Q95330 (P53_RABIT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cellular tumor antigen p53

Alternative name(s):
Tumor suppressor p53

Gene names

Name:

TP53

Organism

Oryctolagus cuniculus (Rabbit) [Reference proteome]

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length	391 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; te function is largely independent of transcription. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seem to have to effect on cell-cycle regulation By similarity.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subunit structure	Binds DNA as a homotetramer. Found in a complex with CABLES1 and TP73. Interacts with histone acetyltransferases EP300 and methyltransferases HRMT1L2 and CARM1, and recruits them to promoters. The C-terminus interacts with TAF1, when TAF1 is part of the TFIID complex. Interacts with HIPK1, HIPK2, AXIN1, and TP53INP1. Part of a complex consisting of TP53, HIPK2 and AXIN1. Interacts with WWOX. Interacts with USP7 and SYVN1. Interacts with HSP90AB1. Interacts with ARMD10, BANP, CDKN2AIP, NUAK1, STK11/LKB1, UHRF2 and E4F1. Interacts with CHD8, leading to recruit histone H1 and prevent transactivation activity. Interacts with YWHAZ; the interaction enhances TP53 transcriptional activity. Phosphorylation of YWHAZ on 'Ser-58' inhibits this interaction. Directly interacts with FBXO42; leading to ubiquitination and degradation of TP53. Interacts with AURKA, DAXX, BRD7 and TRIM24. Interacts (when monomethylated at Lys-380) with L3MBTL1. Binds to the CAK complex (CDK7, cyclin H and MAT1) in response to DNA damage. Interacts with CDK5 in neurons. Interacts with AURKB, UHRF2 and NOC2L. Interacts (via N-terminus) with PTK2/FAK1; this promotes ubiquitination by MDM2. Interacts with PTK2B/PYK2; this promotes ubiquitination by MDM2. Interacts with PRKCG. Interacts with GRK5. Interacts with PPIF; the association implicates preferentially tetrameric TP53, is induced by oxidative stress and is impaired by cyclosporin A (CsA). Interacts with SNAI1; the interaction induces SNAI1 degradation via MDM2-mediated ubiquitination and inhibits SNAI1-induced cell invasion By similarity. Interacts with KAT6A By similarity.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Endoplasmic reticulum By similarity. Mitochondrion matrix By similarity. Note: Interaction with BANP promotes nuclear localization. Translocates to mitochondria upon oxidative stress By similarity.
Domain	The [KR]-[STA]-K motif is specifically recognized by the SETD7 methyltransferase By similarity.
Post-translational modification	Phosphorylation on Ser residues mediates transcriptional activation. Phosphorylation at Ser-9 by HIPK4 increases repression activity on BIRC5 promoter By similarity. Phosphorylated on Thr-18 by VRK1, which may prevent the interaction with MDM2. Phosphorylated on Ser-20 by CHEK2 in response to DNA damage, which prevents ubiquitination by MDM2. Phosphorylated on Ser-20 by PLK3 in response to reactive oxygen species (ROS), promoting p53/TP53-mediated apoptosis. Probably phosphorylated on by CDK7 in a CAK complex in response to DNA damage. Phosphorylated by HIPK1. Phosphorylated on Ser-15 upon ultraviolet irradiation; which is enhanced by interaction with BANP. Stabilized by CDK5-mediated phosphorylation in response to genotoxic and oxidative stresses at Ser-15, leading to accumulation of p53/TP53, particularly in the nucleus, thus inducing the transactivation of p53/TP53 target genes. Phosphorylated at Ser-313 and Ser-390 by CDK2 in response to DNA-damage By similarity. Acetylated. Its deacetylation by SIRT1 impairs its ability to induce proapoptotic program and modulate cell senescence. Phosphorylated on Ser-390 following UV but not gamma irradiation By similarity. Ubiquitinated by MDM2 and SYVN1, which leads to proteasomal degradation. Ubiquitinated by RFWD3, which works in cooperation with MDM2 and may catalyze the formation of short polyubiquitin chains on p53/TP53 that are not targeted to the proteasome. Ubiquitinated by MKRN1 at Lys-288 and Lys-289, which leads to proteasomal degradation. Deubiquitinated by USP10, leading to stabilize it. Ubiquitinated by TRIM24, which leads to proteasomal degradation. Ubiquitination by TOPORS induces degradation. Deubiquitination by USP7, leading to stabilize it By similarity. Monomethylated at Lys-370 by SETD7, leading to stabilization and increased transcriptional activation. Monomethylated at Lys-368 by SMYD2, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity. Lys-370 monomethylation prevents interaction with SMYD2 and subsequent monomethylation at Lys-368. Dimethylated at Lys-371 by EHMT1 and EHMT2. Monomethylated at Lys-380 by SETD8, promoting interaction with L3MBTL1 and leading to repress transcriptional activity. Demethylation of dimethylated Lys-368 by KDM1A prevents interaction with TP53BP1 and represses TP53-mediated transcriptional activation By similarity. Sumoylated with SUMO1 By similarity.
Involvement in disease	p53 is found in increased amounts in a wide variety of transformed cells. p53 is frequently mutated or inactivated in many types of cancer.
Sequence similarities	Belongs to the p53 family.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle Necrosis Transcription Transcription regulation
Cellular component	Cytoplasm Endoplasmic reticulum Mitochondrion Nucleus
Disease	Tumor suppressor
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator
PTM	Acetylation Isopeptide bond Methylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA strand renaturation Inferred from sequence or structural similarity. Source: UniProtKB apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB cell aging Inferred from sequence or structural similarity. Source: UniProtKB cell cycle Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell growth Inferred from sequence or structural similarity. Source: UniProtKB nucleotide-excision repair Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of release of cytochrome c from mitochondria Inferred from sequence or structural similarity. Source: UniProtKB protein tetramerization Inferred from electronic annotation. Source: InterPro transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrial matrix Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from sequence or structural similarity. Source: UniProtKB nucleolus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from sequence or structural similarity. Source: UniProtKB DNA binding Inferred from sequence or structural similarity. Source: UniProtKB copper ion binding Inferred from sequence or structural similarity. Source: UniProtKB sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro transcription regulatory region DNA binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 391	391	Cellular tumor antigen p53		PRO_0000185711
Regions
	DNA binding	99 – 289	191	By similarity
	Region	1 – 43	43	Transcription activation (acidic)
	Region	63 – 107	45	Interaction with WWOX By similarity
	Region	97 – 368	272	Interaction with HIPK1 By similarity
	Region	110 – 233	124	Required for interaction with FBXO42 By similarity
	Region	113 – 289	177	Interaction with AXIN1 By similarity
	Region	253 – 291	39	Interaction with E4F1 By similarity
	Region	270 – 277	8	Interaction with DNA By similarity
	Region	317 – 358	42	Interaction with HIPK2 By similarity
	Region	323 – 354	32	Oligomerization
	Region	357 – 361	5	Interaction with USP7 By similarity
	Region	366 – 385	20	Basic (repression of DNA-binding)
	Motif	302 – 319	18	Bipartite nuclear localization signal By similarity
	Motif	337 – 348	12	Nuclear export signal By similarity
	Motif	368 – 370	3	[KR]-[STA]-K motif
Sites
	Metal binding	173	1	Zinc By similarity
	Metal binding	176	1	Zinc By similarity
	Metal binding	235	1	Zinc By similarity
	Metal binding	239	1	Zinc By similarity
	Site	117	1	Interaction with DNA By similarity
Amino acid modifications
	Modified residue	9	1	Phosphoserine; by HIPK4 By similarity
	Modified residue	15	1	Phosphoserine; by CDK5, PRPK, AMPK, NUAK1 and ATM By similarity
	Modified residue	18	1	Phosphothreonine; by CK1, VRK1 and VRK2 By similarity
	Modified residue	20	1	Phosphoserine; by CHEK2, CK1 and PLK3 By similarity
	Modified residue	117	1	N6-acetyllysine; by KAT6A By similarity
	Modified residue	180	1	Phosphoserine; by AURKB By similarity
	Modified residue	266	1	Phosphoserine; by AURKB By similarity
	Modified residue	281	1	Phosphothreonine; by AURKB By similarity
	Modified residue	302	1	N6-acetyllysine By similarity
	Modified residue	313	1	Phosphoserine; by AURKA, CDK1 and CDK2 By similarity
	Modified residue	368	1	N6,N6-dimethyllysine; alternate By similarity
	Modified residue	368	1	N6-methyllysine; by SMYD2; alternate By similarity
	Modified residue	370	1	N6-methyllysine; by SETD7 By similarity
	Modified residue	371	1	N6,N6-dimethyllysine; by EHMT1 and EHMT2; alternate By similarity
	Modified residue	371	1	N6-acetyllysine; alternate By similarity
	Modified residue	379	1	N6-acetyllysine By similarity
	Modified residue	380	1	N6,N6-dimethyllysine; alternate By similarity
	Modified residue	380	1	N6-acetyllysine; by KAT6A; alternate By similarity
	Modified residue	380	1	N6-methyllysine; by SETD8; alternate By similarity
	Modified residue	390	1	Phosphoserine; by CK2, CDK2 and NUAK1 By similarity
	Cross-link	288		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
	Cross-link	289		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
	Cross-link	384		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q95330 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: 86BD5B8D0B726525	FASTA	391	43,435
	10 20 30 40 50 60 MEESQSDLSL EPPLSQETFS DLWKLLPENN LLTTSLNPPV DDLLSAEDVA NWLNEDPEEG 70 80 90 100 110 120 LRVPAAPAPE APAPAAPALA APAPATSWPL SSSVPSQKTY HGNYGFRLGF LHSGTAKSVT 130 140 150 160 170 180 CTYSPCLNKL FCQLAKTCPV QLWVDSTPPP GTRVRAMAIY KKSQHMTEVV RRCPHHERCS 190 200 210 220 230 240 DSDGLAPPQH LIRVEGNLRA EYLDDRNTFR HSVVVPYEPP EVGSDCTTIH YNYMCNSSCM 250 260 270 280 290 300 GGMNRRPILT IITLEDSSGN LLGRNSFEVR VCACPGRDRR TEEENFRKKG EPCPELPPGS 310 320 330 340 350 360 SKRALPTTTT DSSPQTKKKP LDGEYFILKI RGRERFEMFR ELNEALELKD AQAEKEPGGS 370 380 390 RAHSSYLKAK KGQSTSRHKK PMFKREGPDS D

References

[1]	"cDNA cloning and immunological characterization of rabbit p53." le Goas F., May P., Ronco P., Caron de Fromentel C. Gene 185:169-173(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: New Zealand.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X90592 mRNA. Translation: CAA62216.1.
PIR	JC6193.
RefSeq	NP_001075873.1. NM_001082404.1.
UniGene	Ocu.1779.
3D structure databases
ProteinModelPortal	Q95330.
SMR	Q95330. Positions 91-292, 317-358.
ModBase	Search...
Protein-protein interaction databases
STRING	9986.ENSOCUP00000000989.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	100009292.
Organism-specific databases
CTD	7157.
Phylogenomic databases
eggNOG	NOG80479.
HOGENOM	HOG000039957.
HOVERGEN	HBG005201.
OrthoDB	EOG45757H.
Family and domain databases
Gene3D	2.60.40.720. 1 hit. 4.10.170.10. 1 hit.
InterPro	IPR008967. p53-like_TF_DNA-bd. IPR012346. p53/RUNT-type_TF_DNA-bd. IPR011615. p53_DNA-bd. IPR010991. p53_tetrameristn. IPR013872. p53_transactivation_domain. IPR002117. p53_tumour_suppressor. [Graphical view]
PANTHER	PTHR11447. PTHR11447. 1 hit.
Pfam	PF00870. P53. 1 hit. PF08563. P53_TAD. 1 hit. PF07710. P53_tetramer. 1 hit. [Graphical view]
PRINTS	PR00386. P53SUPPRESSR.
SUPFAM	SSF49417. P53_like_DNA_bnd. 1 hit. SSF47719. p53_tetrameristn. 1 hit.
PROSITE	PS00348. P53. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

P53_RABIT

Accession

Primary (citable) accession number: Q95330

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	February 1, 1997
Last modified:	May 1, 2013
This is version 128 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program