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Protein

T-box transcription factor TBX3

Gene

TBX3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcriptional repressor involved in developmental processes. Probably plays a role in limb pattern formation. Acts as a negative regulator of PML function in cellular senescence.2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi107 – 220114T-box; first partPROSITE-ProRule annotationAdd
BLAST
DNA bindingi241 – 30565T-box; second partPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • anterior/posterior axis specification, embryo Source: UniProtKB
  • atrioventricular bundle cell differentiation Source: Ensembl
  • blood vessel development Source: Ensembl
  • branching involved in mammary gland duct morphogenesis Source: Ensembl
  • cardiac muscle cell fate commitment Source: Ensembl
  • cell aging Source: UniProtKB
  • cellular senescence Source: UniProtKB
  • embryonic digit morphogenesis Source: UniProtKB
  • embryonic forelimb morphogenesis Source: UniProtKB
  • female genitalia development Source: UniProtKB
  • follicle-stimulating hormone secretion Source: UniProtKB
  • forelimb morphogenesis Source: MGI
  • heart looping Source: Ensembl
  • in utero embryonic development Source: Ensembl
  • limbic system development Source: Ensembl
  • luteinizing hormone secretion Source: UniProtKB
  • male genitalia development Source: UniProtKB
  • mammary gland development Source: UniProtKB
  • mammary placode formation Source: Ensembl
  • mesoderm morphogenesis Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of epithelial cell differentiation Source: Ensembl
  • negative regulation of myoblast differentiation Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • organ morphogenesis Source: MGI
  • outflow tract morphogenesis Source: Ensembl
  • palate development Source: Ensembl
  • positive regulation of cell cycle Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of stem cell proliferation Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: Ensembl
  • regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • sinoatrial node cell development Source: Ensembl
  • skeletal system development Source: UniProtKB
  • specification of organ position Source: Ensembl
  • stem cell maintenance Source: Ensembl
  • ventricular septum morphogenesis Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
T-box transcription factor TBX3
Short name:
T-box protein 3
Gene namesi
Name:TBX3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:11602. TBX3.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Ulnar-mammary syndrome (UMS)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionCharacterized by ulnar ray defects, obesity, hypogenitalism, delayed puberty, hypoplasia of nipples and apocrine glands.

See also OMIM:181450
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti143 – 1431L → P in UMS. 1 Publication
VAR_009601
Natural varianti149 – 1491Y → S in UMS. 1 Publication
VAR_009602

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi181450. phenotype.
Orphaneti3138. Ulnar-mammary syndrome.
PharmGKBiPA36365.

Polymorphism and mutation databases

BioMutaiTBX3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 743743T-box transcription factor TBX3PRO_0000184428Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei371 – 3711Phosphoserine1 Publication
Modified residuei432 – 4321Phosphoserine1 Publication
Modified residuei438 – 4381Phosphoserine2 Publications
Modified residuei707 – 7071Phosphoserine1 Publication
Modified residuei738 – 7381Phosphoserine1 Publication
Modified residuei740 – 7401Phosphoserine1 Publication
Modified residuei742 – 7421Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO15119.
PaxDbiO15119.
PRIDEiO15119.

PTM databases

PhosphoSiteiO15119.

Expressioni

Tissue specificityi

Widely expressed.

Gene expression databases

BgeeiO15119.
CleanExiHS_TBX3.
ExpressionAtlasiO15119. baseline and differential.
GenevisibleiO15119. HS.

Organism-specific databases

HPAiHPA005799.

Interactioni

Subunit structurei

Interacts with PML (isoform PML-4).1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
AESQ081173EBI-3452216,EBI-717810
CA8P352193EBI-3452216,EBI-718700

Protein-protein interaction databases

BioGridi112788. 13 interactions.
IntActiO15119. 4 interactions.
MINTiMINT-7970169.
STRINGi9606.ENSP00000257566.

Structurei

Secondary structure

1
743
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi104 – 1074Combined sources
Helixi110 – 11910Combined sources
Beta strandi122 – 1243Combined sources
Beta strandi137 – 1426Combined sources
Beta strandi145 – 16622Combined sources
Beta strandi169 – 1757Combined sources
Beta strandi191 – 1933Combined sources
Helixi194 – 1974Combined sources
Beta strandi246 – 25510Combined sources
Helixi260 – 2656Combined sources
Beta strandi269 – 2724Combined sources
Helixi274 – 2763Combined sources
Beta strandi278 – 2836Combined sources
Helixi287 – 29610Combined sources
Helixi298 – 3036Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1H6FX-ray1.70A/B101-311[»]
ProteinModelPortaliO15119.
SMRiO15119. Positions 100-305.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO15119.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni544 – 695152Transcription repressionAdd
BLAST

Sequence similaritiesi

Contains 1 T-box DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG240293.
GeneTreeiENSGT00760000118897.
HOGENOMiHOG000038046.
HOVERGENiHBG000412.
InParanoidiO15119.
KOiK10177.
OMAiPSQFAMG.
OrthoDBiEOG7W9RV1.
PhylomeDBiO15119.
TreeFamiTF106341.

Family and domain databases

Gene3Di2.60.40.820. 1 hit.
InterProiIPR008967. p53-like_TF_DNA-bd.
IPR022582. TBX.
IPR001699. TF_T-box.
IPR018186. TF_T-box_CS.
[Graphical view]
PANTHERiPTHR11267. PTHR11267. 1 hit.
PfamiPF00907. T-box. 1 hit.
PF12598. TBX. 1 hit.
[Graphical view]
PRINTSiPR00937. TBOX.
SMARTiSM00425. TBOX. 1 hit.
[Graphical view]
SUPFAMiSSF49417. SSF49417. 1 hit.
PROSITEiPS01283. TBOX_1. 1 hit.
PS01264. TBOX_2. 1 hit.
PS50252. TBOX_3. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform II (identifier: O15119-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSLSMRDPVI PGTSMAYHPF LPHRAPDFAM SAVLGHQPPF FPALTLPPNG
60 70 80 90 100
AAALSLPGAL AKPIMDQLVG AAETGIPFSS LGPQAHLRPL KTMEPEEEVE
110 120 130 140 150
DDPKVHLEAK ELWDQFHKRG TEMVITKSGR RMFPPFKVRC SGLDKKAKYI
160 170 180 190 200
LLMDIIAADD CRYKFHNSRW MVAGKADPEM PKRMYIHPDS PATGEQWMSK
210 220 230 240 250
VVTFHKLKLT NNISDKHGFT LAFPSDHATW QGNYSFGTQT ILNSMHKYQP
260 270 280 290 300
RFHIVRANDI LKLPYSTFRT YLFPETEFIA VTAYQNDKIT QLKIDNNPFA
310 320 330 340 350
KGFRDTGNGR REKRKQLTLQ SMRVFDERHK KENGTSDESS SEQAAFNCFA
360 370 380 390 400
QASSPAASTV GTSNLKDLCP SEGESDAEAE SKEEHGPEAC DAAKISTTTS
410 420 430 440 450
EEPCRDKGSP AVKAHLFAAE RPRDSGRLDK ASPDSRHSPA TISSSTRGLG
460 470 480 490 500
AEERRSPVRE GTAPAKVEEA RALPGKEAFA PLTVQTDAAA AHLAQGPLPG
510 520 530 540 550
LGFAPGLAGQ QFFNGHPLFL HPSQFAMGGA FSSMAAAGMG PLLATVSGAS
560 570 580 590 600
TGVSGLDSTA MASAAAAQGL SGASAATLPF HLQQHVLASQ GLAMSPFGSL
610 620 630 640 650
FPYPYTYMAA AAAASSAAAS SSVHRHPFLN LNTMRPRLRY SPYSIPVPVP
660 670 680 690 700
DGSSLLTTAL PSMAAAAGPL DGKVAALAAS PASVAVDSGS ELNSRSSTLS
710 720 730 740
SSSMSLSPKL CAEKEAATSE LQSIQRLVSG LEAKPDRSRS ASP
Note: Contains an interrupted T-box domain.
Length:743
Mass (Da):79,389
Last modified:February 12, 2003 - v4
Checksum:iD5572F9CF871E89F
GO
Isoform I (identifier: O15119-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     221-240: Missing.

