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Protein

T-box transcription factor TBX21

Gene

Tbx21

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Activates transcription of a set of genes important for Th1 cell function, including those encoding IFN-gamma and the chemokine receptor CXCR3. 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 (PubMed:10761931, PubMed:17923685, PubMed:21095589). 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 (PubMed:21151104). 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 (PubMed:15662016, PubMed:21690296, PubMed:23616576). 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 (PubMed:28623086). 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 (PubMed:27430722).11 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei304Essential for its interaction with RUNX1 and its ability to inhibit RUNX1 transcriptional activity and suppress TH17 lineage development1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi140 – 325T-boxPROSITE-ProRule annotationAdd BLAST186

GO - Molecular functioni

GO - Biological processi

  • cellular response to organic substance Source: MGI
  • lymphocyte migration Source: UniProtKB
  • negative regulation of interleukin-2 production Source: UniProtKB
  • negative regulation of T-helper 17 cell differentiation Source: UniProtKB
  • negative regulation of T-helper 17 cell lineage commitment Source: UniProtKB
  • negative regulation of T-helper 2 cell cytokine production Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of isotype switching to IgG isotypes Source: MGI
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • regulation of immune response Source: MGI
  • regulation of T cell differentiation Source: UniProtKB
  • response to virus Source: Ensembl
  • T cell differentiation Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionActivator, DNA-binding, Repressor
Biological processTranscription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
T-box transcription factor TBX21
Short name:
T-box protein 21
Alternative name(s):
T-cell-specific T-box transcription factor T-bet
Transcription factor TBLYM
Gene namesi
Name:Tbx21
Synonyms:Tbet, Tblym
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1888984. Tbx21.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi52S → A: No loss in its ability to induce IFN-gamma. Significant reduction in its ability to induce IFN-gamma and reduced ability to promote addition of permissive chromatin-remodeling mark H3K4Me2 to the IFNG promoter region; when associated with A-76 and A-224. 1 Publication1
Mutagenesisi55T → A: No loss in its ability to induce IFN-gamma. 1 Publication1
Mutagenesisi76Y → A: No loss in its ability to induce IFN-gamma. Significant reduction in its ability to induce IFN-gamma and reduced ability to promote addition of permissive chromatin-remodeling mark H3K4Me2 to the IFNG promoter region; when associated with A-52 and A-224. 1 Publication1
Mutagenesisi117Y → A: No loss in its ability to induce IFN-gamma. 1 Publication1
Mutagenesisi208K → R: No effect on DNA-binding or its nuclear localization. 1 Publication1
Mutagenesisi219Y → F: Significant loss of ABL1-mediated phosphorylation and loss of transcriptional activator activity; when associated with F-225 and F-304. 1 Publication1
Mutagenesisi224S → A: No loss in its ability to induce IFN-gamma. Significant reduction in its ability to induce IFN-gamma and reduced ability to promote addition of permissive chromatin-remodeling mark H3K4Me2 to the IFNG promoter region; when associated with A-52 and A-76. 1 Publication1
Mutagenesisi265Y → F: No loss of interaction with RUNX1. 1 Publication1
Mutagenesisi265Y → F: Significant loss of ABL1-mediated phosphorylation and loss of transcriptional activator activity; when associated with F-219 and F-304. 1 Publication1
Mutagenesisi302T → A: Loss of phosphorylation and its ability to interact with NFATC2. Loss of its ability to suppress IL-2 and Th2 cytokine production. No loss of DNA-binding and no loss its ability to activate IFN-gamma transcription. 1 Publication1
Mutagenesisi304Y → F: Loss of interaction with RUNX1 and loss of its ability to inhibit RUNX1 transcriptional activity and suppress TH17 lineage development. Significant loss of ABL1-mediated phosphorylation and loss of transcriptional activator activity; when associated with F-219 and F-225. 2 Publications1
Mutagenesisi310T → A: No loss of phospshorylation. 1 Publication1
Mutagenesisi313K → R: Significant loss of ubiquitination. Loss of phosphorylation at T-302 causing loss of its ability to interact with NFATC2. Loss its ability to activate IFN-gamma transcription due to loss of DNA-binding activity. Loss of its ability to suppress IL-2 and Th2 cytokine production. Increased protein stability. Localization seen in both the nucleus and cytoplasm. No loss of interaction with GATA3 and RELA. 1 Publication1
Mutagenesisi321K → R: No effect on DNA-binding or its nuclear localization. 1 Publication1
Mutagenesisi437Y → F: No loss of interaction with ITK and GATA3. 1 Publication1
Mutagenesisi508S → A: No loss of interaction with RUNX1. No loss in its ability to induce IFN-gamma. 2 Publications1
Mutagenesisi525Y → F: No loss of interaction with RUNX1. Loss of interaction with ITK and GATA3. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001844541 – 530T-box transcription factor TBX21Add BLAST530

