CleftGeneDB-Search

Gene: Tp63

Basic information

Tag	Content
Uniprot ID	O88898; O88897; O88899; O89097; Q8C826; Q9QWY9; Q9QWZ0;
Entrez ID	22061
Genbank protein ID	BAA32432.1; AAP87985.1; AAP87984.1; AAC62641.1; AAC62642.1; AAC62639.1; AAP87982.1; AAC62640.1; BAC33397.1; AAC62643.1; AAP87983.1; AAC62644.1; AAP87986.1; AAP87987.1;
Genbank nucleotide ID	NM_001127265.1; NM_011641.2; NM_001127260.1; NM_001127262.1; NM_001127259.1; NM_001127261.1; NM_001127264.1;
Ensembl protein ID	ENSMUSP00000110965; ENSMUSP00000038117; ENSMUSP00000067005; ENSMUSP00000110963;
Ensembl nucleotide ID	ENSMUSG00000022510
Gene name	Tumor protein 63
Gene symbol	Tp63
Organism	Mus musculus
NCBI taxa ID	10090
Cleft type	CPO,CLP
Developmental stage
Data sources	Manually collected
Reference	20424327; 20424325; 10227294; 18634775; 22247000;
Functional description	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. 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. Activates transcription of the p21 promoter (By similarity). Activates RIPK4 transcription. 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.
Sequence	MNFETSRCAT LQYCPDPYIQ RFIETPAHFS WKESYYRSAM SQSTQTSEFL SPEVFQHIWD 60 FLEQPICSVQ PIELNFVDEP SENGATNKIE ISMDCIRMQD SDLSDPMWPQ YTNLGLLNSM 120 DQQIQNGSSS TSPYNTDHAQ NSVTAPSPYA QPSSTFDALS PSPAIPSNTD YPGPHSFDVS 180 FQQSSTAKSA TWTYSTELKK LYCQIAKTCP IQIKVMTPPP QGAVIRAMPV YKKAEHVTEV 240 VKRCPNHELS REFNEGQIAP PSHLIRVEGN SHAQYVEDPI TGRQSVLVPY EPPQVGTEFT 300 TVLYNFMCNS SCVGGMNRRP ILIIVTLETR DGQVLGRRCF EARICACPGR DRKADEDSIR 360 KQQVSDSAKN GDGTKRPFRQ NTHGIQMTSI KKRRSPDDEL LYLPVRGRET YEMLLKIKES 420 LELMQYLPQH TIETYRQQQQ QQHQHLLQKQ TSMQSQSSYG NSSPPLNKMN SMNKLPSVSQ 480 LINPQQRNAL TPTTMPEGMG ANIPMMGTHM PMAGDMNGLS PTQALPPPLS MPSTSHCTPP 540 PPYPTDCSIV SFLARLGCSS CLDYFTTQGL TTIYQIEHYS MDDLASLKIP EQFRHAIWKG 600 ILDHRQLHDF SSPPHLLRTP SGASTVSVGS SETRGERVID AVRFTLRQTI SFPPRDEWND 660 FNFDMDSRRN KQQRIKEEGE

Abbreviation :
CLO : cleft lip only. CPO : cleft palate only. CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.

Protein structural annotations

3D structure in PDB database

PDB ID
5N2O

Protein disorder information

Orthologous information

Relation	Gene symbol	Entrez ID	UniProt ID	Cleft type	Species	Evidence	Details
1:1 ortholog	TP63	615335	F1MKA9		Bos taurus	Prediction	More>>
1:1 ortholog	TP63		F1PL57		Canis lupus familiaris	Prediction	More>>
1:1 ortholog	TP63		A0A452FUS8		Capra hircus	Prediction	More>>
1:1 ortholog	TP63	8626	Q9H3D4		Homo sapiens	Publication	More>>
1:1 ortholog	Tp63	22061	O88898	CPO,CLP	Mus musculus	Publication	More>>
1:1 ortholog	TP63		A0A2I3RNZ6		Pan troglodytes	Prediction	More>>
1:1 ortholog	TP63		A0A480T7V4		Sus scrofa	Prediction	More>>
1:1 ortholog	TP63	100355881	G1TBP7		Oryctolagus cuniculus	Prediction	More>>
1:1 ortholog	Tp63	246334	Q9JJP6		Rattus norvegicus	Prediction	More>>
1:1 ortholog	tp63		F1QLJ1		Danio rerio	Prediction	More>>

Identified variants/mutations related to cleft phenotype

Gene symbol	Significant Variants/SNPS	Methods	PubMed ID
TP63	c.1542A>T; p.L518F	PCR; direct sequencing	11159940
TP63	c.1589G>T; p.G534V	PCR; direct sequencing	11159940
TP63	c.1564T>G; p.G526G	PCR; direct sequencing	11159940
TP63	c.1607A>T; p.Q540L	PCR; direct sequencing	11159940
TP63	c.1610T>C; p.I541T	PCR; direct sequencing	11159940
TP63	c.1540T>G; p.L518V	PCR; direct sequencing	11159940
TP63	c.1597A>C; p.T537P	PCR; direct sequencing	11159940
TP63	c.1566T>G; p.C526W	PCR; direct sequencing	11159940
TP63	c.819_820dupCC; p.Gln274fs*4	WES	29500247
TP63	c.1798G>C; p.Gly600Arg (heterozygous)	sequencing	32953416
TP63	c.1769C>T; p.P590L (heterozygous)	WES and Sanger sequencing	31050217
TP63	p.R304W (heterozygous)	WES and Sanger sequencing	30025988
TP63	rs7653848	Sanger sequencing	32687624
TP63	rs7624324	Sanger sequencing	32687624
TP63	rs6790167	Sanger sequencing	32687624
TP63	rs1345186	Sanger sequencing	32687624
TP63	rs9332461A>G	TaqMan genotyping assay	31825181
TP63	c.1324C>T; p.Q442* (heterozygous)	WES and Sanger sequencing	33622322

Other genetic variants/mutations

ID	Variant	Type	Disease	Chromosome\Coordinate	Evidence
rs32471981	p.Ile19Phe	missense variant	-	NC_000082.6:g.25684344A>T	UniProt

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO ID	GO Term	Evidence
GO:0001228	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA
GO:0002039	p53 binding	ISO
GO:0003677	DNA binding	IDA
GO:0003682	chromatin binding	ISO
GO:0003682	chromatin binding	IDA
GO:0003684	damaged DNA binding	IDA
GO:0003690	double-stranded DNA binding	ISO
GO:0003700	DNA-binding transcription factor activity	ISO
GO:0005515	protein binding	IPI
GO:0019904	protein domain specific binding	ISO
GO:0042802	identical protein binding	ISO
GO:0042802	identical protein binding	IPI
GO:0043565	sequence-specific DNA binding	IDA
GO:0044212	transcription regulatory region DNA binding	IEA
GO:0046872	metal ion binding	IEA
GO:0050699	WW domain binding	ISO
GO:0097371	MDM2/MDM4 family protein binding	ISO

GO:Biological Process

GO ID	GO Term	Evidence
GO:0000122	negative regulation of transcription by RNA polymerase II	IDA
GO:0001302	replicative cell aging	ISO
GO:0001501	skeletal system development	IMP
GO:0001736	establishment of planar polarity	IDA
GO:0001738	morphogenesis of a polarized epithelium	IMP
GO:0001942	hair follicle development	IMP
GO:0002064	epithelial cell development	IMP
GO:0006338	chromatin remodeling	IMP
GO:0006915	apoptotic process	TAS
GO:0006974	cellular response to DNA damage stimulus	ISO
GO:0007219	Notch signaling pathway	IEA
GO:0007275	multicellular organism development	TAS
GO:0007283	spermatogenesis	IEA
GO:0007389	pattern specification process	IMP
GO:0007499	ectoderm and mesoderm interaction	IMP
GO:0007569	cell aging	IMP
GO:0008283	cell population proliferation	IMP
GO:0008544	epidermis development	IMP
GO:0009887	animal organ morphogenesis	IMP
GO:0009913	epidermal cell differentiation	IMP
GO:0009954	proximal/distal pattern formation	IMP
GO:0010259	multicellular organism aging	IMP
GO:0010481	epidermal cell division	IMP
GO:0010482	regulation of epidermal cell division	IMP
GO:0010838	positive regulation of keratinocyte proliferation	IGI
GO:0030154	cell differentiation	IMP
GO:0030216	keratinocyte differentiation	IDA
GO:0030326	embryonic limb morphogenesis	IMP
GO:0030326	embryonic limb morphogenesis	IGI
GO:0030850	prostate gland development	IMP
GO:0030855	epithelial cell differentiation	IMP
GO:0030859	polarized epithelial cell differentiation	IMP
GO:0031069	hair follicle morphogenesis	IMP
GO:0033147	negative regulation of intracellular estrogen receptor signaling pathway	IMP
GO:0035115	embryonic forelimb morphogenesis	IMP
GO:0035116	embryonic hindlimb morphogenesis	IMP
GO:0036342	post-anal tail morphogenesis	IMP
GO:0042475	odontogenesis of dentin-containing tooth	IMP
GO:0042771	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IMP
GO:0043281	regulation of cysteine-type endopeptidase activity involved in apoptotic process	IMP
GO:0043589	skin morphogenesis	IMP
GO:0045617	negative regulation of keratinocyte differentiation	IMP
GO:0045669	positive regulation of osteoblast differentiation	ISO
GO:0045747	positive regulation of Notch signaling pathway	ISO
GO:0045747	positive regulation of Notch signaling pathway	IMP
GO:0045892	negative regulation of transcription, DNA-templated	ISO
GO:0045893	positive regulation of transcription, DNA-templated	ISO
GO:0045944	positive regulation of transcription by RNA polymerase II	ISO
GO:0045944	positive regulation of transcription by RNA polymerase II	IMP
GO:0045944	positive regulation of transcription by RNA polymerase II	IDA
GO:0048485	sympathetic nervous system development	IMP
GO:0048646	anatomical structure formation involved in morphogenesis	IMP
GO:0048807	female genitalia morphogenesis	IMP
GO:0051289	protein homotetramerization	ISO
GO:0051402	neuron apoptotic process	IMP
GO:0060197	cloacal septation	IMP
GO:0060513	prostatic bud formation	IMP
GO:0060529	squamous basal epithelial stem cell differentiation involved in prostate gland acinus development	IMP
GO:0061436	establishment of skin barrier	IMP
GO:0098773	skin epidermis development	IMP
GO:1902808	positive regulation of cell cycle G1/S phase transition	ISO
GO:1904674	positive regulation of somatic stem cell population maintenance	IMP
GO:1904888	cranial skeletal system development	IMP
GO:2000271	positive regulation of fibroblast apoptotic process	ISO
GO:2000381	negative regulation of mesoderm development	IMP
GO:2000773	negative regulation of cellular senescence	ISO
GO:2001235	positive regulation of apoptotic signaling pathway	IDA

GO:Cellular Component

GO ID	GO Term	Evidence
GO:0000790	nuclear chromatin	ISO
GO:0005634	nucleus	ISO
GO:0005634	nucleus	IDA
GO:0005654	nucleoplasm	ISO
GO:0005737	cytoplasm	ISO
GO:0005791	rough endoplasmic reticulum	ISO
GO:0030425	dendrite	ISO
GO:0032991	protein-containing complex	ISO
GO:0043005	neuron projection	ISO

Reactome Pathway

Reactome ID	Reactome Term	Evidence
R-MMU-212436	Generic Transcription Pathway	IEA
R-MMU-3700989	Transcriptional Regulation by TP53	IEA
R-MMU-5633007	Regulation of TP53 Activity	IEA
R-MMU-6804759	Regulation of TP53 Activity through Association with Co-factors	IEA
R-MMU-73857	RNA Polymerase II Transcription	IEA
R-MMU-74160	Gene expression (Transcription)	IEA

Drugs and compounds information

ID	Drug Name	Action	PubMed
C548651	2-(1'H-indole-3'-carbonyl)thiazole-4-carboxylic acid methyl ester	2-(1'H-indole-3'-carbonyl)thiazole-4-carboxylic acid methyl ester results in increased expression of TRP63 mRNA	19933214
C010914	2,4-diaminotoluene	2,4-diaminotoluene results in decreased expression of TRP63 mRNA	20713471
C049584	2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine results in decreased expression of TRP63 protein	22581815
C006551	2-amino-2-methyl-1-propanol	2-amino-2-methyl-1-propanol results in decreased expression of TRP63 mRNA	25088246
C012606	4-vinyl-1-cyclohexene dioxide	4-vinyl-1-cyclohexene dioxide affects the expression of TRP63 mRNA	20829426
C496492	abrine	abrine results in increased expression of TRP63 mRNA	22595364
D000082	Acetaminophen	MAP3K5 protein affects the reaction [Acetaminophen results in increased expression of TRP63 mRNA]	18700144
D001564	Benzo(a)pyrene	Benzo(a)pyrene results in decreased expression of TRP63 mRNA	21964900
D001564	Benzo(a)pyrene	Benzo(a)pyrene results in increased expression of TRP63 mRNA	23735875
C543008	bis(4-hydroxyphenyl)sulfone	bis(4-hydroxyphenyl)sulfone results in increased expression of TRP63 mRNA	30951980
C006780	bisphenol A	bisphenol A affects the methylation of TRP63 promoter	27334623
C006780	bisphenol A	bisphenol A results in increased expression of TRP63 mRNA	30951980
C000611646	bisphenol F	bisphenol F results in increased expression of TRP63 mRNA	30951980
C041517	dibenzo(a,l)pyrene	dibenzo(a,l)pyrene results in increased expression of TRP63 mRNA	25908611
D004642	Emodin	Emodin results in increased expression of TRP63 mRNA	15612046
D015946	Ethylene Dibromide	Ethylene Dibromide results in increased expression of TRP63 mRNA	15612046
C002469	fusarenon-X	fusarenon-X results in decreased expression of TRP63 mRNA	24983900
C004312	glycidol	glycidol results in increased expression of TRP63 mRNA	15612046
D006108	Graphite	Graphite results in increased expression of TRP63 mRNA	27440207
D006918	Hydroxyurea	Hydroxyurea results in decreased expression of TRP63 mRNA	29228353
D007654	Ketoconazole	Ketoconazole results in decreased expression of TRP63 mRNA	25808816
C554430	LDN 193189	LDN 193189 results in decreased expression of TRP63 protein alternative form	23243027
C008261	lead acetate	lead acetate results in increased expression of TRP63 mRNA	22609695
C004925	methylmercuric chloride	methylmercuric chloride affects the expression of TRP63 mRNA	20864626
D009151	Mustard Gas	Mustard Gas results in increased expression of TRP63 mRNA	15674844
D037742	Nanotubes, Carbon	Nanotubes, Carbon analog results in increased expression of TRP63 mRNA	25554681
D037742	Nanotubes, Carbon	Nanotubes, Carbon results in increased expression of TRP63 mRNA	25554681
D015125	Oxyquinoline	Oxyquinoline results in increased expression of TRP63 mRNA	15612046
C076994	perfluorooctane sulfonic acid	perfluorooctane sulfonic acid results in increased expression of TRP63 mRNA	22237054
D020123	Sirolimus	Sirolimus results in decreased expression of TRP63 protein	20038814
C009277	sodium arsenate	sodium arsenate results in increased expression of TRP63 mRNA	21795629; 30953684;
D013749	Tetrachlorodibenzodioxin	Tetrachlorodibenzodioxin affects the expression of TRP63 mRNA	21570461; 24058054;
D013749	Tetrachlorodibenzodioxin	Tetrachlorodibenzodioxin results in increased expression of TRP63 mRNA	17586704; 19933214;
C009495	titanium dioxide	titanium dioxide affects the expression of TRP63 mRNA	23557971
D014212	Tretinoin	Tretinoin results in decreased expression of TRP63 mRNA alternative form	16998800
C015559	trimellitic anhydride	trimellitic anhydride results in decreased expression of TRP63 mRNA	19042947
D001335	Vehicle Emissions	Vehicle Emissions results in increased methylation of TRP63 gene	25560391

Functional annotations

Keywords

Keyword ID	Keyword Term
KW-0002	3D-structure
KW-0010	Activator
KW-0877	Alternative promoter usage
KW-0025	Alternative splicing
KW-0053	Apoptosis
KW-0217	Developmental protein
KW-0238	DNA-binding
KW-1017	Isopeptide bond
KW-0479	Metal-binding
KW-0914	Notch signaling pathway
KW-0539	Nucleus
KW-1185	Reference proteome
KW-0804	Transcription
KW-0805	Transcription regulation
KW-0832	Ubl conjugation
KW-0862	Zinc

Interpro

InterPro ID	InterPro Term
IPR008967	p53-like_TF_DNA-bd
IPR012346	p53/RUNT-type_TF_DNA-bd_sf
IPR011615	p53_DNA-bd
IPR036674	p53_tetramer_sf
IPR010991	p53_tetrameristn
IPR002117	p53_tumour_suppressor
IPR001660	SAM
IPR013761	SAM/pointed_sf
IPR032645	Tp63
IPR037611	Tumor-p63_SAM

PROSITE

PROSITE ID	PROSITE Term
PS00348	P53

Pfam

Pfam ID	Pfam Term
PF00870	P53
PF07710	P53_tetramer
PF07647	SAM_2