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Protein

T-box transcription factor TBX5

Gene

TBX5

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

Functioni

DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation.5 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi58 – 238T-boxPROSITE-ProRule annotationAdd BLAST181

GO - Molecular functioni

GO - Biological processi

  • atrial septum morphogenesis Source: Ensembl
  • atrioventricular valve morphogenesis Source: Ensembl
  • bundle of His development Source: Ensembl
  • cardiac left ventricle formation Source: BHF-UCL
  • cardiac muscle cell differentiation Source: Ensembl
  • cell-cell signaling Source: UniProtKB
  • cell migration involved in coronary vasculogenesis Source: DFLAT
  • embryonic forelimb morphogenesis Source: UniProtKB
  • embryonic limb morphogenesis Source: UniProtKB
  • endocardial cushion development Source: Ensembl
  • forelimb morphogenesis Source: MGI
  • heart development Source: UniProtKB
  • lung development Source: Ensembl
  • morphogenesis of an epithelium Source: Ensembl
  • negative regulation of cardiac muscle cell proliferation Source: UniProtKB
  • negative regulation of cell migration Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of epithelial to mesenchymal transition Source: DFLAT
  • pattern specification process Source: Ensembl
  • pericardium development Source: UniProtKB
  • positive regulation of cardiac muscle cell proliferation Source: Ensembl
  • positive regulation of cardioblast differentiation Source: UniProtKB
  • positive regulation of secondary heart field cardioblast proliferation Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • regulation of execution phase of apoptosis Source: UniProtKB
  • transcription initiation from RNA polymerase II promoter Source: Reactome
  • ventricular septum development Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000089225-MONOMER.
ReactomeiR-HSA-2032785. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
R-HSA-5578768. Physiological factors.

Names & Taxonomyi

Protein namesi
Recommended name:
T-box transcription factor TBX5
Short name:
T-box protein 5
Gene namesi
Name:TBX5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:11604. TBX5.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Holt-Oram syndrome (HOS)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionDevelopmental disorder affecting the heart and upper limbs. It is characterized by thumb anomaly and atrial septal defects.
See also OMIM:142900
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01538149Q → K in HOS. 1 PublicationCorresponds to variant rs104894383dbSNPEnsembl.1
Natural variantiVAR_01538254I → T in HOS. 1 PublicationCorresponds to variant rs104894384dbSNPEnsembl.1
Natural variantiVAR_00970180G → R in HOS; significant cardiac malformations but only minor skeletal abnormalities; reduced protein stability and strongly reduced affinity for DNA. 2 PublicationsCorresponds to variant rs104894381dbSNPEnsembl.1
Natural variantiVAR_007456237R → Q in HOS; extensive upper limb malformations; affects transcriptional regulation of MYH6. 3 PublicationsCorresponds to variant rs104894378dbSNPEnsembl.1
Natural variantiVAR_009702237R → W in HOS; extensive upper limb malformations; strongly reduced affinity for DNA. 2 PublicationsCorresponds to variant rs104894382dbSNPEnsembl.1

Defects in TBX5 are associated with susceptibility to heart disorders including dilated cardiomyopathy (DCM) and atrial fibrillation (AF). DCM is characterized by ventricular and impaired systolic function, resulting in heart failure and arrhythmia. Patient are at risk of premature death. AF is a common sustained cardiac rhythm disturbance. AF is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure.

Keywords - Diseasei

Atrial fibrillation, Cardiomyopathy, Disease mutation

Organism-specific databases

DisGeNETi6910.
MalaCardsiTBX5.
MIMi142900. phenotype.
OpenTargetsiENSG00000089225.
Orphaneti392. Holt-Oram syndrome.
PharmGKBiPA36367.

Chemistry databases

ChEMBLiCHEMBL1687681.

Polymorphism and mutation databases

BioMutaiTBX5.
DMDMi12644474.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001844351 – 518T-box transcription factor TBX5Add BLAST518

Proteomic databases

PaxDbiQ99593.
PeptideAtlasiQ99593.
PRIDEiQ99593.

PTM databases

iPTMnetiQ99593.
PhosphoSitePlusiQ99593.

Expressioni

Gene expression databases

BgeeiENSG00000089225.
CleanExiHS_TBX5.
GenevisibleiQ99593. HS.

Organism-specific databases

HPAiHPA008786.
HPA064683.

