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 24-JAN-2024, entry version 157. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 10090-ENSMUSP00000001484; -. DR ProteomicsDB; 254670; -. DR Antibodypedia; 4021; 733 antibodies from 44 providers. DR DNASU; 57765; -. DR Ensembl; ENSMUST00000001484.3; ENSMUSP00000001484.3; ENSMUSG00000001444.3. DR GeneID; 57765; -. DR KEGG; mmu:57765; -. DR UCSC; uc007ldr.2; mouse. DR AGR; MGI:1888984; -. 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; HWRYQNG; -. DR OrthoDB; 5323209at2759; -. DR PhylomeDB; Q9JKD8; -. DR TreeFam; TF106341; -. DR BioGRID-ORCS; 57765; 5 hits in 115 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 60 other cell types or tissues. 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:0045892; P:negative regulation of DNA-templated transcription; 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:0045893; P:positive regulation of DNA-templated transcription; IDA: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: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; cd20203; T-box_TBX21; 1. DR Gene3D; 2.60.40.820; Transcription factor, T-box; 1. DR InterPro; IPR008967; p53-like_TF_DNA-bd_sf. 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; T-BOX PROTEIN-RELATED; 1. DR PANTHER; PTHR11267:SF125; T-BOX TRANSCRIPTION FACTOR TBX21; 1. DR Pfam; PF00907; T-box; 1. DR PRINTS; PR00937; TBOX. DR SMART; SM00425; TBOX; 1. DR SUPFAM; SSF49417; p53-like transcription factors; 1. DR PROSITE; PS01283; TBOX_1; 1. DR PROSITE; PS01264; TBOX_2; 1. DR PROSITE; PS50252; TBOX_3; 1. DR Genevisible; Q9JKD8; MM. 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 FT IFN-gamma transcription due to loss of DNA-binding FT activity. Loss of its ability to suppress IL-2 and Th2 FT cytokine production. Increased protein stability. FT Localization seen in both the nucleus and cytoplasm. No FT loss of interaction 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 //