Bioinformatics Database
TP63: Tumor protein p63
Cellular Process
Enamel formation
Gene Name
TP63: Tumor protein p63
Gene ID
8626
Gene Sequence
General Description
This gene encodes a member of the p53 family of transcription factors. The functional domains of p53 family proteins include an N-terminal transactivation domain, a central DNA-binding domain and an oligomerization domain. Alternative splicing of this gene and the use of alternative promoters results in multiple transcript variants encoding different isoforms that vary in their functional properties.
Alternative titles; symbols
Tumor Protein p73-Like; TP73L p53-Related Protein p63; p63 KET
Chromosome
Chromosome 3
Cytogenetic location
3q28
Encoded Protein
Tumor protein 63 isoform 1
Function of the protein in oral and tooth development
The Tp63 gene encodes for multiple isoforms of the p63 transcription factor. The biological role of p63 involves wide-ranging effects on development, differentiation, and cellular lineage choices. The crucial function of p63 is identified by the study of p63 knockout mice, showing a profound block in the development of stratified epithelia and aplasia of multiple ectodermal appendages, as well as orofacial clefting and limb defects (Romano et al., 2012).
In another study, Kock et al, (2009) aimed to to investigate the expression of the p63 gene in normal human tooth buds at different gestational stages using immunostaining. The study showed a positive reaction of p63 in both the cap stage and the bell stage. In the early cap stage, there is a strong positive reaction to p63 in the enamel knot, suggesting that p63 may have an important regulatory function in the enamel knot (Kock et al, 2009).
Matsuura et al, (2012) investigated the role of p51/p63 in ameloblastic cell differentiation. The resutls showed that "the expression of ΔNp51B/ΔNp63α, an isoform without transactivation domain, was detected at high level in immature cells, while the expression of TAp51/TAp63 isoforms, isoforms of with the transactivation domain, was detected at high level in mature cells. Moreover, induction of TAp51A/TAp63γ expression led to down-regulation of ΔNp51B/ΔNp63α expression and cell proliferation. Interestingly, this also led to up-regulation of ameloblastin expression, a differentiation marker of amelogenesis' (Matsuura et al, 2012).
Dental and Oral Diseases
Ectrodactyly, Ectodermal Dysplasia, and Cleft Lip/Palate Syndrome 3
Orofacial Cleft 8
Ankyloblepharon-Ectodermal Defects-Clefting (AEC) Syndrome (Hay-Wells syndrome)
acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome
Limb-Mammary Syndrome
(OMIM ID: 603273)
Protein Sequence
>NP_001316893.1 tumor protein 63 isoform 13 [Homo sapiens]
MKCWEQRDWTAFTKVGKPCFVETPAHFSWKESYYRSTMSQSTQTNEFLSPEVFQHIWDFLEQPICSVQPI
DLNFVDEPSEDGATNKIEISMDCIRMQDSDLSDPMWPQYTNLGLLNSMDQQIQNGSSSTSPYNTDHAQNS
VTAPSPYAQPSSTFDALSPSPAIPSNTDYPGPHSFDVSFQQSSTAKSATWTYSTELKKLYCQIAKTCPIQ
IKVMTPPPQGAVIRAMPVYKKAEHVTEVVKRCPNHELSREFNEGQIAPPSHLIRVEGNSHAQYVEDPITG
RQSVLVPYEPPQVGTEFTTVLYNFMCNSSCVGGMNRRPILIIVTLETRDGQVLGRRCFEARICACPGRDR
KADEDSIRKQQVSDSTKNGDGTKRPFRQNTHGIQMTSIKKRRSPDDELLYLPVRGRETYEMLLKIKESLE
LMQYLPQHTIETYRQQQQQQHQHLLQKQTSIQSPSSYGNSSPPLNKMNSMNKLPSVSQLINPQQRNALTP
TTIPDGMGANIPMMGTHMPMAGDMNGLSPTQALPPPLSMPSTSHCTPPPPYPTDCSIVSFLARLGCSSCL
DYFTTQGLTTIYQIEHYSMDDLASLKIPEQFRHAIWKGILDHRQLHEFSSPSHLLRTPSSASTVSVGSSE
TRGERVIDAVRFTLRQTISFPPRDEWNDFNFDMDARRNKQQRIKEEGE
Mutations
Ectrodactyly, Ectodermal Dysplasia, and Cleft Lip/Palate Syndrome 3 (EEC3): Celli et al. (1999) identified mutations in 9 unrelated EEC3 families. Eight mutations resulted in amino acid substitutions that were predicted to abolish the DNA binding capacity of p63; the ninth was a frameshift mutation. Six of the 9 mutations were C-to-T transversions at CpG dinucleotides (Celli et al., 1999)
Orofacial Cleft 8: Arg313-to-Gly; 2-bp duplication (c.819-820dupCC).
Ankyloblepharon-Ectodermal Defects-Clefting (AEC) Syndrome (Hay-Wells syndrome): leu518-to-phe; Cys522-to-Gly
acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome: Asn6-to-His; arg298-to-gln; Val114-to-Met; Pro127-to-Leu
Limb-Mammary Syndrome: 2-BP DEL, 1576TT;
Related Literature
Celli et al., (1999): https://doi-org/10.1016/s0092-8674(00)81646-3
Romano et al., (2012): https://doi-org/10.1177/0022034511411302
Kock et al, (2005). https://doi.org/10.1080/00016350510019919
Matsuura et al., (2012). https://doi.org/10.1016/j.archoralbio.2012.02.023