Homo sapiens Protein: TP63
InnateDB Protein IDBP-69495.7
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol TP63
Protein Name tumor protein p63
Synonyms AIS; B(p51A); B(p51B); EEC3; KET; LMS; NBP; OFC8; p40; p51; p53CP; p63; p73H; p73L; RHS; SHFM4; TP53CP; TP53L; TP73L;
Species Homo sapiens
Ensembl Protein ENSP00000346614
InnateDB Gene IDBG-69487 (TP63)
Protein Structure
UniProt Annotation
Function Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter. {ECO:0000269PubMed:11641404, ECO:0000269PubMed:12374749, ECO:0000269PubMed:12446779, ECO:0000269PubMed:12446784, ECO:0000269PubMed:20123734, ECO:0000269PubMed:22197488, ECO:0000269PubMed:9774969}.
Subcellular Localization Nucleus {ECO:0000269PubMed:12446779, ECO:0000269PubMed:20123734}.
Disease Associations Acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) [MIM:103285]: A form of ectodermal dysplasia. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. ADULT syndrome involves ectrodactyly, syndactyly, finger- and toenail dysplasia, hypoplastic breasts and nipples, intensive freckling, lacrimal duct atresia, frontal alopecia, primary hypodontia and loss of permanent teeth. ADULT syndrome differs significantly from EEC3 syndrome by the absence of facial clefting. {ECO:0000269PubMed:11929852}. Note=The disease is caused by mutations affecting the gene represented in this entry.Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) [MIM:106260]: An autosomal dominant condition characterized by congenital ectodermal dysplasia with coarse, wiry, sparse hair, dystrophic nails, slight hypohidrosis, scalp infections, ankyloblepharon filiform adnatum, maxillary hypoplasia, hypodontia and cleft lip/palate. {ECO:0000269PubMed:11159940}. Note=The disease is caused by mutations affecting the gene represented in this entry.Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3) [MIM:604292]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. It is an autosomal dominant syndrome characterized by ectrodactyly of hands and feet, ectodermal dysplasia and facial clefting. {ECO:0000269PubMed:10535733, ECO:0000269PubMed:10839977, ECO:0000269PubMed:11462173, ECO:0000269PubMed:12838557}. Note=The disease is caused by mutations affecting the gene represented in this entry.Split-hand/foot malformation 4 (SHFM4) [MIM:605289]: A limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients have been found to have mental retardation, ectodermal and craniofacial findings, and orofacial clefting. {ECO:0000269PubMed:10839977, ECO:0000269PubMed:11462173}. Note=The disease is caused by mutations affecting the gene represented in this entry.Limb-mammary syndrome (LMS) [MIM:603543]: Characterized by ectrodactyly, cleft palate and mammary-gland abnormalities. {ECO:0000269PubMed:11462173}. Note=The disease is caused by mutations affecting the gene represented in this entry.Note=Defects in TP63 are a cause of cervical, colon, head and neck, lung and ovarian cancers.Ectodermal dysplasia, Rapp-Hodgkin type (EDRH) [MIM:129400]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by the combination of anhidrotic ectodermal dysplasia, cleft lip, and cleft palate. The clinical syndrome is comprised of a characteristic facies (narrow nose and small mouth), wiry, slow-growing, and uncombable hair, sparse eyelashes and eyebrows, obstructed lacrimal puncta/epiphora, bilateral stenosis of external auditory canals, microsomia, hypodontia, cone-shaped incisors, enamel hypoplasia, dystrophic nails, and cleft lip/cleft palate. {ECO:0000269PubMed:12766194, ECO:0000269PubMed:12939657, ECO:0000269PubMed:15200513, ECO:0000269PubMed:16740912}. Note=The disease is caused by mutations affecting the gene represented in this entry.Non-syndromic orofacial cleft 8 (OFC8) [MIM:129400]: A birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. Note=The disease is caused by mutations affecting the gene represented in this entry.
Tissue Specificity Widely expressed, notably in heart, kidney, placenta, prostate, skeletal muscle, testis and thymus, although the precise isoform varies according to tissue type. Progenitor cell layers of skin, breast, eye and prostate express high levels of DeltaN-type isoforms. Isoform 10 is predominantly expressed in skin squamous cell carcinomas, but not in normal skin tissues. {ECO:0000269PubMed:11248048, ECO:0000269PubMed:9774969}.
Number of Interactions This gene and/or its encoded proteins are associated with 159 experimentally validated interaction(s) in this database.
They are also associated with 7 interaction(s) predicted by orthology.
Experimentally validated
Total 159 [view]
Protein-Protein 138 [view]
Protein-DNA 17 [view]
Protein-RNA 0
DNA-DNA 3 [view]
RNA-RNA 1 [view]
Predicted by orthology
Total 7 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0002039 p53 binding
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003684 damaged DNA binding
GO:0003690 double-stranded DNA binding
GO:0003700 sequence-specific DNA binding transcription factor activity
GO:0005515 protein binding
GO:0042802 identical protein binding
GO:0043565 sequence-specific DNA binding
GO:0044212 transcription regulatory region DNA binding
GO:0046872 metal ion binding
GO:0050699 WW domain binding
Biological Process
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006915 apoptotic process
GO:0006974 cellular response to DNA damage stimulus
GO:0006978 DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
GO:0007219 Notch signaling pathway
GO:0010165 response to X-ray
GO:0010332 response to gamma radiation
GO:0010482 regulation of epidermal cell division
GO:0031571 mitotic G1 DNA damage checkpoint
GO:0034644 cellular response to UV
GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0043523 regulation of neuron apoptotic process
GO:0045087 innate immune response (InnateDB)
GO:0045669 positive regulation of osteoblast differentiation
GO:0045747 positive regulation of Notch signaling pathway
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0051262 protein tetramerization
GO:0051289 protein homotetramerization
GO:0061436 establishment of skin barrier
GO:1902808 positive regulation of cell cycle G1/S phase transition
GO:2000271 positive regulation of fibroblast apoptotic process
GO:2000773 negative regulation of cellular senescence
Cellular Component
GO:0000785 chromatin
GO:0000790 nuclear chromatin
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005667 transcription factor complex
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0030425 dendrite
Protein Structure and Domains
InterPro IPR001660 Sterile alpha motif domain
IPR002117 p53 tumour suppressor family
IPR008967 p53-like transcription factor, DNA-binding
IPR010991 p53, tetramerisation domain
IPR011510 Sterile alpha motif, type 2
IPR011615 p53, DNA-binding domain
IPR013761 Sterile alpha motif/pointed domain
PFAM PF07710
Post-translational Modifications
SwissProt Q9H3D4
PhosphoSite PhosphoSite-Q9H3D4
UniProt Splice Variant
Entrez Gene 8626
UniGene Hs.137569
RefSeq NP_001108452
OMIM 603273
HPRD 04469
EMBL AB010153 AB016072 AB016073 AB042841 AF061512 AF075428 AF075429 AF075430 AF075431 AF075432 AF075433 AF091627 AF116756 AF116757 AF116758 AF116759 AF116760 AF116761 AF116762 AF116763 AF116764 AF116765 AF116766 AF116767 AF116768 AF116769 AF116770 AF116771 AF124528 AF124529 AF124530 AF124531 AF124532 AF124533 AF124534 AF124535 AF124536 AF124537 AF124538 AF124539 AF124540 AJ315499 AY339663 AY339664 AY341142 AY341143 AY341144 AY341145 AY342152 AY342153 AY342154 BC039815 GQ202689 Y16961
GenPept AAC24830 AAC43038 AAC62633 AAC62634 AAC62635 AAC62636 AAC62637 AAC62638 AAF43486 AAF43487 AAF43488 AAF43489 AAF43490 AAF43491 AAF43492 AAF43493 AAF61624 AAG45607 AAG45608 AAG45609 AAG45610 AAG45611 AAG45612 AAH39815 AAQ63448 AAQ63449 AAQ63450 AAQ63451 AAQ63452 AAQ63453 AAQ63454 ACV53609 BAA32433 BAA32592 BAA32593 BAB20591 CAA76562 CAC48053