MUTAGEN 304
FT /note="Y->F: Loss of interaction with RUNX1 and loss of its
FT ability to inhibit RUNX1 transcriptional activity and
FT suppress TH17 lineage development. Significant loss of
FT ABL1-mediated phosphorylation and loss of transcriptional
FT activator activity; when associated with F-219 and F-225."
FT /evidence="ECO:0000269|PubMed:21151104,
FT ECO:0000269|PubMed:21690296"
FT MUTAGEN 310
FT /note="T->A: No loss of phospshorylation."
FT /evidence="ECO:0000269|PubMed:23616576"
FT MUTAGEN 313
FT /note="K->R: Significant loss of ubiquitination. Loss of
FT phosphorylation at T-302 causing loss of its ability to
FT interact with NFATC2. Loss its ability to activate IFN-
FT gamma transcription due to loss of DNA-binding activity.
FT Loss of its ability to suppress IL-2 and Th2 cytokine
FT production. Increased protein stability. Localization seen
FT in both the nucleus and cytoplasm. No loss of interaction
FT with GATA3 and RELA."
FT /evidence="ECO:0000269|PubMed:23616576"
FT MUTAGEN 321
FT /note="K->R: No effect on DNA-binding or its nuclear
FT localization."
FT /evidence="ECO:0000269|PubMed:23616576"
FT MUTAGEN 437
FT /note="Y->F: No loss of interaction with ITK and GATA3."
FT /evidence="ECO:0000269|PubMed:15662016"
FT MUTAGEN 508
FT /note="S->A: No loss of interaction with RUNX1. No loss in
FT its ability to induce IFN-gamma."
FT /evidence="ECO:0000269|PubMed:21151104,
FT ECO:0000269|PubMed:28424242"
FT MUTAGEN 525
FT /note="Y->F: No loss of interaction with RUNX1. Loss of
FT interaction with ITK and GATA3."
FT /evidence="ECO:0000269|PubMed:15662016,
FT ECO:0000269|PubMed:21151104"
FT CONFLICT 482
FT /note="P -> S (in Ref. 2; AAF00056)"
FT /evidence="ECO:0000305"
FT STRAND 138..142
FT /evidence="ECO:0007829|PDB:5T1J"
FT HELIX 143..151
FT /evidence="ECO:0007829|PDB:5T1J"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:5T1J"
FT STRAND 170..173
FT /evidence="ECO:0007829|PDB:5T1J"
FT STRAND 180..193
FT /evidence="ECO:0007829|PDB:5T1J"
FT STRAND 195..199
FT /evidence="ECO:0007829|PDB:5T1J"
FT STRAND 202..207
FT /evidence="ECO:0007829|PDB:5T1J"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:5T1J"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:5T1J"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:5T1J"
FT HELIX 228..233
FT /evidence="ECO:0007829|PDB:5T1J"
FT STRAND 242..245
FT /evidence="ECO:0007829|PDB:5T1J"
FT STRAND 250..253
FT /evidence="ECO:0007829|PDB:5T1J"
FT STRAND 264..273
FT /evidence="ECO:0007829|PDB:5T1J"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:5T1J"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:5T1J"
FT HELIX 294..296
FT /evidence="ECO:0007829|PDB:5T1J"
FT STRAND 298..303
FT /evidence="ECO:0007829|PDB:5T1J"
FT HELIX 307..316
FT /evidence="ECO:0007829|PDB:5T1J"
FT HELIX 321..323
FT /evidence="ECO:0007829|PDB:5T1J"
SQ SEQUENCE 530 AA; 57852 MW; 07E4E9023A227FE8 CRC64;
MGIVEPGCGD MLTGTEPMPS DEGRGPGADQ QHRFFYPEPG AQDPTDRRAG SSLGTPYSGG
ALVPAAPGRF LGSFAYPPRA QVAGFPGPGE FFPPPAGAEG YPPVDGYPAP DPRAGLYPGP
REDYALPAGL EVSGKLRVAL SNHLLWSKFN QHQTEMIITK QGRRMFPFLS FTVAGLEPTS
HYRMFVDVVL VDQHHWRYQS GKWVQCGKAE GSMPGNRLYV HPDSPNTGAH WMRQEVSFGK
LKLTNNKGAS NNVTQMIVLQ SLHKYQPRLH IVEVNDGEPE AACSASNTHV FTFQETQFIA
VTAYQNAEIT QLKIDNNPFA KGFRENFESM YASVDTSVPS PPGPNCQLLG GDPFSPLLSN
QYPVPSRFYP DLPGQPKDMI SQPYWLGTPR EHSYEAEFRA VSMKPTLLPS APGPTVPYYR
GQDVLAPGAG WPVAPQYPPK MSPAGWFRPM RTLPMDPGLG SSEEQGSSPS LWPEVTSLQP
EPSDSGLGEG DTKRRRISPY PSSGDSSSPA GAPSPFDKET EGQFYNYFPN
