O15119 (TBX3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
T-box transcription factor TBX3
Short name=T-box protein 3

Gene names

Name:

TBX3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	743 AA.
Sequence status	Complete.
Protein existence	Evidence 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.8
Subunit structure	Interacts with PML (isoform PML-4). Ref.8
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 process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Ligand	DNA-binding
Molecular function	Developmental protein Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	anterior/posterior axis specification, embryo Inferred from mutant phenotype Ref.2. Source: UniProtKB atrioventricular bundle cell differentiation Inferred from electronic annotation. Source: Compara blood vessel development Inferred from electronic annotation. Source: Compara branching involved in mammary gland duct morphogenesis Inferred from electronic annotation. Source: Compara cardiac muscle cell fate commitment Inferred from electronic annotation. Source: Compara cellular senescence Inferred from direct assay Ref.8. 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 heart looping Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara limbic system development Inferred from electronic annotation. Source: Compara 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: Compara 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: Compara 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: Compara negative regulation of transcription, DNA-dependent 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: Compara palate development Inferred from electronic annotation. Source: Compara 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: Compara positive regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara regulation of transcription from RNA polymerase II promoter Traceable author statement Ref.2. Source: UniProtKB sinoatrial node cell development Inferred from electronic annotation. Source: Compara skeletal system development Inferred from mutant phenotype Ref.2. Source: UniProtKB specification of organ position Inferred from electronic annotation. Source: Compara stem cell maintenance Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW ventricular septum morphogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	nucleus Inferred from direct assay PubMed 11689487. Source: UniProtKB
Molecular_function	RNA polymerase II activating 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: Compara
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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 743

743

T-box transcription factor TBX3

PRO_0000184428

Regions

DNA binding

107 – 220

114

T-box; first part

DNA binding

241 – 305

65

T-box; second part

Region

544 – 695

152

Transcription repression

Amino acid modifications

Modified residue

371

1

Phosphoserine Ref.7

Modified residue

375

1

Phosphoserine By similarity

Modified residue

432

1

Phosphoserine Ref.6

Modified residue

438

1

Phosphoserine Ref.6

Modified residue

707

1

Phosphoserine Ref.7

Modified residue

738

1

Phosphoserine Ref.7

Modified residue

740

1

Phosphoserine Ref.7

Modified residue

742

1

Phosphoserine Ref.7

Natural variations

Alternative sequence

221 – 240

20

Missing in isoform I.

VSP_006384

Alternative sequence

490 – 615

126

Missing in isoform III.

VSP_006385

Alternative sequence

661 – 677

17

Missing in isoform III.

VSP_006386

Natural variant

143

1

L → P in UMS. Ref.3

VAR_009601

Natural variant

149

1

Y → S in UMS. Ref.3

VAR_009602

Experimental info

Sequence conflict

315

1

K → Q in AAF61207. Ref.4

Sequence conflict

616 – 628

13

SAAAS…HRHPF → LRQPQLRCTAPL Ref.1

Sequence conflict

674

1

V → A in AAD50989. Ref.1

Sequence conflict

692

1

L → P in AAD50989. Ref.1

Secondary structure

1

.

.

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743

Helix Strand Turn

Details...

