InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TP63

Summary

InnateDB Protein

IDBP-245607.7

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

ENSP00000376256

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}.

Comments

Interactions

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]
DNA-RNA	0

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

PDB ID

InterPro

IPR002117 p53 tumour suppressor family
IPR008967 p53-like transcription factor, DNA-binding
IPR010991 p53, tetramerisation domain
IPR011615 p53, DNA-binding domain

PFAM

PF07710
PF00870

PRINTS

PR00386

PIRSF

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q9H3D4