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei52Phosphoserine1 Publication1
Modified residuei55Phosphothreonine1 Publication1
Modified residuei76Phosphotyrosine1 Publication1
Modified residuei117Phosphotyrosine1 Publication1
Modified residuei219Phosphotyrosine; by ABL11 Publication1
Modified residuei224Phosphoserine1 Publication1
Modified residuei265Phosphotyrosine; by ABL11 Publication1
Modified residuei302Phosphothreonine1 Publication1
Modified residuei304Phosphotyrosine; by ABL11 Publication1
Cross-linki313Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei508Phosphoserine1 Publication1
Modified residuei525Phosphotyrosine; by ITK1 Publication1

Post-translational modificationi

Phosphorylations at Ser-52, Tyr-76, Ser-224 and Ser-508 are regulated by mTORC1 (PubMed:28424242). Phosphorylation at Tyr-525 is essential for its interaction GATA3 (PubMed:15662016). Phosphorylation at Tyr-219, Tyr-265 and Tyr-304 enhances its transcriptional activator activity (PubMed:21690296). Phosphorylation at Thr-302 is required for its interaction with NFATC2 (PubMed:23616576).4 Publications
Ubiquitinated at Lys-313, leading to its degradation by the proteasome. Ubiquitination is essential for controlling protein stability, binding to the T-box-binding element of the IFN-gamma promoter, and for interaction with NFATC2 through induction of phosphorylation at Thr-302 (PubMed:23616576). Deubiquitinated by USP10 leading to its stabilization (By similarity).By similarity1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9JKD8.
MaxQBiQ9JKD8.
PaxDbiQ9JKD8.
PRIDEiQ9JKD8.

PTM databases

iPTMnetiQ9JKD8.
PhosphoSitePlusiQ9JKD8.

Expressioni

Tissue specificityi

T-cell specific (PubMed:10761931, PubMed:11087660). Expressed in regulatory T (TReg) cells (PubMed:28607488).3 Publications

Inductioni

Induced during early Th1 cell differentiation, gradually decreasing at later stages.1 Publication

Gene expression databases

BgeeiENSMUSG00000001444.
CleanExiMM_TBX21.
ExpressionAtlasiQ9JKD8. baseline and differential.
GenevisibleiQ9JKD8. MM.

Interactioni

Subunit structurei

Interacts with RUNX1 and RUNX3 (PubMed:21151104). Interacts with ITK (PubMed:15662016). The phosphorylated form (at Tyr-525) interacts with GATA3 (PubMed:15662016, PubMed:21690296, PubMed:23616576). Interacts with ABL1 (PubMed:21690296). Interacts with RELA (PubMed:23616576). The phosphorylated form (at Thr-302) interacts with NFATC2 (PubMed:23616576). Interacts with KDM6B (PubMed:21095589). Interacts with SMARCA4 in a KDM6B-dependent manner (PubMed:21095589). Interacts with CCTN1 and CDK9 (PubMed:27292648). Interacts with USP10 (By similarity).By similarity6 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi208321. 9 interactors.
IntActiQ9JKD8. 3 interactors.
STRINGi10090.ENSMUSP00000001484.

Structurei

Secondary structure

1530
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi138 – 142Combined sources5
Helixi143 – 151Combined sources9
Beta strandi155 – 157Combined sources3
Beta strandi170 – 173Combined sources4
Beta strandi180 – 193Combined sources14
Beta strandi195 – 199Combined sources5
Beta strandi202 – 207Combined sources6
Beta strandi212 – 214Combined sources3
Beta strandi218 – 220Combined sources3
Beta strandi225 – 227Combined sources3
Helixi228 – 233Combined sources6
Beta strandi242 – 245Combined sources4
Beta strandi250 – 253Combined sources4
Beta strandi264 – 273Combined sources10
Beta strandi279 – 281Combined sources3
Beta strandi290 – 292Combined sources3
Helixi294 – 296Combined sources3
Beta strandi298 – 303Combined sources6
Helixi307 – 316Combined sources10
Helixi321 – 323Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5T1JX-ray2.95A/B135-326[»]
ProteinModelPortaliQ9JKD8.
SMRiQ9JKD8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Phylogenomic databases

