TBX5

Protein identityUniProt · HPA

UniProt accession

Q99593

Gene

TBX5

Ensembl

ENSG00000089225

Chromosome

12

Canonical length

518 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene is closely linked to related family member T-box 3 (ulnar mammary syndrome) on human chromosome 12. The encoded protein may play a role in heart development and specification of limb identity. Mutations in this gene have been associated with Holt-Oram syndrome, a developmental disorder affecting the heart and upper limbs. Several transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

518 residues, UniProt reviewed canonical sequence.

>Q99593|TBX5
     1  MADADEGFGL AHTPLEPDAK DLPCDSKPES ALGAPSKSPS SPQAAFTQQG MEGIKVFLHE
    61  RELWLKFHEV GTEMIITKAG RRMFPSYKVK VTGLNPKTKY ILLMDIVPAD DHRYKFADNK
   121  WSVTGKAEPA MPGRLYVHPD SPATGAHWMR QLVSFQKLKL TNNHLDPFGH IILNSMHKYQ
   181  PRLHIVKADE NNGFGSKNTA FCTHVFPETA FIAVTSYQNH KITQLKIENN PFAKGFRGSD
   241  DMELHRMSRM QSKEYPVVPR STVRQKVASN HSPFSSESRA LSTSSNLGSQ YQCENGVSGP
   301  SQDLLPPPNP YPLPQEHSQI YHCTKRKEEE CSTTDHPYKK PYMETSPSEE DSFYRSSYPQ
   361  QQGLGASYRT ESAQRQACMY ASSAPPSEPV PSLEDISCNT WPSMPSYSSC TVTTVQPMDR
   421  LPYQHFSAHF TSGPLVPRLA GMANHGSPQL GEGMFQHQTS VAHQPVVRQC GPQTGLQSPG
   481  TLQPPEFLYS HGVPRTLSPH QYHSVHGVGM VPEWSDNS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TBX5 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.55

Highest tissue expression

74 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TBX5.

Disease | AllUniProt

Conditions TBX5 is implicated in, by any mechanism.

• Holt-Oram syndrome (HOS) MIM:142900

Disease | GeneticClinVar

196 pathogenic / likely-pathogenic of 846 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Holt-Oram syndrome
• Aortic valve disease 2
• Cardiovascular phenotype
• TBX5-related disorder
• Abnormal heart morphology

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.14

gnomAD pLI

1

gnomAD missense Z

1.19

DepMap mean gene effect

0

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• atrial septum morphogenesis
• atrioventricular bundle cell differentiation
• atrioventricular node cell development
• atrioventricular node cell fate commitment
• atrioventricular valve morphogenesis
• bundle of His cell to Purkinje myocyte communication by electrical coupling
• bundle of His development
• cardiac left ventricle formation
• cardiac muscle cell proliferation
• cell fate specification
• cell-cell signaling
• embryonic forelimb morphogenesis
• embryonic limb morphogenesis
• endocardial cushion development
• forelimb morphogenesis
• heart development
• lung development
• morphogenesis of an epithelium
• negative regulation of cardiac muscle cell proliferation
• negative regulation of cell migration
• negative regulation of cell population proliferation
• negative regulation of epithelial to mesenchymal transition
• pattern specification process
• pericardium development
• positive regulation of cardiac muscle cell proliferation
• positive regulation of cardioblast differentiation
• positive regulation of cell communication by electrical coupling involved in cardiac conduction
• positive regulation of DNA-templated transcription
• positive regulation of gap junction assembly
• positive regulation of secondary heart field cardioblast proliferation
• positive regulation of transcription by RNA polymerase II
• regulation of atrial cardiac muscle cell membrane depolarization
• regulation of transcription by RNA polymerase II
• sinoatrial node development
• transcription by RNA polymerase II
• ventricular septum development
• cell migration involved in coronary vasculogenesis
• positive regulation of cardiac conduction

Molecular functions

• DNA binding
• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity
• DNA-binding transcription factor activity, RNA polymerase II-specific
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• RNA polymerase II-specific DNA-binding transcription factor binding
• sequence-specific DNA binding

Cellular components

• chromatin
• cytoplasm
• nucleoplasm
• nucleus
• protein-containing complex
• protein-DNA complex
• transcription regulator complex

Protein domainsUniProt · Pfam · InterPro

• T-box transcription factor
• p53-like transcription factor, DNA-binding domain superfamily
• Transcription factor, T-box, conserved site
• T-box superfamily
• T-box transcription factor, DNA-binding domain
• T-box

KeywordsUniProt

• Acetylation
• Atrial fibrillation
• Cardiomyopathy
• Cytoplasm
• Developmental protein
• DNA-binding
• Nucleus
• Transcription
• Transcription regulation

InteractionsUniProt · HPA

Protein binding partners of TBX5 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GATA4
• KAT2A
• KAT2B
• PDLIM7