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O15119 (TBX3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
T-box transcription factor TBX3

Short name=T-box protein 3
Gene names
Name:TBX3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length743 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.9

Subunit structure

Interacts with PML (isoform PML-4) Ref.9

Subcellular location

Nucleus Potential.

Tissue specificity

Widely expressed.

Involvement in disease

Ulnar-mammary syndrome (UMS) [MIM:181450]: Characterized by ulnar ray defects, obesity, hypogenitalism, delayed puberty, hypoplasia of nipples and apocrine glands.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3

Sequence similarities

Contains 1 T-box DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   LigandDNA-binding
   Molecular functionDevelopmental protein
Repressor
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processanterior/posterior axis specification, embryo

Inferred from mutant phenotype Ref.2. Source: UniProtKB

atrioventricular bundle cell differentiation

Inferred from electronic annotation. Source: Ensembl

blood vessel development

Inferred from electronic annotation. Source: Ensembl

branching involved in mammary gland duct morphogenesis

Inferred from electronic annotation. Source: Ensembl

cardiac muscle cell fate commitment

Inferred from electronic annotation. Source: Ensembl

cell aging

Inferred from direct assay PubMed 11689487PubMed 11748239. Source: UniProtKB

cellular senescence

Inferred from direct assay Ref.9. Source: UniProtKB

embryonic digit morphogenesis

Inferred from mutant phenotype PubMed 12116211Ref.2. Source: UniProtKB

embryonic forelimb morphogenesis

Inferred from mutant phenotype PubMed 12116211. Source: UniProtKB

female genitalia development

Inferred from mutant phenotype PubMed 12116211. Source: UniProtKB

follicle-stimulating hormone secretion

Inferred from mutant phenotype PubMed 12116211. Source: UniProtKB

forelimb morphogenesis

Inferred from direct assay Ref.2. Source: MGI

heart looping

Inferred from electronic annotation. Source: Ensembl

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

limbic system development

Inferred from electronic annotation. Source: Ensembl

luteinizing hormone secretion

Inferred from mutant phenotype PubMed 12116211. Source: UniProtKB

male genitalia development

Inferred from mutant phenotype PubMed 12116211. Source: UniProtKB

mammary gland development

Inferred from mutant phenotype PubMed 12116211. Source: UniProtKB

mammary placode formation

Inferred from electronic annotation. Source: Ensembl

mesoderm morphogenesis

Inferred from mutant phenotype Ref.2. Source: UniProtKB

negative regulation of apoptotic process

Inferred from direct assay PubMed 12032820. Source: UniProtKB

negative regulation of epithelial cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of myoblast differentiation

Inferred from direct assay PubMed 12032820. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription, DNA-templated

Inferred from direct assay Ref.1PubMed 11689487. Source: UniProtKB

organ morphogenesis

Inferred from direct assay Ref.2. Source: MGI

outflow tract morphogenesis

Inferred from electronic annotation. Source: Ensembl

palate development

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell cycle

Inferred from direct assay PubMed 12032820. Source: UniProtKB

positive regulation of cell proliferation

Inferred from direct assay PubMed 11689487PubMed 11748239PubMed 12032820. Source: UniProtKB

positive regulation of stem cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: Ensembl

regulation of transcription from RNA polymerase II promoter

Traceable author statement Ref.2. Source: UniProtKB

sinoatrial node cell development

Inferred from electronic annotation. Source: Ensembl

skeletal system development

Inferred from mutant phenotype Ref.2. Source: UniProtKB

specification of organ position

Inferred from electronic annotation. Source: Ensembl

stem cell maintenance

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

ventricular septum morphogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentnucleus

Inferred from direct assay PubMed 11689487. Source: UniProtKB

   Molecular_functionRNA polymerase II activating transcription factor binding

Inferred from sequence or structural similarity. Source: BHF-UCL

RNA polymerase II transcription factor binding

Inferred from sequence or structural similarity. Source: BHF-UCL

sequence-specific DNA binding

Inferred from direct assay PubMed 11689487. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform II (identifier: O15119-1)

