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Protein

T-box transcription factor TBX21

Gene

TBX21

Organism
Homo sapiens (Human)
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 (PubMed:10761931). 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 (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).By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei305Essential for its interaction with RUNX1 and its ability to inhibit RUNX1 transcriptional activity and suppress TH17 lineage developmentBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi141 – 326T-boxPROSITE-ProRule annotationAdd BLAST186

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

SIGNORiQ9UL17.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000073861.2.
HGNCiHGNC:11599. 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

Involvement in diseasei

Asthma, with nasal polyps and aspirin intolerance (ANPAI)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA condition consisting of asthma, aspirin sensitivity and nasal polyposis. Nasal polyposis is due to chronic inflammation of the paranasal sinus mucosa, leading to protrusion of edematous polyps into the nasal cavities.
See also OMIM:208550

Keywords - Diseasei

Asthma

Organism-specific databases

DisGeNETi30009.
MalaCardsiTBX21.
MIMi208550. phenotype.
OpenTargetsiENSG00000073861.
PharmGKBiPA36362.

Polymorphism and mutation databases

BioMutaiTBX21.
DMDMi12230772.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001844531 – 535T-box transcription factor TBX21Add BLAST535

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei53PhosphoserineBy similarity1
Modified residuei77PhosphotyrosineBy similarity1
Modified residuei118PhosphotyrosineBy similarity1
Modified residuei220Phosphotyrosine; by ABL1By similarity1
Modified residuei225PhosphoserineBy similarity1
Modified residuei266Phosphotyrosine; by ABL1By similarity1
Modified residuei303PhosphothreonineBy similarity1
Modified residuei305Phosphotyrosine; by ABL1By similarity1
Cross-linki314Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei513PhosphoserineBy similarity1
Modified residuei530Phosphotyrosine; by ITKBy similarity1

Post-translational modificationi

Phosphorylations at Ser-53, Tyr-77, Ser-225 and Ser-513 are regulated by mTORC1. Phosphorylation at Tyr-530 is essential for its interaction GATA3. Phosphorylation at Tyr-220, Tyr-266 and Tyr-305 enhances its transcriptional activator activity. Phosphorylation at Thr-303 is required for its interaction with NFATC2.By similarity
Ubiquitinated at Lys-314, 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-303 (By similarity). Deubiquitinated by USP10 leading to its stabilization (PubMed:24845384).By similarity1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9UL17.
PaxDbiQ9UL17.
PeptideAtlasiQ9UL17.
PRIDEiQ9UL17.

PTM databases

iPTMnetiQ9UL17.
PhosphoSitePlusiQ9UL17.

Expressioni

Tissue specificityi

T-cell specific.1 Publication

Gene expression databases

BgeeiENSG00000073861.
CleanExiHS_TBX21.
GenevisibleiQ9UL17. HS.

Organism-specific databases

HPAiCAB009524.
CAB030043.

Interactioni

Subunit structurei

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).By similarity3 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi119027. 9 interactors.
DIPiDIP-61303N.
IntActiQ9UL17. 5 interactors.
STRINGi9606.ENSP00000177694.

Structurei

3D structure databases

ProteinModelPortaliQ9UL17.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Phylogenomic databases

eggNOGiKOG3585. Eukaryota.
ENOG410XSTS. LUCA.
GeneTreeiENSGT00900000140847.
HOGENOMiHOG000218633.
HOVERGENiHBG000578.
InParanoidiQ9UL17.
KOiK10166.
OMAiPQPYWLG.
OrthoDBiEOG091G0PQQ.
PhylomeDBiQ9UL17.
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.

Q9UL17-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGIVEPGCGD MLTGTEPMPG SDEGRAPGAD PQHRYFYPEP GAQDADERRG
60 70 80 90 100
GGSLGSPYPG GALVPAPPSR FLGAYAYPPR PQAAGFPGAG ESFPPPADAE
110 120 130 140 150
GYQPGEGYAA PDPRAGLYPG PREDYALPAG LEVSGKLRVA LNNHLLWSKF
160 170 180 190 200
NQHQTEMIIT KQGRRMFPFL SFTVAGLEPT SHYRMFVDVV LVDQHHWRYQ
210 220 230 240 250
SGKWVQCGKA EGSMPGNRLY VHPDSPNTGA HWMRQEVSFG KLKLTNNKGA
260 270 280 290 300
SNNVTQMIVL QSLHKYQPRL HIVEVNDGEP EAACNASNTH IFTFQETQFI
310 320 330 340 350
AVTAYQNAEI TQLKIDNNPF AKGFRENFES MYTSVDTSIP SPPGPNCQFL
360 370 380 390 400
GGDHYSPLLP NQYPVPSRFY PDLPGQAKDV VPQAYWLGAP RDHSYEAEFR
410 420 430 440 450
AVSMKPAFLP SAPGPTMSYY RGQEVLAPGA GWPVAPQYPP KMGPASWFRP
460 470 480 490 500
MRTLPMEPGP GGSEGRGPED QGPPLVWTEI APIRPESSDS GLGEGDSKRR
510 520 530
RVSPYPSSGD SSSPAGAPSP FDKEAEGQFY NYFPN
Length:535
Mass (Da):58,328
Last modified:May 1, 2000 - v1
Checksum:i51F351335598CEF2
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02025233H → Q1 PublicationCorresponds to variant dbSNP:rs2240017Ensembl.1
Natural variantiVAR_029275339I → V. Corresponds to variant dbSNP:rs12721471Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF093098 mRNA. Translation: AAF00055.1.
AF241243 mRNA. Translation: AAF61243.1.
BC039739 mRNA. Translation: AAH39739.1.
CCDSiCCDS11514.1.
RefSeqiNP_037483.1. NM_013351.1.
UniGeneiHs.272409.

Genome annotation databases

EnsembliENST00000177694; ENSP00000177694; ENSG00000073861.
GeneIDi30009.
KEGGihsa:30009.
UCSCiuc002ilv.1. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTBX21_HUMAN
AccessioniPrimary (citable) accession number: Q9UL17
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: May 1, 2000
Last modified: November 22, 2017
This is version 147 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot