P13481 (P53_CHLAE) 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

Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops)

Taxonomic identifier

9534 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Cercopithecoidea › Cercopithecidae › Cercopithecinae › Chlorocebus

Protein attributes

Sequence length	393 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; the 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-382) with L3MBTL1. Interacts with GRK5. 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 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. Interacts with UBC9 By similarity. Forms a complex with UBC9 and PRKRA By similarity. Interacts with ZNF385B; the interaction is direct 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. Phosphorylated on Thr-55 by TAF1 which promotes MDM2-mediated TP53 degradation. Phosphorylated on Ser-33 by CDK7 in a CAK complex in response to DNA damage. Phosphorylated by HIPK1. Phosphorylated on Ser-46 by HIPK2 upon UV irradiation. Phosphorylation on Ser-46 is required for acetylation by CREBBP. Phosphorylated on Ser-392 following UV but not gamma irradiation. 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, Ser-33 and Ser-46, leading to accumulation of p53/TP53, particularly in the nucleus, thus inducing the transactivation of p53/TP53 target genes. Phosphorylated by DYRK2 at Ser-46 in response to genotoxic stress. Phosphorylated at Ser-315 and Ser-392 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 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-291 and Lys-292, 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-372 by SETD7, leading to stabilization and increased transcriptional activation. Monomethylated at Lys-370 by SMYD2, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity. Lys-372 monomethylation prevents interaction with SMYD2 and subsequent monomethylation at Lys-370. Dimethylated at Lys-373 by EHMT1 and EHMT2. Monomethylated at Lys-382 by SETD8, promoting interaction with L3MBTL1 and leading to repress transcriptional activity. Demethylation of dimethylated Lys-370 by KDM1A prevents interaction with TP53BP1 and represses TP53-mediated transcriptional activation By similarity. Sumoylated with SUMO1. Sumoylated at Lys-386 by UBC9 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
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 – 393	393	Cellular tumor antigen p53		PRO_0000185697
Regions
	DNA binding	102 – 292	191	By similarity
	Region	1 – 83	83	Interaction with HRMT1L2 By similarity
	Region	1 – 44	44	Transcription activation (acidic)
	Region	66 – 110	45	Interaction with WWOX By similarity
	Region	100 – 370	271	Interaction with HIPK1 By similarity
	Region	113 – 236	124	Required for interaction with FBXO42 By similarity
	Region	116 – 292	177	Interaction with AXIN1 By similarity
	Region	256 – 294	39	Interaction with E4F1 By similarity
	Region	273 – 280	8	Interaction with DNA By similarity
	Region	300 – 393	94	Interaction with CARM1 By similarity
	Region	319 – 360	42	Interaction with HIPK2 By similarity
	Region	325 – 356	32	Oligomerization
	Region	359 – 363	5	Interaction with USP7 By similarity
	Region	368 – 387	20	Basic (repression of DNA-binding)
	Motif	305 – 321	17	Bipartite nuclear localization signal By similarity
	Motif	339 – 350	12	Nuclear export signal By similarity
	Motif	370 – 372	3	[KR]-[STA]-K motif
Sites
	Metal binding	176	1	Zinc By similarity
	Metal binding	179	1	Zinc By similarity
	Metal binding	238	1	Zinc By similarity
	Metal binding	242	1	Zinc By similarity
	Site	120	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	33	1	Phosphoserine; by CDK5 and CDK7 By similarity
	Modified residue	37	1	Phosphoserine; by MAPKAPK5 By similarity
	Modified residue	46	1	Phosphoserine; by CDK5, DYRK2, HIPK2 and PKC/PRKCG By similarity
	Modified residue	55	1	Phosphothreonine; by TAF1 and GRK5; alternate By similarity
	Modified residue	55	1	Phosphothreonine; by TAF1; alternate By similarity
	Modified residue	120	1	N6-acetyllysine; by KAT6A By similarity
	Modified residue	183	1	Phosphoserine; by AURKB By similarity
	Modified residue	269	1	Phosphoserine; by AURKB By similarity
	Modified residue	284	1	Phosphothreonine; by AURKB By similarity
	Modified residue	305	1	N6-acetyllysine By similarity
	Modified residue	315	1	Phosphoserine; by AURKA, CDK1 and CDK2 By similarity
	Modified residue	370	1	N6,N6-dimethyllysine; alternate By similarity
	Modified residue	370	1	N6-methyllysine; by SMYD2; alternate By similarity
	Modified residue	372	1	N6-methyllysine; by SETD7 By similarity
	Modified residue	373	1	N6,N6-dimethyllysine; by EHMT1 and EHMT2; alternate By similarity
	Modified residue	373	1	N6-acetyllysine; alternate By similarity
	Modified residue	381	1	N6-acetyllysine By similarity
	Modified residue	382	1	N6,N6-dimethyllysine; alternate By similarity
	Modified residue	382	1	N6-acetyllysine; by KAT6A; alternate By similarity
	Modified residue	382	1	N6-methyllysine; by SETD8; alternate By similarity
	Modified residue	392	1	Phosphoserine; by CK2, CDK2 and NUAK1 By similarity
	Cross-link	291		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
	Cross-link	292		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
	Cross-link	386		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Sequences

	Sequence		Length	Mass (Da)
	P13481 [UniParc]. Last modified January 1, 1990. Version 1. Checksum: 9ED285C9A7855D6E	FASTA	393	43,696
	10 20 30 40 50 60 MEEPQSDPSI EPPLSQETFS DLWKLLPENN VLSPLPSQAV DDLMLSPDDL AQWLTEDPGP 70 80 90 100 110 120 DEAPRMSEAA PHMAPTPAAP TPAAPAPAPS WPLSSSVPSQ KTYHGSYGFR LGFLHSGTAK 130 140 150 160 170 180 SVTCTYSPDL NKMFCQLAKT CPVQLWVDST PPPGSRVRAM AIYKQSQHMT EVVRRCPHHE 190 200 210 220 230 240 RCSDSDGLAP PQHLIRVEGN LRVEYSDDRN TFRHSVVVPY EPPEVGSDCT TIHYNYMCNS 250 260 270 280 290 300 SCMGGMNRRP ILTIITLEDS SGNLLGRNSF EVRVCACPGR DRRTEEENFR KKGEPCHELP 310 320 330 340 350 360 PGSTKRALPN NTSSSPQPKK KPLDGEYFTL QIRGRERFEM FRELNEALEL KDAQAGKEPA 370 380 390 GSRAHSSHLK SKKGQSTSRH KKFMFKTEGP DSD

References

[1]	"Nucleotide sequence of a cDNA encoding the monkey cellular phosphoprotein p53." Rigaudy P., Eckhardt W. Nucleic Acids Res. 17:8375-8375(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X16384 mRNA. Translation: CAA34420.1.
PIR	S06594.
3D structure databases
ProteinModelPortal	P13481.
SMR	P13481. Positions 94-297, 325-356.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Phylogenomic databases
HOVERGEN	HBG005201.
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_CHLAE

Accession

Primary (citable) accession number: P13481

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 1, 1990
Last modified:	May 29, 2013
This is version 137 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program