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.
Note: Contains an interrupted T-box domain.
Isoform I (identifier: O15119-2)

The sequence of this isoform differs from the canonical sequence as follows:
     221-240: Missing.
Isoform III (identifier: O15119-3)

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.
Isoform IV (identifier: O15119-4)

The sequence of this isoform is not available.
Note: May be produced by joining exon 1 to exon 7 thereby eliminating the T-box.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 743743T-box transcription factor TBX3
PRO_0000184428

Regions

DNA binding107 – 220114T-box; first part
DNA binding241 – 30565T-box; second part
Region544 – 695152Transcription repression

Amino acid modifications

Modified residue3711Phosphoserine Ref.7
Modified residue4321Phosphoserine Ref.6
Modified residue4381Phosphoserine Ref.6
Modified residue7071Phosphoserine Ref.7
Modified residue7381Phosphoserine Ref.7
Modified residue7401Phosphoserine Ref.7
Modified residue7421Phosphoserine Ref.7

Natural variations

Alternative sequence221 – 24020Missing in isoform I.
VSP_006384
Alternative sequence490 – 615126Missing in isoform III.
VSP_006385
Alternative sequence661 – 67717Missing in isoform III.
VSP_006386
Natural variant1431L → P in UMS. Ref.3
VAR_009601
Natural variant1491Y → S in UMS. Ref.3
VAR_009602

Experimental info

Sequence conflict3151K → Q in AAF61207. Ref.4
Sequence conflict616 – 62813SAAAS…HRHPF → LRQPQLRCTAPL Ref.1
Sequence conflict6741V → A in AAD50989. Ref.1
Sequence conflict6921L → P in AAD50989. Ref.1

Secondary structure

.............................. 743
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform II [UniParc].

Last modified February 12, 2003. Version 4.
Checksum: D5572F9CF871E89F

FASTA74379,389
        10         20         30         40         50         60 
MSLSMRDPVI PGTSMAYHPF LPHRAPDFAM SAVLGHQPPF FPALTLPPNG AAALSLPGAL 

        70         80         90        100        110        120 
AKPIMDQLVG AAETGIPFSS LGPQAHLRPL KTMEPEEEVE DDPKVHLEAK ELWDQFHKRG 

       130        140        150        160        170        180 
TEMVITKSGR RMFPPFKVRC SGLDKKAKYI LLMDIIAADD CRYKFHNSRW MVAGKADPEM 

       190        200        210        220        230        240 
PKRMYIHPDS PATGEQWMSK VVTFHKLKLT NNISDKHGFT LAFPSDHATW QGNYSFGTQT 

       250        260        270        280        290        300 
ILNSMHKYQP RFHIVRANDI LKLPYSTFRT YLFPETEFIA VTAYQNDKIT QLKIDNNPFA 

       310        320        330        340        350        360 
KGFRDTGNGR REKRKQLTLQ SMRVFDERHK KENGTSDESS SEQAAFNCFA QASSPAASTV 

       370        380        390        400        410        420 
GTSNLKDLCP SEGESDAEAE SKEEHGPEAC DAAKISTTTS EEPCRDKGSP AVKAHLFAAE 

       430        440        450        460        470        480 
RPRDSGRLDK ASPDSRHSPA TISSSTRGLG AEERRSPVRE GTAPAKVEEA RALPGKEAFA 

       490        500        510        520        530        540 
PLTVQTDAAA AHLAQGPLPG LGFAPGLAGQ QFFNGHPLFL HPSQFAMGGA FSSMAAAGMG 

       550        560        570        580        590        600 
PLLATVSGAS TGVSGLDSTA MASAAAAQGL SGASAATLPF HLQQHVLASQ GLAMSPFGSL 

       610        620        630        640        650        660 
FPYPYTYMAA AAAASSAAAS SSVHRHPFLN LNTMRPRLRY SPYSIPVPVP DGSSLLTTAL 

       670        680        690        700        710        720 
PSMAAAAGPL DGKVAALAAS PASVAVDSGS ELNSRSSTLS SSSMSLSPKL CAEKEAATSE 

       730        740 
LQSIQRLVSG LEAKPDRSRS ASP 

« Hide

Isoform I [UniParc].