Interactioni

Subunit structurei

Monomer. Interacts with GATA4.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Gata4Q083692EBI-297043,EBI-297008From a different organism.
NKX2-5P529526EBI-304423,EBI-936601
YAP1P469374EBI-297043,EBI-1044059

GO - Molecular functioni

  • transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi112773. 7 interactors.
IntActiQ99593. 9 interactors.
STRINGi9606.ENSP00000309913.

Structurei

Secondary structure

1518
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi43 – 48Combined sources6
Beta strandi55 – 58Combined sources4
Helixi61 – 70Combined sources10
Beta strandi73 – 75Combined sources3
Beta strandi77 – 79Combined sources3
Beta strandi88 – 93Combined sources6
Beta strandi96 – 117Combined sources22
Beta strandi120 – 126Combined sources7
Beta strandi142 – 144Combined sources3
Helixi145 – 150Combined sources6
Beta strandi153 – 155Combined sources3
Beta strandi159 – 161Combined sources3
Beta strandi177 – 187Combined sources11
Beta strandi194 – 197Combined sources4
Beta strandi201 – 204Combined sources4
Helixi207 – 209Combined sources3
Beta strandi211 – 216Combined sources6
Helixi220 – 229Combined sources10
Helixi231 – 236Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2X6UX-ray1.90A51-251[»]
2X6VX-ray2.20A/B51-251[»]
4S0HX-ray2.82A/E53-238[»]
5BQDX-ray2.58A/B1-239[»]
ProteinModelPortaliQ99593.
SMRiQ99593.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99593.

Family & Domainsi

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG3585. Eukaryota.
ENOG410XSTS. LUCA.
GeneTreeiENSGT00760000118897.
HOGENOMiHOG000286001.
HOVERGENiHBG007310.
InParanoidiQ99593.
KOiK10179.
OMAiDSKDLPC.
OrthoDBiEOG091G0I8R.
PhylomeDBiQ99593.
TreeFamiTF106341.

Family and domain databases

CDDicd00182. TBOX. 1 hit.
Gene3Di2.60.40.820. 1 hit.
InterProiIPR008967. p53-like_TF_DNA-bd.
IPR001699. TF_T-box.
IPR018186. TF_T-box_CS.
[Graphical view]
PANTHERiPTHR11267. PTHR11267. 1 hit.
PfamiPF00907. T-box. 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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q99593-1) [UniParc]FASTAAdd to basket
Also known as: Long

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
MADADEGFGL AHTPLEPDAK DLPCDSKPES ALGAPSKSPS SPQAAFTQQG
60 70 80 90 100
MEGIKVFLHE RELWLKFHEV GTEMIITKAG RRMFPSYKVK VTGLNPKTKY
110 120 130 140 150
ILLMDIVPAD DHRYKFADNK WSVTGKAEPA MPGRLYVHPD SPATGAHWMR
160 170 180 190 200
QLVSFQKLKL TNNHLDPFGH IILNSMHKYQ PRLHIVKADE NNGFGSKNTA
210 220 230 240 250
FCTHVFPETA FIAVTSYQNH KITQLKIENN PFAKGFRGSD DMELHRMSRM
260 270 280 290 300
QSKEYPVVPR STVRQKVASN HSPFSSESRA LSTSSNLGSQ YQCENGVSGP
310 320 330 340 350
SQDLLPPPNP YPLPQEHSQI YHCTKRKEEE CSTTDHPYKK PYMETSPSEE
360 370 380 390 400
DSFYRSSYPQ QQGLGASYRT ESAQRQACMY ASSAPPSEPV PSLEDISCNT
410 420 430 440 450
WPSMPSYSSC TVTTVQPMDR LPYQHFSAHF TSGPLVPRLA GMANHGSPQL
460 470 480 490 500
GEGMFQHQTS VAHQPVVRQC GPQTGLQSPG TLQPPEFLYS HGVPRTLSPH
510
QYHSVHGVGM VPEWSDNS
Length:518
Mass (Da):57,711
Last modified:December 1, 2000 - v2
Checksum:i70118AD84FF5C00F
GO
Isoform 2 (identifier: Q99593-2) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     328-349: EEECSTTDHPYKKPYMETSPSE → GECDHPWSICFLSYLFLSLGWG
     350-518: Missing.

