TP63

Protein identityUniProt · HPA

UniProt accession

Q9H3D4

Gene

TP63

Ensembl

ENSG00000073282

Chromosome

3

Canonical length

680 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm

Quaternary structure

Homotetramer

OverviewNCBI Gene

This gene encodes a member of the p53 family of transcription factors. The functional domains of p53 family proteins include an N-terminal transactivation domain, a central DNA-binding domain and an oligomerization domain. Alternative splicing of this gene and the use of alternative promoters results in multiple transcript variants encoding different isoforms that vary in their functional properties. These isoforms function during skin development and maintenance, adult stem/progenitor cell regulation, heart development and premature aging. Some isoforms have been found to protect the germline by eliminating oocytes or testicular germ cells that have suffered DNA damage. Mutations in this gene are associated with ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3); split-hand/foot malformation 4 (SHFM4); ankyloblepharon-ectodermal defects-cleft lip/palate; ADULT syndrome (acro-dermato-ungual-lacrimal-tooth); limb-mammary syndrome; Rap-Hodgkin syndrome (RHS); and orofacial cleft 8. [provided by RefSeq, Aug 2016]

Canonical amino-acid sequenceUniProt

680 residues, UniProt reviewed canonical sequence.

>Q9H3D4|TP63
     1  MNFETSRCAT LQYCPDPYIQ RFVETPAHFS WKESYYRSTM SQSTQTNEFL SPEVFQHIWD
    61  FLEQPICSVQ PIDLNFVDEP SEDGATNKIE ISMDCIRMQD SDLSDPMWPQ YTNLGLLNSM
   121  DQQIQNGSSS TSPYNTDHAQ NSVTAPSPYA QPSSTFDALS PSPAIPSNTD YPGPHSFDVS
   181  FQQSSTAKSA TWTYSTELKK LYCQIAKTCP IQIKVMTPPP QGAVIRAMPV YKKAEHVTEV
   241  VKRCPNHELS REFNEGQIAP PSHLIRVEGN SHAQYVEDPI TGRQSVLVPY EPPQVGTEFT
   301  TVLYNFMCNS SCVGGMNRRP ILIIVTLETR DGQVLGRRCF EARICACPGR DRKADEDSIR
   361  KQQVSDSTKN GDGTKRPFRQ NTHGIQMTSI KKRRSPDDEL LYLPVRGRET YEMLLKIKES
   421  LELMQYLPQH TIETYRQQQQ QQHQHLLQKQ TSIQSPSSYG NSSPPLNKMN SMNKLPSVSQ
   481  LINPQQRNAL TPTTIPDGMG ANIPMMGTHM PMAGDMNGLS PTQALPPPLS MPSTSHCTPP
   541  PPYPTDCSIV SFLARLGCSS CLDYFTTQGL TTIYQIEHYS MDDLASLKIP EQFRHAIWKG
   601  ILDHRQLHEF SSPSHLLRTP SSASTVSVGS SETRGERVID AVRFTLRQTI SFPPRDEWND
   661  FNFDMDARRN KQQRIKEEGE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TP63 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)

0.52

Highest tissue expression

130 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TP63.

Disease | AllUniProt

Conditions TP63 is implicated in, by any mechanism.

• Acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) MIM:103285
• Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) MIM:106260
• Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3) MIM:604292
• Split-hand/foot malformation 4 (SHFM4) MIM:605289
• Limb-mammary syndrome (LMS) MIM:603543
• Rapp-Hodgkin syndrome (RHS) MIM:129400
• Orofacial cleft 8 (OFC8) MIM:618149
• Premature ovarian failure 21 (POF21) MIM:620311

Disease | GeneticClinVar

132 pathogenic / likely-pathogenic of 837 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• TP63-Related Spectrum Disorders
• Ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3
• Rapp-Hodgkin syndrome
• Split hand-foot malformation 4
• TP63-related disorder

ReferencesPubMed · IEDB

Publications for TP63 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.27

gnomAD pLI

1

gnomAD missense Z

2.21

DepMap mean gene effect

-0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• apoptotic process
• cellular senescence
• chromatin remodeling
• cloacal septation
• cranial skeletal system development
• determination of adult lifespan
• DNA damage response
• embryonic forelimb morphogenesis
• embryonic hindlimb morphogenesis
• epithelial cell development
• establishment of planar polarity
• establishment of skin barrier
• female genitalia morphogenesis
• hair follicle morphogenesis
• intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
• keratinocyte differentiation
• keratinocyte proliferation
• negative regulation of cellular senescence
• negative regulation of DNA-templated transcription
• negative regulation of intracellular estrogen receptor signaling pathway
• negative regulation of keratinocyte differentiation
• negative regulation of mesoderm development
• negative regulation of transcription by RNA polymerase II
• neuron apoptotic process
• Notch signaling pathway
• odontogenesis of dentin-containing tooth
• polarized epithelial cell differentiation
• positive regulation of apoptotic signaling pathway
• positive regulation of cell cycle G1/S phase transition
• positive regulation of DNA-templated transcription
• positive regulation of fibroblast apoptotic process
• positive regulation of keratinocyte proliferation
• positive regulation of Notch signaling pathway
• positive regulation of osteoblast differentiation
• positive regulation of somatic stem cell population maintenance
• positive regulation of stem cell proliferation
• positive regulation of transcription by RNA polymerase II
• post-anal tail morphogenesis
• prostatic bud formation
• protein tetramerization
• proximal/distal pattern formation
• regulation of apoptotic process
• regulation of epidermal cell division
• skeletal system development
• skin morphogenesis
• spermatogenesis
• squamous basal epithelial stem cell differentiation involved in prostate gland acinus development
• stem cell proliferation
• sympathetic nervous system development
• transcription by RNA polymerase II
• ectoderm and mesoderm interaction
• epidermal cell division

Molecular functions

• chromatin binding
• damaged DNA binding
• 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
• identical protein binding
• MDM2/MDM4 family protein binding
• metal ion binding
• p53 binding
• promoter-specific chromatin binding
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• RNA polymerase II transcription regulatory region sequence-specific DNA binding
• WW domain binding

Cellular components

• chromatin
• cytoplasm
• dendrite
• nucleoplasm
• nucleus
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• Sterile alpha motif domain
• p53 tumour suppressor family
• p53-like transcription factor, DNA-binding domain superfamily
• p53, tetramerisation domain
• p53, DNA-binding domain
• p53/RUNT-type transcription factor, DNA-binding domain superfamily
• Sterile alpha motif/pointed domain superfamily
• p53-like tetramerisation domain superfamily
• p53, central conserved site
• P53 DNA-binding domain
• SAM domain (Sterile alpha motif)
• P53 tetramerisation motif
• Tumour protein p63, SAM domain

KeywordsUniProt

• Activator
• Alternative promoter usage
• Apoptosis
• Developmental protein
• DNA-binding
• Ectodermal dysplasia
• Isopeptide bond
• Metal-binding
• Notch signaling pathway
• Nucleus
• Premature ovarian failure
• Transcription
• Transcription regulation
• Ubl conjugation
• Zinc

InteractionsUniProt · HPA

Protein binding partners of TP63 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• NOC2L
• PDS5A
• SSRP1
• PPP1R13L
• HIPK2
• HNRNPAB
• ITCH
• NIPSNAP3A
• SATB2
• TP53
• TP73
• YAP1