two additional transcripts called delta-N-p63-delta and delta-N-p63-epsilon, that increase from 6 to 10 the number of the p63 isoforms (due to the 2 alternative promoters P1 and P2 and five variants) (PMID: 19700772)
identification
nb exons
type
bp
product
Protein
kDa
AA
specific expression
Year
Pubmed
14
-
4927
-
680
-
2009
19898465
also called TAp63alpha, KET and p51B
exons 2-14 with the transactivation domain
has little transactivation activity (PMID: 21075072)
13
-
4833
-
555
-
2009
19898465
also called TAp63beta (transcriptionally active (TA))
exons 2-12, 14, TA+, lacking the SAM domain
11
-
2870
-
487
-
2009
19898465
also called TAp63gamma
exons 2-10, 15, TA+ lacking the SAM domain
transactivates target genes in a manner similar to that of TP53 (PMID: 21075072)
12
-
4697
-
586
-
2009
19898465
also called deltaNp63alpha, CUSP and p73H
exons 3, 4-14
crucial for modulation of KRT14 transcription
plays a master role in epidermal development (PMID: 20888799)
the SAM domain appears, at least in part, to be involved in the inhibition of POU2F3
represses the transactivation activity of TP53 or TAp63gamma, but deltaNp63gamma can only repress the transactivation activity of TP53
lacking the N-terminal domain, and having a critical role in the maintenance of self renewal and progenitor capacity in several types of epithelial tissues
activation of the CTNNB1 pathway may contribute to overexpression of deltaNp63 during tumour progression, in a cell type-specific manner
11
-
4603
-
461
-
2009
19898465
also called deltaNp63beta
exons 3', 4-12, 14, TA- lacking the SAM domain
lacking the N-terminal domain, and having a critical role in the maintenance of self renewal and progenitor capacity in several types of epithelial tissues
activation of the CTNNB1 pathway may contribute to overexpression of deltaNp63 during tumour progression, in a cell type-specific manner
9
-
2640
-
393
-
2009
19898465
also called deltaNp63gamma
exons 3', 4-10, 15, TA- lacking the SAM domain
lacking the N-terminal domain, and having a critical role in the maintenance of self renewal and progenitor capacity in several types of epithelial tissues
activation of the CTNNB1 pathway may contribute to overexpression of deltaNp63 during tumour progression, in a cell type-specific manner
EXPRESSION
Type
widely
expressed in
(based on citations)
organ(s)
System
Organ level 1
Organ level 2
Organ level 3
Organ level 4
Level
Pubmed
Species
Stage
Rna symbol
Cardiovascular
heart
highly
Digestive
esophagus
moderately
mouth
predominantly
pharynx
highly
Reproductive
male system
male genital tract
moderately
Homo sapiens
Fetal
Respiratory
respiratory tract
larynx
highly
Skin/Tegument
skin
moderately
Homo sapiens
Fetal
Urinary
bladder
highly
Homo sapiens
Fetal
tissue
System
Tissue
Tissue level 1
Tissue level 2
Level
Pubmed
Species
Stage
Rna symbol
Epithelial
barrier lining
uroepithelium
Homo sapiens
Fetal
Muscular
striatum
skeletal
cell lineage
highly in the basal or progenitor layers of many epithelial tissues
cell lines
constitutively expressed in female germ cells during meiotic arrest
fluid/secretion
at STAGE
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)
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