Show »
Length:723
Mass (Da):77,178
Checksum:i08A64D15A005F0CF
GO
Isoform III (identifier: O15119-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     490-615: Missing.
     661-677: Missing.

Note: Contains an interrupted T-box domain.
Show »
Length:600
Mass (Da):65,604
Checksum:iFCCF7491391BE8DA
GO
Isoform IV (identifier: O15119-4)

Sequence is not available
Note: May be produced by joining exon 1 to exon 7 thereby eliminating the T-box.
Length:
Mass (Da):

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti315 – 3151K → Q in AAF61207 (Ref. 4) Curated
Sequence conflicti616 – 62813SAAAS…HRHPF → LRQPQLRCTAPL (PubMed:10468588).CuratedAdd
BLAST
Sequence conflicti674 – 6741V → A in AAD50989 (PubMed:10468588).Curated
Sequence conflicti692 – 6921L → P in AAD50989 (PubMed:10468588).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti143 – 1431L → P in UMS. 1 Publication
VAR_009601
Natural varianti149 – 1491Y → S in UMS. 1 Publication
VAR_009602

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei221 – 24020Missing in isoform I. 2 PublicationsVSP_006384Add
BLAST
Alternative sequencei490 – 615126Missing in isoform III. 1 PublicationVSP_006385Add
BLAST
Alternative sequencei661 – 67717Missing in isoform III. 1 PublicationVSP_006386Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF170708 mRNA. Translation: AAD50989.2.
AF002228 mRNA. Translation: AAC12947.1.
AF140240 mRNA. Translation: AAF61816.1.
AF216750 mRNA. Translation: AAF61207.1.
BC025258 mRNA. Translation: AAH25258.1.
CCDSiCCDS9175.1. [O15119-2]
CCDS9176.1. [O15119-1]
RefSeqiNP_005987.3. NM_005996.3. [O15119-2]
NP_057653.3. NM_016569.3. [O15119-1]
UniGeneiHs.744016.

Genome annotation databases

EnsembliENST00000257566; ENSP00000257566; ENSG00000135111. [O15119-1]
ENST00000349155; ENSP00000257567; ENSG00000135111. [O15119-2]
GeneIDi6926.
KEGGihsa:6926.
UCSCiuc001tvt.1. human. [O15119-1]
uc001tvu.1. human. [O15119-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF170708 mRNA. Translation: AAD50989.2.
AF002228 mRNA. Translation: AAC12947.1.
AF140240 mRNA. Translation: AAF61816.1.
AF216750 mRNA. Translation: AAF61207.1.
BC025258 mRNA. Translation: AAH25258.1.
CCDSiCCDS9175.1. [O15119-2]
CCDS9176.1. [O15119-1]
RefSeqiNP_005987.3. NM_005996.3. [O15119-2]
NP_057653.3. NM_016569.3. [O15119-1]
UniGeneiHs.744016.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1H6FX-ray1.70A/B101-311[»]
ProteinModelPortaliO15119.
SMRiO15119. Positions 100-305.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112788. 13 interactions.
IntActiO15119. 4 interactions.
MINTiMINT-7970169.
STRINGi9606.ENSP00000257566.

PTM databases

PhosphoSiteiO15119.

Polymorphism and mutation databases

BioMutaiTBX3.

Proteomic databases

MaxQBiO15119.
PaxDbiO15119.
PRIDEiO15119.