Show »
Length:349
Mass (Da):39,196
Checksum:i50CE556CD97ACD76
GO
Isoform 3 (identifier: Q99593-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-50: Missing.

Show »
Length:468
Mass (Da):52,659
Checksum:iF0434B124BB31A5A
GO

Sequence cautioni

The sequence BAB55448 differs from that shown. Reason: Frameshift at position 360.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti7 – 49GFGLA…AFTQQ → ALAGAHLWSLTQKTCLRFEP RARSGPPASPPGRPRSRLHP A in CAA70592 (PubMed:8988164).CuratedAdd BLAST43
Sequence conflicti71Missing in CAA70592 (PubMed:8988164).Curated1
Sequence conflicti94L → I in CAA70592 (PubMed:8988164).Curated1
Sequence conflicti122S → C in CAA70592 (PubMed:8988164).Curated1
Sequence conflicti132P → A in CAA70592 (PubMed:8988164).Curated1
Sequence conflicti418 – 460MDRLP…QHQTS → WTGYPTSTSPLTSPRGPWSL GWLAWQPWLPTAGRGNVPST RPP in CAA70592 (PubMed:8988164).CuratedAdd BLAST43
Sequence conflicti468 – 470RQC → SSV in CAA70592 (PubMed:8988164).Curated3
Sequence conflicti494 – 518PRTLS…WSDNS → QGLYPLISTTLCTELAWCRV ERQ in CAA70592 (PubMed:8988164).CuratedAdd BLAST25

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01538149Q → K in HOS. 1 PublicationCorresponds to variant rs104894383dbSNPEnsembl.1
Natural variantiVAR_01538254I → T in HOS. 1 PublicationCorresponds to variant rs104894384dbSNPEnsembl.1
Natural variantiVAR_00970180G → R in HOS; significant cardiac malformations but only minor skeletal abnormalities; reduced protein stability and strongly reduced affinity for DNA. 2 PublicationsCorresponds to variant rs104894381dbSNPEnsembl.1
Natural variantiVAR_076673132P → S Probable disease mutation in AF; reduces transcriptional activity; affects transcriptional regulation of NKX2-5. 1 Publication1
Natural variantiVAR_074599143A → T Probable disease-associated mutation found in a patient with sporadic dilated cardiomyopathy; associated with disease susceptibility; associated with significantly decreased transcriptional activity. 1 PublicationCorresponds to variant rs374906778dbSNPEnsembl.1
Natural variantiVAR_074600154S → A Probable disease-associated mutation found in patients with familial dilated cardiomyopathy; associated with disease susceptibility; associated with significantly decreased transcriptional activity. 1 Publication1
Natural variantiVAR_076642170H → D Probable disease mutation in AF; reduces transcriptional activity; affects transcriptional regulation of NKX2-5 or GATA4. 1 Publication1
Natural variantiVAR_007456237R → Q in HOS; extensive upper limb malformations; affects transcriptional regulation of MYH6. 3 PublicationsCorresponds to variant rs104894378dbSNPEnsembl.1
Natural variantiVAR_009702237R → W in HOS; extensive upper limb malformations; strongly reduced affinity for DNA. 2 PublicationsCorresponds to variant rs104894382dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0468451 – 50Missing in isoform 3. 1 PublicationAdd BLAST50
Alternative sequenceiVSP_006387328 – 349EEECS…TSPSE → GECDHPWSICFLSYLFLSLG WG in isoform 2. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_006388350 – 518Missing in isoform 2. 1 PublicationAdd BLAST169

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y09445 mRNA. Translation: CAA70592.1.
U80987 mRNA. Translation: AAC51644.1.
U89353 mRNA. Translation: AAC04619.1.
AF221714 mRNA. Translation: AAF34659.1.
AB051068 mRNA. Translation: BAB55448.1. Frameshift.
AC009260 Genomic DNA. No translation available.
AC069240 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW98066.1.
BC027942 mRNA. Translation: AAH27942.1.
CCDSiCCDS9173.1. [Q99593-1]
CCDS9174.1. [Q99593-3]
RefSeqiNP_000183.2. NM_000192.3. [Q99593-1]
NP_542448.1. NM_080717.2. [Q99593-3]
NP_852259.1. NM_181486.2. [Q99593-1]
UniGeneiHs.381715.