Beta strand

104 – 107

4

Helix

110 – 119

10

Beta strand

122 – 124

3

Beta strand

137 – 142

6

Beta strand

145 – 166

22

Beta strand

169 – 175

7

Beta strand

191 – 193

3

Helix

194 – 197

4

Beta strand

246 – 255

10

Helix

260 – 265

6

Beta strand

269 – 272

4

Helix

274 – 276

3

Beta strand

278 – 283

6

Helix

287 – 296

10

Helix

298 – 303

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform II [UniParc]. Last modified February 12, 2003. Version 4. Checksum: D5572F9CF871E89F	FASTA	743	79,389
	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
	Isoform I [UniParc]. Checksum: 08A64D15A005F0CF	FASTA	723	77,178
	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 ILNSMHKYQP RFHIVRANDI 250 260 270 280 290 300 LKLPYSTFRT YLFPETEFIA VTAYQNDKIT QLKIDNNPFA KGFRDTGNGR REKRKQLTLQ 310 320 330 340 350 360 SMRVFDERHK KENGTSDESS SEQAAFNCFA QASSPAASTV GTSNLKDLCP SEGESDAEAE 370 380 390 400 410 420 SKEEHGPEAC DAAKISTTTS EEPCRDKGSP AVKAHLFAAE RPRDSGRLDK ASPDSRHSPA 430 440 450 460 470 480 TISSSTRGLG AEERRSPVRE GTAPAKVEEA RALPGKEAFA PLTVQTDAAA AHLAQGPLPG 490 500 510 520 530 540 LGFAPGLAGQ QFFNGHPLFL HPSQFAMGGA FSSMAAAGMG PLLATVSGAS TGVSGLDSTA 550 560 570 580 590 600 MASAAAAQGL SGASAATLPF HLQQHVLASQ GLAMSPFGSL FPYPYTYMAA AAAASSAAAS 610 620 630 640 650 660 SSVHRHPFLN LNTMRPRLRY SPYSIPVPVP DGSSLLTTAL PSMAAAAGPL DGKVAALAAS 670 680 690 700 710 720 PASVAVDSGS ELNSRSSTLS SSSMSLSPKL CAEKEAATSE LQSIQRLVSG LEAKPDRSRS ASP
	Isoform III [UniParc]. Checksum: FCCF7491391BE8DA	FASTA	600	65,604
	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 PLTVQTDAAS AAASSSVHRH PFLNLNTMRP RLRYSPYSIP VPVPDGSSLL TTALAASPAS 550 560 570 580 590 600 VAVDSGSELN SRSSTLSSSS MSLSPKLCAE KEAATSELQS IQRLVSGLEA KPDRSRSASP
	Isoform IV (Sequence not available).		–	–

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"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.
[9]	"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.

Web resources

GeneReviews

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.

IPI

IPI00005110.
IPI00219356.
IPI00298944.

RefSeq

NP_005987.3. NM_005996.3.
NP_057653.3. NM_016569.3.

UniGene

Hs.129895.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1H6F	X-ray	1.70	A/B	101-311	[»]

ProteinModelPortal

O15119.

ModBase

Search...

Protein-protein interaction databases

IntAct

O15119. 1 interaction.

STRING

9606.ENSP00000257566.

PTM databases

PhosphoSite

O15119.

Proteomic databases

PaxDb

O15119.

PRIDE

O15119.

Protocols and materials databases

DNASU

6926.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000257566; ENSP00000257566; ENSG00000135111.
ENST00000349155; ENSP00000257567; ENSG00000135111.

GeneID

6926.

KEGG

hsa:6926.

UCSC

uc001tvt.1. human.
uc001tvu.1. human.

Organism-specific databases

CTD

6926.

GeneCards

GC12M115108.

HGNC

HGNC:11602. TBX3.

HPA

HPA005799.

MIM

181450. phenotype.
601621. gene.

neXtProt

NX_O15119.

Orphanet

3138. Ulnar-mammary syndrome.

PharmGKB

PA36365.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG240293.

HOGENOM

HOG000038046.

HOVERGEN

HBG000412.

InParanoid

O15119.

KO

K10177.

OMA

WQGNYSF.

OrthoDB

EOG4JHCFN.

PhylomeDB

O15119.

Gene expression databases

Bgee

O15119.

CleanEx

HS_TBX3.

Genevestigator

O15119.

GermOnline

ENSG00000135111. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.820. 1 hit.

InterPro

IPR008967. p53-like_TF_DNA-bd.
IPR022582. TBX.
IPR001699. TF_T-box.
IPR018186. TF_T-box_CS.
[Graphical view]

PANTHER

PTHR11267. PTHR11267. 1 hit.

Pfam

PF00907. T-box. 1 hit.
PF12598. TBX. 1 hit.
[Graphical view]

PRINTS

PR00937. TBOX.

SMART

SM00425. TBOX. 1 hit.
[Graphical view]

SUPFAM

SSF49417. P53_like_DNA_bnd. 1 hit.

PROSITE

PS01283. TBOX_1. 1 hit.
PS01264. TBOX_2. 1 hit.
PS50252. TBOX_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

TBX3. human.

EvolutionaryTrace

O15119.

GenomeRNAi

6926.

NextBio

27099.

SOURCE

Search...

Entry information

Entry name

TBX3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 143 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.