Checksum: 08A64D15A005F0CF
Show »

FASTA72377,178
Isoform III [UniParc].

Checksum: FCCF7491391BE8DA
Show »

FASTA60065,604
Isoform IV (Sequence not available).

References

« Hide 'large scale' references
[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]"Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome."
Bamshad M., Lin R.C., Law D.J., Watkins W.S., Krakowiak P.A., Moore M.E., Franceschini P., Lala R., Holmes L.B., Gebuhr T.C., Schinzel A., Bruneau B.G., Seidman J.G., Seidman C.E., Jorde L.B.
Nat. Genet. 16:311-315(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-488 (ISOFORM I).
Tissue: Kidney.
[3]"The spectrum of mutations in TBX3: genotype/phenotype relationship in ulnar-mammary syndrome."
Bamshad M., Le T., Watkins W.S., Dixon M.E., Kramer B.E., Roeder A.D., Carey J.C., Root S., Schinzel A., Van Maldergem L., Gardner R.J.M., Lin R.C., Seidman C.E., Seidman J.G., Wallerstein R., Moran E., Sutphen R., Campbell C.E., Jorde L.B.
Am. J. Hum. Genet. 64:1550-1562(1999) [PubMed] [Europe PMC] [Abstract]
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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_005987.3. NM_005996.3.
NP_057653.3. NM_016569.3.
UniGeneHs.744016.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1H6FX-ray1.70A/B101-311[»]
ProteinModelPortalO15119.
SMRO15119. Positions 100-305.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112788. 9 interactions.
IntActO15119. 2 interactions.
MINTMINT-7970169.
STRING9606.ENSP00000257566.

PTM databases

PhosphoSiteO15119.

Proteomic databases

PaxDbO15119.
PRIDEO15119.

Protocols and materials databases

DNASU6926.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000257566; ENSP00000257566; ENSG00000135111. [O15119-1]
ENST00000349155; ENSP00000257567; ENSG00000135111. [O15119-2]
GeneID6926.
KEGGhsa:6926.
UCSCuc001tvt.1. human. [O15119-1]
uc001tvu.1. human. [O15119-2]

Organism-specific databases

CTD6926.
GeneCardsGC12M115108.
HGNCHGNC:11602. TBX3.
HPAHPA005799.
MIM181450. phenotype.
601621. gene.
neXtProtNX_O15119.
Orphanet3138. Ulnar-mammary syndrome.
PharmGKBPA36365.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG240293.
HOGENOMHOG000038046.
HOVERGENHBG000412.
InParanoidO15119.
KOK10177.
OMAPSQFAMG.
OrthoDBEOG7W9RV1.
PhylomeDBO15119.
TreeFamTF106341.

Gene expression databases

BgeeO15119.
CleanExHS_TBX3.
GenevestigatorO15119.

Family and domain databases

Gene3D2.60.40.820. 1 hit.
InterProIPR008967. p53-like_TF_DNA-bd.
IPR022582. TBX.
IPR001699. TF_T-box.
IPR018186. TF_T-box_CS.
[Graphical view]
PANTHERPTHR11267. PTHR11267. 1 hit.
PfamPF00907. T-box. 1 hit.
PF12598. TBX. 1 hit.
[Graphical view]
PRINTSPR00937. TBOX.
SMARTSM00425. TBOX. 1 hit.
[Graphical view]
SUPFAMSSF49417. SSF49417. 1 hit.
PROSITEPS01283. TBOX_1. 1 hit.
PS01264. TBOX_2. 1 hit.
PS50252. TBOX_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTBX3. human.
EvolutionaryTraceO15119.
GeneWikiTBX3.
GenomeRNAi6926.
NextBio27099.
PROO15119.
SOURCESearch...

Entry information

Entry nameTBX3_HUMAN
AccessionPrimary (citable) accession number: O15119
Secondary accession number(s): Q8TB20, Q9UKF8
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: February 12, 2003
Last modified: April 16, 2014
This is version 151 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM