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Protein

T-box transcription factor TBX5

Gene

TBX5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 (PubMed:25725155, PubMed:25963046, PubMed:29174768, PubMed:26917986, PubMed:27035640, PubMed:8988164). Binds to the core DNA motif of NPPA promoter (PubMed:26926761).7 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi58 – 238T-boxPROSITE-ProRule annotation1 PublicationAdd BLAST181

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • DNA binding transcription factor activity Source: UniProtKB
  • RNA polymerase II proximal promoter sequence-specific DNA binding Source: UniProtKB
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • sequence-specific DNA binding Source: UniProtKB
  • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: Ensembl
  • transcription factor binding Source: BHF-UCL

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 by RNA polymerase II Source: UniProtKB
  • transcription initiation from RNA polymerase II promoter Source: Reactome
  • ventricular septum development Source: BHF-UCL

Keywordsi

Molecular functionDevelopmental protein, DNA-binding
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-2032785 YAP1- and WWTR1 (TAZ)-stimulated gene expression
R-HSA-5578768 Physiological factors
SIGNORiQ99593

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

EuPathDBiHostDB:ENSG00000089225.19
HGNCiHGNC:11604 TBX5
MIMi601620 gene
neXtProtiNX_Q99593

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

Cytoplasm, 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 dbSNP:rs104894383EnsemblClinVar.1
Natural variantiVAR_01538254I → T in HOS. 1 PublicationCorresponds to variant dbSNP:rs104894384EnsemblClinVar.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 dbSNP:rs104894381EnsemblClinVar.1
Natural variantiVAR_007456237R → Q in HOS; extensive upper limb malformations; affects transcriptional regulation of MYH6. 3 PublicationsCorresponds to variant dbSNP:rs104894378EnsemblClinVar.1
Natural variantiVAR_009702237R → W in HOS; extensive upper limb malformations; strongly reduced affinity for DNA. 2 PublicationsCorresponds to variant dbSNP:rs104894382EnsemblClinVar.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.4 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi234K → R: Does not affect acetylation of the protein. 1 Publication1
Mutagenesisi325K → R: Does not affect transcription factor activity. 1 Publication1
Mutagenesisi327K → R: Does not affect transcription factor activity. 1 Publication1
Mutagenesisi339K → R: Abolishes acetylation of the protein, leading to impaired transcription factor activity. Impaired subcellular location. 1 Publication1
Mutagenesisi340K → R: Does not affect transcription factor activity. 1 Publication1

Keywords - Diseasei

Atrial fibrillation, Cardiomyopathy, Disease mutation

Organism-specific databases

DisGeNETi6910
GeneReviewsiTBX5
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

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei339N6-acetyllysine1 Publication1

Post-translational modificationi

Acetylation at Lys-339 by KAT2A and KAT2B promotes nuclear retention.1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ99593
PaxDbiQ99593
PeptideAtlasiQ99593
PRIDEiQ99593
ProteomicsDBi78347
78348 [Q99593-2]

PTM databases

iPTMnetiQ99593
PhosphoSitePlusiQ99593

Expressioni

Gene expression databases

BgeeiENSG00000089225
CleanExiHS_TBX5
GenevisibleiQ99593 HS

Organism-specific databases

HPAiHPA008786
HPA064683

Interactioni

Subunit structurei

Monomer (PubMed:20450920). Homodimer (via the T-box); binds DNA as homodimer (PubMed:26926761). Interacts (via the T-box) with NKX2-5 (via the homeobox); this complex binds DNA (PubMed:26926761). Interacts with GATA4 (PubMed:24000169). Interacts with KAT2A and KAT2B (PubMed:29174768).4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi112773, 7 interactors
CORUMiQ99593
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

ProteinModelPortaliQ99593
SMRiQ99593
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99593

Family & Domainsi

Domaini

The T-Box domain binds to double-stranded DNA (PubMed:26926761).1 Publication

Phylogenomic databases

eggNOGiKOG3585 Eukaryota
ENOG410XSTS LUCA
GeneTreeiENSGT00760000118897
HOGENOMiHOG000286001
HOVERGENiHBG007310
InParanoidiQ99593
KOiK10179
OMAiRKDEECS
OrthoDBiEOG091G0I8R
PhylomeDBiQ99593
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

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 dbSNP:rs104894383EnsemblClinVar.1
Natural variantiVAR_01538254I → T in HOS. 1 PublicationCorresponds to variant dbSNP:rs104894384EnsemblClinVar.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 dbSNP:rs104894381EnsemblClinVar.1
Natural variantiVAR_076673132P → S Probable disease-associated mutation found in a patient with atrial fibrillation; 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 dbSNP:rs374906778Ensembl.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-associated mutation found in a patient with atrial fibrillation; 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 dbSNP:rs104894378EnsemblClinVar.1
Natural variantiVAR_009702237R → W in HOS; extensive upper limb malformations; strongly reduced affinity for DNA. 2 PublicationsCorresponds to variant dbSNP:rs104894382EnsemblClinVar.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

Similar proteinsi

Entry informationi

Entry nameiTBX5_HUMAN
AccessioniPrimary (citable) accession number: Q99593
Secondary accession number(s): A6ND77
, O15301, Q96TB0, Q9Y4I2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: December 1, 2000
Last modified: July 18, 2018
This is version 182 of the entry and version 2 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

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

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