ID:P63_HUMAN DESCRIPTION: RecName: Full=Tumor protein 63; Short=p63; AltName: Full=Chronic ulcerative stomatitis protein; Short=CUSP; AltName: Full=Keratinocyte transcription factor KET; AltName: Full=Transformation-related protein 63; Short=TP63; AltName: Full=Tumor protein p73-like; Short=p73L; AltName: Full=p40; AltName: Full=p51; 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. COFACTOR: Binds 1 zinc ion per subunit (By similarity). SUBUNIT: Binds DNA as a homotetramer. Isoform composition of the tetramer may determine transactivation activity. Isoforms Alpha and Gamma interact with HIPK2. Interacts with SSRP1, leading to stimulate coactivator activity. Isoform 1 and isoform 2 interact with WWP1. Interacts with PDS5A. Isoform 5 (via activation domain) interacts with NOC2L. INTERACTION: P35637:FUS; NbExp=2; IntAct=EBI-2337775, EBI-400434; P61978:HNRNPK; NbExp=2; IntAct=EBI-2337775, EBI-304185; Q9UFN0:NIPSNAP3A; NbExp=2; IntAct=EBI-2337775, EBI-716291; Q15796:SMAD2; NbExp=3; IntAct=EBI-2337775, EBI-1040141; P04637:TP53; NbExp=5; IntAct=EBI-2337775, EBI-366083; SUBCELLULAR LOCATION: Nucleus. 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. DOMAIN: The transactivation inhibitory domain (TID) can interact with, and inhibit the activity of the N-terminal transcriptional activation domain of TA*-type isoforms. PTM: May be sumoylated (By similarity). PTM: Ubiquitinated. Polyubiquitination involves WWP1 and leads to proteasomal degradation of this protein. DISEASE: Defects in TP63 are the cause of acro-dermato-ungual- lacrimal-tooth syndrome (ADULT syndrome) [MIM:103285]; a form of ectodermal dysplasia. Ectodermal dysplasias (EDs) constitute a heterogeneous group of developmental disorders affecting tissues of ectodermal origin. EDs are characterized by abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. 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 differs significantly from EEC3 syndrome by the absence of facial clefting. DISEASE: Defects in TP63 are the cause of ankyloblepharon- ectodermal defects-cleft lip/palate (AEC) [MIM:106260]. AEC is 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. DISEASE: Defects in TP63 are the cause of ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome type 3 (EEC3) [MIM:604292]. EEC3 is an autosomal dominant syndrome characterized by ectrodactyly of hands and feet, ectodermal dysplasia and facial clefting. DISEASE: Defects in TP63 are the cause of split-hand/foot malformation type 4 (SHFM4) [MIM:605289]. Split-hand/split-foot malformation is 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. There is restricted overlap between the mutational spectra of EEC3 and SHFM4. DISEASE: Defects in TP63 are the cause of limb-mammary syndrome (LMS) [MIM:603543]. LMS is characterized by ectrodactyly, cleft palate and mammary-gland abnormalities. DISEASE: Note=Defects in TP63 are a cause of cervical, colon, head and neck, lung and ovarian cancers. DISEASE: Defects in TP63 are a cause of ectodermal dysplasia Rapp- Hodgkin type (EDRH) [MIM:129400]; also called Rapp-Hodgkin syndrome or anhidrotic ectodermal dysplasia with cleft lip/palate. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDRH is 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. DISEASE: Defects in TP63 are the cause of non-syndromic orofacial cleft type 8 (OFC8) [MIM:129400]. Non-syndromic orofacial cleft is a common 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. SIMILARITY: Belongs to the p53 family. SIMILARITY: Contains 1 SAM (sterile alpha motif) domain. SEQUENCE CAUTION: Sequence=AAF43486.1; Type=Erroneous initiation; Sequence=AAF43487.1; Type=Erroneous initiation; Sequence=AAF43488.1; Type=Erroneous initiation; Sequence=AAF43489.1; Type=Erroneous initiation; Sequence=AAF61624.1; Type=Frameshift; Positions=26; Sequence=BAA32592.1; Type=Frameshift; Positions=26; Sequence=BAA32593.1; Type=Frameshift; Positions=26; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TP63";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9H3D4
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0000989 transcription factor activity, transcription factor binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding 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 transcription factor activity, sequence-specific DNA binding GO:0005515 protein binding GO:0019904 protein domain specific 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 GO:0097371 MDM2/MDM4 family protein binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0001302 replicative cell aging GO:0001501 skeletal system development GO:0001736 establishment of planar polarity GO:0001738 morphogenesis of a polarized epithelium GO:0001942 hair follicle development GO:0002053 positive regulation of mesenchymal cell proliferation GO:0002064 epithelial cell development GO:0006338 chromatin remodeling GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006366 transcription from RNA polymerase II promoter 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:0007275 multicellular organism development GO:0007283 spermatogenesis GO:0007389 pattern specification process GO:0007499 ectoderm and mesoderm interaction GO:0007568 aging GO:0007569 cell aging GO:0008283 cell proliferation GO:0008544 epidermis development GO:0009887 animal organ morphogenesis GO:0009913 epidermal cell differentiation GO:0009954 proximal/distal pattern formation GO:0010165 response to X-ray GO:0010259 multicellular organism aging GO:0010332 response to gamma radiation GO:0010481 epidermal cell division GO:0010482 regulation of epidermal cell division GO:0010838 positive regulation of keratinocyte proliferation GO:0030154 cell differentiation GO:0030216 keratinocyte differentiation GO:0030326 embryonic limb morphogenesis GO:0030850 prostate gland development GO:0030855 epithelial cell differentiation GO:0030859 polarized epithelial cell differentiation GO:0031069 hair follicle morphogenesis GO:0031571 mitotic G1 DNA damage checkpoint GO:0032502 developmental process GO:0033147 negative regulation of intracellular estrogen receptor signaling pathway GO:0034644 cellular response to UV GO:0035115 embryonic forelimb morphogenesis GO:0035116 embryonic hindlimb morphogenesis GO:0036342 post-anal tail morphogenesis GO:0042475 odontogenesis of dentin-containing tooth GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator GO:0042981 regulation of apoptotic process GO:0043066 negative regulation of apoptotic process GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043523 regulation of neuron apoptotic process GO:0043589 skin morphogenesis GO:0043616 keratinocyte proliferation GO:0045617 negative regulation of keratinocyte differentiation 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:0048485 sympathetic nervous system development GO:0048646 anatomical structure formation involved in morphogenesis GO:0048745 smooth muscle tissue development GO:0048807 female genitalia morphogenesis GO:0051262 protein tetramerization GO:0051289 protein homotetramerization GO:0051402 neuron apoptotic process GO:0060157 urinary bladder development GO:0060197 cloacal septation GO:0060513 prostatic bud formation GO:0060529 squamous basal epithelial stem cell differentiation involved in prostate gland acinus development GO:0061436 establishment of skin barrier GO:0098773 skin epidermis development GO:1900740 positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway GO:1901796 regulation of signal transduction by p53 class mediator GO:1902808 positive regulation of cell cycle G1/S phase transition GO:1904674 positive regulation of somatic stem cell population maintenance GO:1904888 cranial skeletal system development GO:2000271 positive regulation of fibroblast apoptotic process GO:2000381 negative regulation of mesoderm development GO:2000773 negative regulation of cellular senescence GO:2001235 positive regulation of apoptotic signaling pathway
AF061512 - Homo sapiens p53 homolog (p40) mRNA, complete cds. LQ270756 - Sequence 84 from Patent WO2016071350. BC039815 - Homo sapiens tumor protein p63, mRNA (cDNA clone MGC:48678 IMAGE:5552611), complete cds. LQ270754 - Sequence 82 from Patent WO2016071350. LQ270764 - Sequence 92 from Patent WO2016071350. AB016072 - Homo sapiens mRNA for p51A, complete cds. AB016073 - Homo sapiens mRNA for p51B, complete cds. AF116771 - Homo sapiens p51 delta mRNA, complete cds. Y16961 - Homo sapiens mRNA for KET protein. KJ892577 - Synthetic construct Homo sapiens clone ccsbBroadEn_01971 TP63 gene, encodes complete protein. KR711023 - Synthetic construct Homo sapiens clone CCSBHm_00019213 TP63 (TP63) mRNA, encodes complete protein. KR711024 - Synthetic construct Homo sapiens clone CCSBHm_00019243 TP63 (TP63) mRNA, encodes complete protein. KR711025 - Synthetic construct Homo sapiens clone CCSBHm_00019247 TP63 (TP63) mRNA, encodes complete protein. CU691766 - Synthetic construct Homo sapiens gateway clone IMAGE:100021252 5' read TP63 mRNA. KU178435 - Homo sapiens tumor protein p63 isoform 1 (TP63) mRNA, partial cds. KU178436 - Homo sapiens tumor protein p63 isoform 2 (TP63) mRNA, partial cds, alternatively spliced. EU446669 - Synthetic construct Homo sapiens clone IMAGE:100070360; IMAGE:100011878; FLH257254.01L tumor protein p63 (TP63) gene, encodes complete protein. AF075428 - Homo sapiens TA p63 gamma mRNA, complete cds. AF075432 - Homo sapiens TA p63 beta mRNA, complete cds. AF075430 - Homo sapiens TA p63 alpha mRNA, complete cds. LQ270762 - Sequence 90 from Patent WO2016071350. AK304127 - Homo sapiens cDNA FLJ52400 complete cds, highly similar to Tumor protein p73-like. LQ270758 - Sequence 86 from Patent WO2016071350. LQ270760 - Sequence 88 from Patent WO2016071350. GQ202689 - Homo sapiens tumor protein p63 deltaN isoform epsilon (TP63) mRNA, complete cds. GQ202690 - Homo sapiens tumor protein p63 deltaN isoform delta (TP63) mRNA, complete cds. AF091627 - Homo sapiens CUSP mRNA, complete cds. AB010153 - Homo sapiens mRNA for p73H, complete cds. KP881229 - Homo sapiens tumor protein p63 (TP63) mRNA, complete cds, alternatively spliced. KP881230 - Homo sapiens tumor protein p63 (TP63) mRNA, complete cds, alternatively spliced. KP881231 - Homo sapiens tumor protein p63 (TP63) mRNA, complete cds, alternatively spliced. AF075429 - Homo sapiens DN p63 gamma mRNA, complete cds. AF075433 - Homo sapiens DN p63 beta mRNA, complete cds. AB042841 - Homo sapiens p73L/p63/p51/p40/KET mRNA for delta N p73L, complete cds. AF075431 - Homo sapiens DN p63 alpha mRNA, complete cds. AJ315499 - Homo sapiens partial mRNA for p63 delta (p63/p73L/p51/p40/KET gene). JD563772 - Sequence 544796 from Patent EP1572962. JD336439 - Sequence 317463 from Patent EP1572962. JD245847 - Sequence 226871 from Patent EP1572962. JD198693 - Sequence 179717 from Patent EP1572962. JD038579 - Sequence 19603 from Patent EP1572962. JD225303 - Sequence 206327 from Patent EP1572962. JD234770 - Sequence 215794 from Patent EP1572962. JD082351 - Sequence 63375 from Patent EP1572962. JD349380 - Sequence 330404 from Patent EP1572962. JD420058 - Sequence 401082 from Patent EP1572962. JD062922 - Sequence 43946 from Patent EP1572962. JD250229 - Sequence 231253 from Patent EP1572962. JD301714 - Sequence 282738 from Patent EP1572962. JD078454 - Sequence 59478 from Patent EP1572962. JD439803 - Sequence 420827 from Patent EP1572962. JD550801 - Sequence 531825 from Patent EP1572962. JD162634 - Sequence 143658 from Patent EP1572962. JD348868 - Sequence 329892 from Patent EP1572962. JD331486 - Sequence 312510 from Patent EP1572962. JD500332 - Sequence 481356 from Patent EP1572962. JD163455 - Sequence 144479 from Patent EP1572962. JD504557 - Sequence 485581 from Patent EP1572962. JD073242 - Sequence 54266 from Patent EP1572962. JD051479 - Sequence 32503 from Patent EP1572962. JD225161 - Sequence 206185 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q9H3D4 (Reactome details) participates in the following event(s):
R-HSA-5632393 TP63/TP53 bind the DDIT4 gene promoter R-HSA-6798082 TP53 family members bind the CASP1 gene R-HSA-6799761 TP53 binds PPP1R13L R-HSA-6799777 TP53 family members bind PPP1R13B or TP53BP2 R-HSA-6800836 TP53 or TP63 binds the PERP gene R-HSA-3700981 TP53 family members bind the BAX promoter R-HSA-4331340 TP53 binds the BBC3 (PUMA) promoter R-HSA-6799462 TP53 family members bind the TP53I3 (PIG3) gene promoter R-HSA-6799815 TP53 family members bind the FAS gene R-HSA-5628897 TP53 Regulates Metabolic Genes R-HSA-6803207 TP53 Regulates Transcription of Caspase Activators and Caspases R-HSA-6804759 Regulation of TP53 Activity through Association with Co-factors R-HSA-6803205 TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-6803204 TP53 Regulates Transcription of Genes Involved in Cytochrome C Release R-HSA-139915 Activation of PUMA and translocation to mitochondria R-HSA-6803211 TP53 Regulates Transcription of Death Receptors and Ligands R-HSA-5633008 TP53 Regulates Transcription of Cell Death Genes R-HSA-5633007 Regulation of TP53 Activity R-HSA-212436 Generic Transcription Pathway R-HSA-114452 Activation of BH3-only proteins R-HSA-73857 RNA Polymerase II Transcription R-HSA-109606 Intrinsic Pathway for Apoptosis R-HSA-74160 Gene expression (Transcription) R-HSA-109581 Apoptosis R-HSA-5357801 Programmed Cell Death
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