eggNOGiKOG3585. Eukaryota.
ENOG410XSTS. LUCA.
GeneTreeiENSGT00900000140847.
HOGENOMiHOG000218633.
HOVERGENiHBG000578.
InParanoidiQ9JKD8.
KOiK10166.
OMAiPQPYWLG.
OrthoDBiEOG091G0PQQ.
PhylomeDBiQ9JKD8.
TreeFamiTF106341.

Family and domain databases

CDDicd00182. TBOX. 1 hit.
Gene3Di2.60.40.820. 1 hit.
InterProiView protein in InterPro
IPR008967. p53-like_TF_DNA-bd.
IPR036960. T-box_sf.
IPR001699. TF_T-box.
IPR018186. TF_T-box_CS.
PANTHERiPTHR11267. PTHR11267. 1 hit.
PfamiView protein in Pfam
PF00907. T-box. 1 hit.
PRINTSiPR00937. TBOX.
SMARTiView protein in SMART
SM00425. TBOX. 1 hit.
SUPFAMiSSF49417. SSF49417. 1 hit.
PROSITEiView protein in PROSITE
PS01283. TBOX_1. 1 hit.
PS01264. TBOX_2. 1 hit.
PS50252. TBOX_3. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9JKD8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGIVEPGCGD MLTGTEPMPS DEGRGPGADQ QHRFFYPEPG AQDPTDRRAG
60 70 80 90 100
SSLGTPYSGG ALVPAAPGRF LGSFAYPPRA QVAGFPGPGE FFPPPAGAEG
110 120 130 140 150
YPPVDGYPAP DPRAGLYPGP REDYALPAGL EVSGKLRVAL SNHLLWSKFN
160 170 180 190 200
QHQTEMIITK QGRRMFPFLS FTVAGLEPTS HYRMFVDVVL VDQHHWRYQS
210 220 230 240 250
GKWVQCGKAE GSMPGNRLYV HPDSPNTGAH WMRQEVSFGK LKLTNNKGAS
260 270 280 290 300
NNVTQMIVLQ SLHKYQPRLH IVEVNDGEPE AACSASNTHV FTFQETQFIA
310 320 330 340 350
VTAYQNAEIT QLKIDNNPFA KGFRENFESM YASVDTSVPS PPGPNCQLLG
360 370 380 390 400
GDPFSPLLSN QYPVPSRFYP DLPGQPKDMI SQPYWLGTPR EHSYEAEFRA
410 420 430 440 450
VSMKPTLLPS APGPTVPYYR GQDVLAPGAG WPVAPQYPPK MSPAGWFRPM
460 470 480 490 500
RTLPMDPGLG SSEEQGSSPS LWPEVTSLQP EPSDSGLGEG DTKRRRISPY
510 520 530
PSSGDSSSPA GAPSPFDKET EGQFYNYFPN
Length:530
Mass (Da):57,852
Last modified:October 1, 2000 - v1
Checksum:i07E4E9023A227FE8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti482P → S in AAF00056 (PubMed:11087660).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF241242 mRNA. Translation: AAF61242.1.
AF093099 mRNA. Translation: AAF00056.1.
AK156271 mRNA. Translation: BAE33650.1.
CH466556 Genomic DNA. Translation: EDL16071.1.
BC137986 mRNA. Translation: AAI37987.1.
BC137988 mRNA. Translation: AAI37989.1.
CCDSiCCDS25315.1.
RefSeqiNP_062380.2. NM_019507.2.
UniGeneiMm.94519.

Genome annotation databases

EnsembliENSMUST00000001484; ENSMUSP00000001484; ENSMUSG00000001444.
GeneIDi57765.
KEGGimmu:57765.
UCSCiuc007ldr.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiTBX21_MOUSE
AccessioniPrimary (citable) accession number: Q9JKD8
Secondary accession number(s): Q3U150, Q9R0A6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: October 1, 2000
Last modified: November 22, 2017
This is version 123 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references