TBX5

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 key	Position(s)	DescriptionActions	Graphical view	Length
DNA bindingⁱ	58 – 238	T-boxPROSITE-ProRule annotation1 PublicationAdd BLAST		181

GO - Molecular functionⁱ

DNA binding
Source: UniProtKB
Inferred from direct assayⁱ
- "A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt-Oram syndrome."
  Murakami M., Nakagawa M., Olson E.N., Nakagawa O.
  Proc. Natl. Acad. Sci. U.S.A. 102:18034-18039(2005) [PubMed] [Europe PMC] [Abstract]
DNA-binding transcription activator activity, RNA polymerase II-specific
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
  Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
  Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
DNA-binding transcription factor activity
Source: UniProtKB
Inferred from direct assayⁱ
- "Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation."
  Hiroi Y., Kudoh S., Monzen K., Ikeda Y., Yazaki Y., Nagai R., Komuro I.
  Nat. Genet. 28:276-280(2001) [PubMed] [Europe PMC] [Abstract]
- "Functional analysis of TBX5 missense mutations associated with Holt-Oram syndrome."
  Fan C., Liu M., Wang Q.
  J. Biol. Chem. 278:8780-8785(2003) [PubMed] [Europe PMC] [Abstract]
- "A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt-Oram syndrome."
  Murakami M., Nakagawa M., Olson E.N., Nakagawa O.
  Proc. Natl. Acad. Sci. U.S.A. 102:18034-18039(2005) [PubMed] [Europe PMC] [Abstract]
DNA-binding transcription factor activity, RNA polymerase II-specific
Source: UniProtKB
Inferred from direct assayⁱ
- Ref.13
  "Acetylation of TBX5 by KAT2B and KAT2A regulates heart and limb development."
  Ghosh T.K., Aparicio-Sanchez J.J., Buxton S., Ketley A., Mohamed T., Rutland C.S., Loughna S., Brook J.D.
  J. Mol. Cell. Cardiol. 114:185-198(2017) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, SUBCELLULAR LOCATION, ACETYLATION AT LYS-339, MUTAGENESIS OF LYS-234; LYS-325; LYS-327; LYS-339 AND LYS-340.
RNA polymerase II activating transcription factor binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
  Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
  Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
RNA polymerase II cis-regulatory region sequence-specific DNA binding
Source: UniProtKB
Inferred from direct assayⁱ
- Ref.15
  "Intermolecular interactions of cardiac transcription factors NKX2.5 and TBX5."
  Pradhan L., Gopal S., Li S., Ashur S., Suryanarayanan S., Kasahara H., Nam H.J.
  Biochemistry 55:1702-1710(2016) [PubMed] [Europe PMC] [Abstract]
  Cited for: X-RAY CRYSTALLOGRAPHY (2.58 ANGSTROMS) OF 1-239 OF HOMODIMER AND DNA, X-RAY CRYSTALLOGRAPHY (2.82 ANGSTROMS) OF 53-238 IN COMPLEX WITH NKX2-5 AND DNA, INTERACTION WITH NKX2-5, DNA-BINDING.
RNA polymerase II transcription regulatory region sequence-specific DNA binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
  Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
  Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
sequence-specific DNA binding
Source: UniProtKB
Inferred from direct assayⁱ
- "Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation."
  Hiroi Y., Kudoh S., Monzen K., Ikeda Y., Yazaki Y., Nagai R., Komuro I.
  Nat. Genet. 28:276-280(2001) [PubMed] [Europe PMC] [Abstract]
- "Functional analysis of TBX5 missense mutations associated with Holt-Oram syndrome."
  Fan C., Liu M., Wang Q.
  J. Biol. Chem. 278:8780-8785(2003) [PubMed] [Europe PMC] [Abstract]
transcription factor binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- "Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation."
  Hiroi Y., Kudoh S., Monzen K., Ikeda Y., Yazaki Y., Nagai R., Komuro I.
  Nat. Genet. 28:276-280(2001) [PubMed] [Europe PMC] [Abstract]

Complete GO annotation on QuickGO ...

GO - Biological processⁱ

Complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Developmental protein, DNA-binding
Biological process	Transcription, Transcription regulation

Enzyme and pathway databases

PathwayCommonsⁱ	Q99593
Reactomeⁱ	R-HSA-2032785, YAP1- and WWTR1 (TAZ)-stimulated gene expression R-HSA-5578768, Physiological factors
SIGNORⁱ	Q99593

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: T-box transcription factor TBX5 Short name: T-box protein 5
Gene namesⁱ	Name:TBX5
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 12

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000089225.19
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:11604, TBX5
MIMⁱ	601620, gene
neXtProtⁱ	NX_Q99593

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.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_015381	49	Q → K in HOS. 1 PublicationCorresponds to variant dbSNP:rs104894383EnsemblClinVar.	1
Natural variantⁱVAR_015382	54	I → T in HOS. 1 PublicationCorresponds to variant dbSNP:rs104894384EnsemblClinVar.	1
Natural variantⁱVAR_009701	80	G → 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_007456	237	R → Q in HOS; extensive upper limb malformations; affects transcriptional regulation of MYH6. 3 PublicationsCorresponds to variant dbSNP:rs104894378EnsemblClinVar.	1
Natural variantⁱVAR_009702	237	R → 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 key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	234	K → R: Does not affect acetylation of the protein. 1 Publication	1
Mutagenesisⁱ	325	K → R: Does not affect transcription factor activity. 1 Publication	1
Mutagenesisⁱ	327	K → R: Does not affect transcription factor activity. 1 Publication	1
Mutagenesisⁱ	339	K → R: Abolishes acetylation of the protein, leading to impaired transcription factor activity. Impaired subcellular location. 1 Publication	1
Mutagenesisⁱ	340	K → R: Does not affect transcription factor activity. 1 Publication	1

Keywords - Diseaseⁱ

Atrial fibrillation, Cardiomyopathy, Disease mutation

Organism-specific databases

DisGeNET More...DisGeNETⁱ	6910
GeneReviewsⁱ	TBX5
MalaCards human disease database More...MalaCardsⁱ	TBX5
MIMⁱ	142900, phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000089225
Orphanetⁱ	392, Holt-Oram syndrome
PharmGKBⁱ	PA36367

Miscellaneous databases

Pharosⁱ	Q99593, Tbio

Pharosⁱ

Q99593, Tbio

Chemistry databases

ChEMBLⁱ	CHEMBL1687681

ChEMBLⁱ

CHEMBL1687681

Polymorphism and mutation databases

BioMutaⁱ	TBX5
DMDMⁱ	12644474

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000184435	1 – 518	T-box transcription factor TBX5Add BLAST		518

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Modified residueⁱ	339	N6-acetyllysine1 Publication		1

Post-translational modificationⁱ

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

Keywords - PTMⁱ

Acetylation

Proteomic databases

jPOSTⁱ	Q99593
MassIVEⁱ	Q99593
PaxDbⁱ	Q99593
PeptideAtlas More...PeptideAtlasⁱ	Q99593
PRIDEⁱ	Q99593
ProteomicsDBⁱ	78347 [Q99593-1] 78348 [Q99593-2] 886

PTM databases

iPTMnetⁱ	Q99593
PhosphoSitePlusⁱ	Q99593

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSG00000089225, Expressed in tendon of biceps brachii and 127 other tissues
Genevisibleⁱ	Q99593, HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	ENSG00000089225, Tissue enhanced (heart muscle, lung, placenta)

HPAⁱ

ENSG00000089225, Tissue enhanced (heart muscle, lung, placenta)

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

Hide details

Q99593

With	#Exp.	IntAct
BAIAP2 - isoform 6 [Q9UQB8-6]	3	EBI-297043,EBI-9092016
YAP1 [P46937]	4	EBI-297043,EBI-1044059
ZMYND10 [O75800]	3	EBI-297043,EBI-747061
Gata4 [Q08369] from Mus musculus.	2	EBI-297043,EBI-297008

Isoform 1 [Q99593-1]

With	#Exp.	IntAct
NKX2-5 [P52952]	6	EBI-304423,EBI-936601

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGRIDⁱ	112773, 9 interactors
CORUMⁱ	Q99593
IntActⁱ	Q99593, 9 interactors
STRINGⁱ	9606.ENSP00000309913

Miscellaneous databases

RNActⁱ	Q99593, protein

RNActⁱ

Q99593, protein

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	43 – 48	Combined sources	6
Beta strandⁱ	55 – 58	Combined sources	4
Helixⁱ	61 – 70	Combined sources	10
Beta strandⁱ	73 – 75	Combined sources	3
Beta strandⁱ	77 – 79	Combined sources	3
Beta strandⁱ	88 – 93	Combined sources	6
Beta strandⁱ	96 – 117	Combined sources	22
Beta strandⁱ	120 – 126	Combined sources	7
Beta strandⁱ	142 – 144	Combined sources	3
Helixⁱ	145 – 150	Combined sources	6
Beta strandⁱ	153 – 155	Combined sources	3
Beta strandⁱ	159 – 161	Combined sources	3
Beta strandⁱ	177 – 187	Combined sources	11
Beta strandⁱ	194 – 197	Combined sources	4
Beta strandⁱ	201 – 204	Combined sources	4
Helixⁱ	207 – 209	Combined sources	3
Beta strandⁱ	211 – 216	Combined sources	6
Helixⁱ	220 – 229	Combined sources	10
Helixⁱ	231 – 236	Combined sources	6

Show more details

3D structure databases

SMRⁱ	Q99593
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	Q99593

EvolutionaryTraceⁱ

Q99593

Family & Domainsⁱ

Domainⁱ

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

Phylogenomic databases

eggNOGⁱ	KOG3585, Eukaryota
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00940000156506
HOGENOMⁱ	CLU_037025_1_0_1
InParanoidⁱ	Q99593
KEGG Orthology (KO) More...KOⁱ	K10179
OMAⁱ	QPSEFLY
Database of Orthologous Groups More...OrthoDBⁱ	344556at2759
PhylomeDBⁱ	Q99593
TreeFamⁱ	TF106341

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00182, TBOX, 1 hit
Gene3Dⁱ	2.60.40.820, 1 hit
InterProⁱ	View protein in InterPro IPR008967, p53-like_TF_DNA-bd IPR036960, T-box_sf IPR001699, TF_T-box IPR018186, TF_T-box_CS
PANTHERⁱ	PTHR11267, PTHR11267, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00907, T-box, 1 hit
PRINTSⁱ	PR00937, TBOX
SMARTⁱ	View protein in SMART SM00425, TBOX, 1 hit
SUPFAMⁱ	SSF49417, SSF49417, 1 hit
PROSITEⁱ	View 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. Align Add to basket

Isoform 1 (identifier: Q99593-1) [UniParc]FASTA Add to basket

Also known as: Long

This isoform has been chosen as the canonicalⁱ 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]FASTA Add 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.

« 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 
SQDLLPPPNP YPLPQEHSQI YHCTKRKGEC DHPWSICFLS YLFLSLGWG

Show »

Length:349

Mass (Da):39,196

Checksum:ⁱ50CE556CD97ACD76

GO

Isoform 3 (identifier: Q99593-3) [UniParc]FASTA Add to basket

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

« Hide

        10         20         30         40         50
MEGIKVFLHE RELWLKFHEV GTEMIITKAG RRMFPSYKVK VTGLNPKTKY 
        60         70         80         90        100
ILLMDIVPAD DHRYKFADNK WSVTGKAEPA MPGRLYVHPD SPATGAHWMR 
       110        120        130        140        150
QLVSFQKLKL TNNHLDPFGH IILNSMHKYQ PRLHIVKADE NNGFGSKNTA 
       160        170        180        190        200
FCTHVFPETA FIAVTSYQNH KITQLKIENN PFAKGFRGSD DMELHRMSRM 
       210        220        230        240        250
QSKEYPVVPR STVRQKVASN HSPFSSESRA LSTSSNLGSQ YQCENGVSGP 
       260        270        280        290        300
SQDLLPPPNP YPLPQEHSQI YHCTKRKEEE CSTTDHPYKK PYMETSPSEE 
       310        320        330        340        350
DSFYRSSYPQ QQGLGASYRT ESAQRQACMY ASSAPPSEPV PSLEDISCNT 
       360        370        380        390        400
WPSMPSYSSC TVTTVQPMDR LPYQHFSAHF TSGPLVPRLA GMANHGSPQL 
       410        420        430        440        450
GEGMFQHQTS VAHQPVVRQC GPQTGLQSPG TLQPPEFLYS HGVPRTLSPH 
       460 
QYHSVHGVGM VPEWSDNS

Show »

Length:468

Mass (Da):52,659

Checksum:ⁱF0434B124BB31A5A

GO

Sequence cautionⁱ

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

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	7 – 49	GFGLA…AFTQQ → ALAGAHLWSLTQKTCLRFEP RARSGPPASPPGRPRSRLHP A in CAA70592 (PubMed:8988164).CuratedAdd BLAST	43
Sequence conflictⁱ	71	Missing in CAA70592 (PubMed:8988164).Curated	1
Sequence conflictⁱ	94	L → I in CAA70592 (PubMed:8988164).Curated	1
Sequence conflictⁱ	122	S → C in CAA70592 (PubMed:8988164).Curated	1
Sequence conflictⁱ	132	P → A in CAA70592 (PubMed:8988164).Curated	1
Sequence conflictⁱ	418 – 460	MDRLP…QHQTS → WTGYPTSTSPLTSPRGPWSL GWLAWQPWLPTAGRGNVPST RPP in CAA70592 (PubMed:8988164).CuratedAdd BLAST	43
Sequence conflictⁱ	468 – 470	RQC → SSV in CAA70592 (PubMed:8988164).Curated	3
Sequence conflictⁱ	494 – 518	PRTLS…WSDNS → QGLYPLISTTLCTELAWCRV ERQ in CAA70592 (PubMed:8988164).CuratedAdd BLAST	25

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_015381	49	Q → K in HOS. 1 PublicationCorresponds to variant dbSNP:rs104894383EnsemblClinVar.	1
Natural variantⁱVAR_015382	54	I → T in HOS. 1 PublicationCorresponds to variant dbSNP:rs104894384EnsemblClinVar.	1
Natural variantⁱVAR_009701	80	G → 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_076673	132	P → S Probable disease-associated variant found in a patient with atrial fibrillation; reduces transcriptional activity; affects transcriptional regulation of NKX2-5. 1 Publication	1
Natural variantⁱVAR_074599	143	A → T Probable disease-associated variant 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_074600	154	S → A Probable disease-associated variant found in patients with familial dilated cardiomyopathy; associated with disease susceptibility; associated with significantly decreased transcriptional activity. 1 Publication	1
Natural variantⁱVAR_076642	170	H → D Probable disease-associated variant found in a patient with atrial fibrillation; reduces transcriptional activity; affects transcriptional regulation of NKX2-5 or GATA4. 1 Publication	1
Natural variantⁱVAR_007456	237	R → Q in HOS; extensive upper limb malformations; affects transcriptional regulation of MYH6. 3 PublicationsCorresponds to variant dbSNP:rs104894378EnsemblClinVar.	1
Natural variantⁱVAR_009702	237	R → W in HOS; extensive upper limb malformations; strongly reduced affinity for DNA. 2 PublicationsCorresponds to variant dbSNP:rs104894382EnsemblClinVar.	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Length
Alternative sequenceⁱVSP_046845	1 – 50	Missing in isoform 3. 1 PublicationAdd BLAST	50
Alternative sequenceⁱVSP_006387	328 – 349	EEECS…TSPSE → GECDHPWSICFLSYLFLSLG WG in isoform 2. 1 PublicationAdd BLAST	22
Alternative sequenceⁱVSP_006388	350 – 518	Missing in isoform 2. 1 PublicationAdd BLAST	169

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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS9173.1 [Q99593-1] CCDS9174.1 [Q99593-3]
NCBI Reference Sequences More...RefSeqⁱ	NP_000183.2, NM_000192.3 [Q99593-1] NP_542448.1, NM_080717.2 [Q99593-3] NP_852259.1, NM_181486.2 [Q99593-1]

Genome annotation databases

Ensemblⁱ	ENST00000310346; ENSP00000309913; ENSG00000089225 [Q99593-1] ENST00000349716; ENSP00000337723; ENSG00000089225 [Q99593-3] ENST00000405440; ENSP00000384152; ENSG00000089225 [Q99593-1] ENST00000526441; ENSP00000433292; ENSG00000089225 [Q99593-2]
GeneIDⁱ	6910
KEGGⁱ	hsa:6910
UCSC genome browser More...UCSCⁱ	uc001tvo.5, human [Q99593-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q99593	TBX5 isoform 1		PONAB		518	UniRef100_Q99593
Uncharacterized protein		RHIRO		518
T-box transcription factor 5		CHLSB		518
T-box transcription factor 5		GORGO		518
Uncharacterized protein		RHIBE		518
+6

Protein	Similar proteins		Species	Score	Length	Source
Q99593	TBX5 isoform 1		PONAB		518	UniRef90_Q99593
Uncharacterized protein		RHIRO		518
T-box transcription factor 5		CHLSB		518
T-box transcription factor 5		GORGO		518
Uncharacterized protein		RHIBE		518
+27
Q99593-2	TBX5 isoform 4		PONAB		361	UniRef90_Q99593-2
Uncharacterized protein		RHIRO		349
TBX5 isoform 5		PANTR		349
Uncharacterized protein		AOTNA		348
Uncharacterized protein		CALJA		348
+5

Protein	Similar proteins		Species	Score	Length	Source
Q99593	TBX5 isoform 1		PONAB		518	UniRef50_Q99593
Uncharacterized protein		RHIRO		518
T-box transcription factor 5		CHLSB		518
T-box transcription factor 5		GORGO		518
Uncharacterized protein		RHIBE		518
+253
Q99593-2	TBX5 isoform 4		PONAB		361	UniRef50_Q99593-2
TBX5 isoform 5		PANTR		349
Uncharacterized protein		RHIRO		349
Uncharacterized protein		AOTNA		348
Uncharacterized protein		CALJA		348
+20

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
CCDSⁱ	CCDS9173.1 [Q99593-1] CCDS9174.1 [Q99593-3]
RefSeqⁱ	NP_000183.2, NM_000192.3 [Q99593-1] NP_542448.1, NM_080717.2 [Q99593-3] NP_852259.1, NM_181486.2 [Q99593-1]

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	2X6U	X-ray	1.90	A	51-251	[»]
	2X6V	X-ray	2.20	A/B	51-251	[»]
	4S0H	X-ray	2.82	A/E	53-238	[»]
	5BQD	X-ray	2.58	A/B	1-239	[»]
SMRⁱ	Q99593
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Protein-protein interaction databases

BioGRIDⁱ	112773, 9 interactors
CORUMⁱ	Q99593
IntActⁱ	Q99593, 9 interactors
STRINGⁱ	9606.ENSP00000309913

Chemistry databases

ChEMBLⁱ	CHEMBL1687681

ChEMBLⁱ

CHEMBL1687681

PTM databases

iPTMnetⁱ	Q99593
PhosphoSitePlusⁱ	Q99593

Polymorphism and mutation databases

BioMutaⁱ	TBX5
DMDMⁱ	12644474

Proteomic databases

jPOSTⁱ	Q99593
MassIVEⁱ	Q99593
PaxDbⁱ	Q99593
PeptideAtlasⁱ	Q99593
PRIDEⁱ	Q99593
ProteomicsDBⁱ	78347 [Q99593-1] 78348 [Q99593-2] 886

Protocols and materials databases

ABCDⁱ	Q99593, 6 sequenced antibodies
Antibodypediaⁱ	18791, 257 antibodies
The DNASU plasmid repository More...DNASUⁱ	6910

Genome annotation databases

Ensemblⁱ	ENST00000310346; ENSP00000309913; ENSG00000089225 [Q99593-1] ENST00000349716; ENSP00000337723; ENSG00000089225 [Q99593-3] ENST00000405440; ENSP00000384152; ENSG00000089225 [Q99593-1] ENST00000526441; ENSP00000433292; ENSG00000089225 [Q99593-2]
GeneIDⁱ	6910
KEGGⁱ	hsa:6910
UCSCⁱ	uc001tvo.5, human [Q99593-1]

Organism-specific databases

CTDⁱ	6910
DisGeNETⁱ	6910
EuPathDBⁱ	HostDB:ENSG00000089225.19
GeneCardsⁱ	TBX5
GeneReviewsⁱ	TBX5
HGNCⁱ	HGNC:11604, TBX5
HPAⁱ	ENSG00000089225, Tissue enhanced (heart muscle, lung, placenta)
MalaCardsⁱ	TBX5
MIMⁱ	142900, phenotype 601620, gene
neXtProtⁱ	NX_Q99593
OpenTargetsⁱ	ENSG00000089225
Orphanetⁱ	392, Holt-Oram syndrome
PharmGKBⁱ	PA36367
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG3585, Eukaryota
GeneTreeⁱ	ENSGT00940000156506
HOGENOMⁱ	CLU_037025_1_0_1
InParanoidⁱ	Q99593
KOⁱ	K10179
OMAⁱ	QPSEFLY
OrthoDBⁱ	344556at2759
PhylomeDBⁱ	Q99593
TreeFamⁱ	TF106341

Enzyme and pathway databases

PathwayCommonsⁱ	Q99593
Reactomeⁱ	R-HSA-2032785, YAP1- and WWTR1 (TAZ)-stimulated gene expression R-HSA-5578768, Physiological factors
SIGNORⁱ	Q99593

Miscellaneous databases

BioGRID-ORCSⁱ	6910, 5 hits in 897 CRISPR screens
ChiTaRSⁱ	TBX5, human
EvolutionaryTraceⁱ	Q99593
GeneWikiⁱ	TBX5_(gene)
GenomeRNAiⁱ	6910
Pharosⁱ	Q99593, Tbio
Protein Ontology More...PROⁱ	PR:Q99593
RNActⁱ	Q99593, protein
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000089225, Expressed in tendon of biceps brachii and 127 other tissues
Genevisibleⁱ	Q99593, HS

Family and domain databases

CDDⁱ	cd00182, TBOX, 1 hit
Gene3Dⁱ	2.60.40.820, 1 hit
InterProⁱ	View protein in InterPro IPR008967, p53-like_TF_DNA-bd IPR036960, T-box_sf IPR001699, TF_T-box IPR018186, TF_T-box_CS
PANTHERⁱ	PTHR11267, PTHR11267, 1 hit
Pfamⁱ	View protein in Pfam PF00907, T-box, 1 hit
PRINTSⁱ	PR00937, TBOX
SMARTⁱ	View protein in SMART SM00425, TBOX, 1 hit
SUPFAMⁱ	SSF49417, SSF49417, 1 hit
PROSITEⁱ	View protein in PROSITE PS01283, TBOX_1, 1 hit PS01264, TBOX_2, 1 hit PS50252, TBOX_3, 1 hit
ProtoNetⁱ	Search...
MobiDBⁱ	Search...

Entry informationⁱ

Entry nameⁱ	TBX5_HUMAN
Accessionⁱ	Q99593Primary (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:	October 7, 2020
	This is version 198 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	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.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Reference proteome

Documents

Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations

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UniProtKB - Q99593 (TBX5_HUMAN)

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T-box transcription factor TBX5

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

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Amino acid modifications

Keywords - PTMi

Proteomic databases

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<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

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<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Q99593

Isoform 1 [Q99593-1]

GO - Molecular functioni

Protein-protein interaction databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

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3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Phylogenomic databases

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<p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

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Keywords - Coding sequence diversityi

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Chemistry databases

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Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

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Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence cautionⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