Protocols and materials databases

DNASUi6926.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000257566; ENSP00000257566; ENSG00000135111. [O15119-1]
ENST00000349155; ENSP00000257567; ENSG00000135111. [O15119-2]
GeneIDi6926.
KEGGihsa:6926.
UCSCiuc001tvt.1. human. [O15119-1]
uc001tvu.1. human. [O15119-2]

Organism-specific databases

CTDi6926.
GeneCardsiGC12M115108.
HGNCiHGNC:11602. TBX3.
HPAiHPA005799.
MIMi181450. phenotype.
601621. gene.
neXtProtiNX_O15119.
Orphaneti3138. Ulnar-mammary syndrome.
PharmGKBiPA36365.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG240293.
GeneTreeiENSGT00760000118897.
HOGENOMiHOG000038046.
HOVERGENiHBG000412.
InParanoidiO15119.
KOiK10177.
OMAiPSQFAMG.
OrthoDBiEOG7W9RV1.
PhylomeDBiO15119.
TreeFamiTF106341.

Miscellaneous databases

ChiTaRSiTBX3. human.
EvolutionaryTraceiO15119.
GeneWikiiTBX3.
GenomeRNAii6926.
NextBioi27099.
PROiO15119.
SOURCEiSearch...

Gene expression databases

BgeeiO15119.
CleanExiHS_TBX3.
ExpressionAtlasiO15119. baseline and differential.
GenevisibleiO15119. HS.

Family and domain databases

Gene3Di2.60.40.820. 1 hit.
InterProiIPR008967. p53-like_TF_DNA-bd.
IPR022582. TBX.
IPR001699. TF_T-box.
IPR018186. TF_T-box_CS.
[Graphical view]
PANTHERiPTHR11267. PTHR11267. 1 hit.
PfamiPF00907. T-box. 1 hit.
PF12598. TBX. 1 hit.
[Graphical view]
PRINTSiPR00937. TBOX.
SMARTiSM00425. TBOX. 1 hit.
[Graphical view]
SUPFAMiSSF49417. SSF49417. 1 hit.
PROSITEiPS01283. TBOX_1. 1 hit.
PS01264. TBOX_2. 1 hit.
PS50252. TBOX_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Transcription repression by Xenopus ET and its human ortholog TBX3, a gene involved in ulnar-mammary syndrome."
    He M.-L., Wen L., Campbell C.E., Wu J.Y., Rao Y.
    Proc. Natl. Acad. Sci. U.S.A. 96:10212-10217(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM I), FUNCTION.
    Tissue: Mammary carcinoma.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-488 (ISOFORM I).
    Tissue: Kidney.
  3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 592-743, ALTERNATIVE SPLICING, VARIANTS UMS PRO-143 AND SER-149.
  4. "A novel gene expressed in human adrenal gland."
    Song H., Gao G., Peng Y., Ren S., Chen Z., Han Z.
    Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM III).
    Tissue: Adrenal gland.
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM II).
    Tissue: Brain.
  6. "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
    Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
    J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-432 AND SER-438, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-371; SER-707; SER-738; SER-740 AND SER-742, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  8. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. "Physical and functional interaction between PML and TBX2 in the establishment of cellular senescence."
    Martin N., Benhamed M., Nacerddine K., Demarque M.D., van Lohuizen M., Dejean A., Bischof O.
    EMBO J. 31:95-109(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH PML.
  10. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-438, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  11. "Structure of the DNA-bound T-box domain of human TBX3, a transcription factor responsible for ulnar-mammary syndrome."
    Coll M., Seidman J.G., Muller C.W.
    Structure 10:343-356(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 101-311.

Entry informationi

Entry nameiTBX3_HUMAN
AccessioniPrimary (citable) accession number: O15119
Secondary accession number(s): Q8TB20, Q9UKF8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: February 12, 2003
Last modified: June 24, 2015
This is version 161 of the entry and version 4 of the sequence. [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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: 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
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.