Genome annotation databases

EnsembliENST00000310346; ENSP00000309913; ENSG00000089225. [Q99593-1]
ENST00000349716; ENSP00000337723; ENSG00000089225. [Q99593-3]
ENST00000405440; ENSP00000384152; ENSG00000089225. [Q99593-1]
ENST00000526441; ENSP00000433292; ENSG00000089225. [Q99593-2]
GeneIDi6910.
KEGGihsa:6910.
UCSCiuc001tvo.5. human. [Q99593-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y09445 mRNA. Translation: CAA70592.1.
U80987 mRNA. Translation: AAC51644.1.
U89353 mRNA. Translation: AAC04619.1.
AF221714 mRNA. Translation: AAF34659.1.
AB051068 mRNA. Translation: BAB55448.1. Frameshift.
AC009260 Genomic DNA. No translation available.
AC069240 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW98066.1.
BC027942 mRNA. Translation: AAH27942.1.
CCDSiCCDS9173.1. [Q99593-1]
CCDS9174.1. [Q99593-3]
RefSeqiNP_000183.2. NM_000192.3. [Q99593-1]
NP_542448.1. NM_080717.2. [Q99593-3]
NP_852259.1. NM_181486.2. [Q99593-1]
UniGeneiHs.381715.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2X6UX-ray1.90A51-251[»]
2X6VX-ray2.20A/B51-251[»]
4S0HX-ray2.82A/E53-238[»]
5BQDX-ray2.58A/B1-239[»]
ProteinModelPortaliQ99593.
SMRiQ99593.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112773. 7 interactors.
IntActiQ99593. 9 interactors.
STRINGi9606.ENSP00000309913.

Chemistry databases

ChEMBLiCHEMBL1687681.

PTM databases

iPTMnetiQ99593.
PhosphoSitePlusiQ99593.

Polymorphism and mutation databases

BioMutaiTBX5.
DMDMi12644474.

Proteomic databases

PaxDbiQ99593.
PeptideAtlasiQ99593.
PRIDEiQ99593.

Protocols and materials databases

DNASUi6910.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000310346; ENSP00000309913; ENSG00000089225. [Q99593-1]
ENST00000349716; ENSP00000337723; ENSG00000089225. [Q99593-3]
ENST00000405440; ENSP00000384152; ENSG00000089225. [Q99593-1]
ENST00000526441; ENSP00000433292; ENSG00000089225. [Q99593-2]
GeneIDi6910.
KEGGihsa:6910.
UCSCiuc001tvo.5. human. [Q99593-1]

Organism-specific databases

CTDi6910.
DisGeNETi6910.
GeneCardsiTBX5.
GeneReviewsiTBX5.
HGNCiHGNC:11604. TBX5.
HPAiHPA008786.
HPA064683.
MalaCardsiTBX5.
MIMi142900. phenotype.
601620. gene.
neXtProtiNX_Q99593.
OpenTargetsiENSG00000089225.
Orphaneti392. Holt-Oram syndrome.
PharmGKBiPA36367.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3585. Eukaryota.
ENOG410XSTS. LUCA.
GeneTreeiENSGT00760000118897.
HOGENOMiHOG000286001.
HOVERGENiHBG007310.
InParanoidiQ99593.
KOiK10179.
OMAiDSKDLPC.
OrthoDBiEOG091G0I8R.
PhylomeDBiQ99593.
TreeFamiTF106341.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000089225-MONOMER.
ReactomeiR-HSA-2032785. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
R-HSA-5578768. Physiological factors.

Miscellaneous databases

EvolutionaryTraceiQ99593.
GeneWikiiTBX5_(gene).
GenomeRNAii6910.
PROiQ99593.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000089225.
CleanExiHS_TBX5.
GenevisibleiQ99593. HS.

Family and domain databases

CDDicd00182. TBOX. 1 hit.
Gene3Di2.60.40.820. 1 hit.
InterProiIPR008967. p53-like_TF_DNA-bd.
IPR001699. TF_T-box.
IPR018186. TF_T-box_CS.
[Graphical view]
PANTHERiPTHR11267. PTHR11267. 1 hit.
PfamiPF00907. T-box. 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...

Entry informationi

Entry nameiTBX5_HUMAN
AccessioniPrimary (citable) accession number: Q99593
Secondary accession number(s): A6ND77
, O15301, Q96TB0, Q9Y4I2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: December 1, 2000
Last modified: November 30, 2016
This is version 170 of the entry and version 2 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

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 one 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.