Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol TP63 contributors: mct/pgu - updated : 06-03-2017
HGNC name tumor protein p63
HGNC id 15979
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one transactivation domain
  • a DNA binding region, including four subdomains (II-V), the p63DBD
  • at the C terminus a domain known to interact with other proteins, the sterile alpha motif (SAM), followed by a transcription inhibitory domain (TID)
    • mono polymer homomer , tetramer
    HOMOLOGY
    interspecies homolog to murine Trp63 (98.4pc)
    homolog to rattus Trp63 (97.8pc)
    intraspecies homolog to TP53
    Homologene
    FAMILY
  • p53 family
    • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • playing a critical role in the maintenance of the progenitor-cell populations necessary to sustain ectodermal differentiation (median apical ectodermal ridge, AER) development and morphogenesis, essential for regenerative proliferation in limb, craniofacial and epithelial development
  • involved in Notch signaling by probably inducing JAG1 and JAG2
  • playing a role in the regulation of epithelial morphogenesis
  • required for limb formation from the apical ectodermal ridge
  • may play a critical role in the progression of urothelial neoplasia
  • inhibit keratinocyte terminal differentiation during early development and play important roles in maintaining the epidermal stem cell population
  • acts upstream of DLX3 homeobox gene in a transcriptional regulatory pathway relevant to ectodermal dysplasia
  • essential for Ras-induced senescence
  • function as tumour suppressors by regulating senescence through TP53-independent pathways
  • is essential in a process of DNA damage-induced oocyte death not involving TP53
  • multi-isoform TP53 family member essential for epidermal development
  • binds to and transactivates the DICER1 promoter, demonstrating direct transcriptional regulation of DICER1 by TAP63
  • critical regulator of cancer metastasis
  • involved in promoting the repair of doxorubicin-induced DNA damage through arresting the cells at G0/G1
  • inducible in TP53-deficient cells by treatment with DNA-damaging agents and is involved in growth arrest, cell cycle regulation, and DNA damage repair
  • TP63 and SFN play opposing roles in the development of skin tumors and the accumulation of TP63 is essential for Ras/SFN mutation-induced papilloma formation and squamous cell carcinoma carcinogenesis
  • master regulator of epidermal morphogenesis, executing its function in part by directly regulating expression of the genome organizer SATB1 in progenitor cells
  • TP63 acts via transcriptional induction of the BH3-only proteins, BBC3 and PMAIP1 to cause apoptosis of DNA-damaged primordial follicle oocytes
  • TP63 is a crucial regulator of a subset of desmosomal genes
  • involved in bladder exstrophy epispadias complex (BEEC)
    • pathogenesis
    CELLULAR PROCESS cell life, cell death/apoptosis
    nucleotide, transcription, regulation
    nucleotide, RNA splicing
    PHYSIOLOGICAL PROCESS development
    text transcriptional coactivator
    PATHWAY
    metabolism
    signaling sensory transduction/vision
    a component
    INTERACTION
    DNA binding DNA as a homotetramer
    RNA
    small molecule metal binding,
  • binding ion Zn2+
    • protein
  • FMR1 (RNA target of FMR1)
  • interacting with AIRE (involvement of AIRE and TP63 in the regulation of HLA class II)
  • interacting with SHISA5 (TP63 target gene induced during epithelial differentiation, a complex process that also involves ER stress induction)
  • interacting with CCL17 (TP63 induces CD4+ T-cell chemoattractant CCL17 in human epithelial cells)
  • interacting with CDH3
  • directly associated with the DLX5 and DLX6 promoters
  • MIR130B is a direct target of TP63
  • antagonistic roles of POU2F3 and deltaNp63, probably through competition for overlapping binding sites or through an indirect interaction
  • phosphorylated TP63 induces transcription of ADRM1, leading to NOS2 protein degradation
  • binding specific cis-acting sequence within the ID2 gene promoter, not suppressing ID2 expression, but rather preventing excessive expression of that protein to enable the onset of keratinocyte differentiation
  • ZNF750 is a direct target of TP63
  • TP63 but not TP53 is essential for DNA damage triggered transcriptional induction of BBC3 and PMAIP1 in primordial follicle oocytes
  • RNF144B is a potentially critical component of epithelial homeostasis, acting downstream of TP63 to regulate cellular levels of CDKN1A and TP63
  • FANCD2 activates transcription of TP63 and suppresses tumorigenesis
  • RBM24 is a novel regulator of TP63 via mRNA stability (TP63 is regulated by RBM24 via mRNA stability)
  • TRIM29 regulates the TP63-mediated pathway and the behavior of cervical cancer cells
  • MTSS1/TP63 axis might be functionally important to regulate breast tumor progression
  • like CLCA2, MPZL2 is a type I transmembrane protein that is regulated by TP53 and TP63
    • cell & other
    REGULATION
    induced by induced in association with the upregulation and a secretion of growth differentiation factor 15 (GDF15) during the keratinocyte differentiation
    Other its phosphorylation is induced by DNA damage
    phosphorylated by PLK1, resulting in a decrease of stability and suppression of TP63-induced cell death in liver tumor cells
    regulated via mRNA stability and a novel regulatory feedback loop between RBM38 and TP63
    ASSOCIATED DISORDERS
    corresponding disease(s) AEC , LMS , SHFM4 , ADULT , RHS , EEC3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation     gain of function
    mutation gain of function in ADULT syndrome
    tumoral       loss of function
    in squamous cell carcinoma
    tumoral somatic mutation      
    in B cell lymphoma
    constitutional germinal mutation      
    in Hay-Wells syndrome
    constitutional     --other  
    dysregulated in psoriasis
    tumoral     --low  
    in cancer showed an increased invasive ability
    tumoral     --over  
    in 80 p100 of head and neck squamous cell carcinomas (HNSCC)
    tumoral     --over  
    in two TP53-deficient human cancer cell lines, leading to cell cycle arrest and attenuating doxorubicin-induced DNA damage
    tumoral     --low  
    in TP53-expressing cancer cells, possibly due to their similar biological functions
    tumoral fusion      
    fusion between TBL1XR1 and TP63,in diffuse large B-cell lymphoma (DLBCL)
    tumoral   amplification    
    in early stage of esophageal squamous cell carcinoma (EC-SCC) carcinogenesis but down-regulated in advanced stage of disease
    Susceptibility
  • to urinary bladder cancer
  • to nonsyndromic cleft palate and nonsyndromic cleft lip and palate
  • to bladder exstrophy epispadias complex
    • Variant & Polymorphism insertion/deletion , other
  • increasing the risk of urinary bladder cancer
  • a SAM domain mutation (p.Asp564His) in TP63 that predisposed the patients to have nonsyndromic cleft palate and nonsyndromic cleft lip and palate
  • Insertion/deletion polymorphisms in the deltaNp63 promoter are a risk factor for bladder exstrophy epispadias complex
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    potential target of anti-cancer therapy for human malignancies with compromised TP53
    ANIMAL & CELL MODELS
  • p63-null mice revealed a complex relationship between the gene and development, with severe deleterious effects
  • mice lacking p63 exhibit skin and craniofacial defects including cleft palate