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P10361 (P53_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 167. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cellular tumor antigen p53
Alternative name(s):
Tumor suppressor p53
Gene names
Name:Tp53
Synonyms:P53
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length391 AA.
Sequence statusComplete.
Protein existenceEvidence at protein 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 BANP. Interacts with ARMD10, E4F1, CDKN2AIP, NUAK1, UHRF2 and STK11/LKB1. Interacts with CHD8, leading to recruit histone H1 and prevent transactivation activity By similarity. Interacts with YWHAZ; the interaction enhances TP53 transcriptional activity. Phosphorylation of YWHAZ on 'Ser-58' inhibits this interaction By similarity. Interacts with HSP90AB1. 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. 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, SETD2, 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. Interacts with ZNF385A; the interaction is direct and enhances p53/TP53 transactivation functions on cell-cycle arrest target genes, resulting in growth arrest By similarity. Interacts with ANKRD2 By similarity. Interacts with RFFL (via RING-type zinc finger); involved in p53/TP53 ubiquitination By similarity. Ref.5

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. Endoplasmic reticulum By similarity. Mitochondrion matrix. Note: Interaction with BANP promotes nuclear localization. Translocates to mitochondria upon oxidative stress By similarity. Ref.6

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-390 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, 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 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-289 and Lys-290, which leads to proteasomal degradation. Deubiquitinated by USP10, leading to stabilize it. Ubiquitinated by TRIM24 and RFFL, 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. Sumoylated at Lys-384 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 processApoptosis
Cell cycle
Necrosis
Transcription
Transcription regulation
   Cellular componentCytoplasm
Endoplasmic reticulum
Mitochondrion
Nucleus
   DiseaseTumor suppressor
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
   PTMAcetylation
Isopeptide bond
Methylation
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator

Inferred from Biological aspect of Ancestor. Source: RefGenome

DNA strand renaturation

Inferred from sequence or structural similarity. Source: UniProtKB

aging

Inferred from expression pattern PubMed 18037131. Source: RGD

cell aging

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to UV

Inferred from Biological aspect of Ancestor. Source: RefGenome

cellular response to heat

Inferred from expression pattern PubMed 11295070. Source: RGD

cellular response to organonitrogen compound

Inferred from expression pattern PubMed 11502571. Source: RGD

intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

Inferred from Biological aspect of Ancestor. Source: RefGenome

mitotic G1 DNA damage checkpoint

Inferred from Biological aspect of Ancestor. Source: RefGenome

multicellular organismal development

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of DNA biosynthetic process

Inferred from mutant phenotype PubMed 11502571. Source: RGD

negative regulation of cell growth

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of smooth muscle cell proliferation

Inferred from mutant phenotype PubMed 17659301. Source: RGD

negative regulation of transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 8389468. Source: UniProtKB

nucleotide-excision repair

Inferred from sequence or structural similarity. Source: UniProtKB

oligodendrocyte apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of apoptotic process

Inferred from mutant phenotype PubMed 16688778. Source: RGD

positive regulation of cell cycle

Inferred from mutant phenotype PubMed 18026139. Source: RGD

positive regulation of histone deacetylation

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of leukocyte migration

Inferred from mutant phenotype PubMed 18317410. Source: RGD

positive regulation of neuron apoptotic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of release of cytochrome c from mitochondria

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 11278372. Source: BHF-UCL

protein tetramerization

Inferred from electronic annotation. Source: InterPro

regulation of intracellular pH

Inferred from mutant phenotype PubMed 16688778. Source: RGD

regulation of transcription from RNA polymerase II promoter

Traceable author statement PubMed 11502571. Source: RGD

response to UV

Inferred from expression pattern PubMed 17724205. Source: RGD

response to UV-B

Inferred from expression pattern PubMed 22559303. Source: RGD

response to X-ray

Inferred from expression pattern PubMed 17699727. Source: RGD

response to amino acid

Inferred from expression pattern PubMed 17542038. Source: RGD

response to caffeine

Inferred from expression pattern PubMed 16544096. Source: RGD

response to cytokine

Inferred from expression pattern PubMed 17651018. Source: RGD

response to drug

Inferred from expression pattern PubMed 18336558. Source: RGD

response to gamma radiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

response to hyperoxia

Inferred from expression pattern PubMed 18337831. Source: RGD

response to inorganic substance

Inferred from expression pattern PubMed 18335527. Source: RGD

response to metal ion

Inferred from expression pattern PubMed 17466256. Source: RGD

response to organic cyclic compound

Inferred from expression pattern PubMed 18093815. Source: RGD

response to organonitrogen compound

Inferred from expression pattern PubMed 18311796. Source: RGD

response to oxidative stress

Inferred from expression pattern PubMed 17600529. Source: RGD

response to retinoic acid

Inferred from expression pattern PubMed 17962954. Source: RGD

response to vitamin B3

Inferred from expression pattern PubMed 17516866. Source: RGD

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

wound healing

Inferred from expression pattern PubMed 18337831. Source: RGD

   Cellular_componentchromatin

Inferred from direct assay PubMed 15632413. Source: RGD

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 16282427. Source: RGD

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

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

replication fork

Inferred from Biological aspect of Ancestor. Source: RefGenome

transcription factor complex

Inferred from direct assay PubMed 15632413. Source: RGD

   Molecular_functionATP binding

Inferred from sequence or structural similarity. Source: UniProtKB

DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

chromatin binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

copper ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

damaged DNA binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

double-stranded DNA binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

p53 binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein C-terminus binding

Inferred from physical interaction PubMed 11278372. Source: RGD

protein binding

Inferred from physical interaction PubMed 12464630PubMed 8389468. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay PubMed 15632413. Source: RGD

sequence-specific DNA binding transcription factor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

transcription cofactor binding

Inferred from physical interaction PubMed 21792911. Source: RGD

transcription regulatory region DNA binding

Inferred from electronic annotation. Source: InterPro

ubiquitin protein ligase binding

Inferred from physical interaction PubMed 16330492. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 391391Cellular tumor antigen p53
PRO_0000185712

Regions

DNA binding100 – 290191 By similarity
Region1 – 4747Transcription activation (acidic)
Region64 – 10845Interaction with WWOX By similarity
Region98 – 368271Interaction with HIPK1 By similarity
Region98 – 298201Required for interaction with ZNF385A By similarity
Region111 – 234124Required for interaction with FBXO42 By similarity
Region114 – 290177Interaction with AXIN1 By similarity
Region254 – 29239Interaction with E4F1 By similarity
Region271 – 2788Interaction with DNA By similarity
Region317 – 35842Interaction with HIPK2 By similarity
Region323 – 35432Oligomerization
Region357 – 3615Interaction with USP7 By similarity
Region366 – 38520Basic (repression of DNA-binding)
Motif303 – 31917Bipartite nuclear localization signal By similarity
Motif337 – 34812Nuclear export signal By similarity
Motif368 – 3703[KR]-[STA]-K motif

Sites

Metal binding1741Zinc By similarity
Metal binding1771Zinc By similarity
Metal binding2361Zinc By similarity
Metal binding2401Zinc By similarity
Site1181Interaction with DNA By similarity

Amino acid modifications

Modified residue91Phosphoserine; by HIPK4 By similarity
Modified residue151Phosphoserine; by CDK5, PRPK, AMPK, NUAK1 and ATM By similarity
Modified residue181Phosphothreonine; by CK1, VRK1 and VRK2 By similarity
Modified residue201Phosphoserine; by CHEK2, CK1 and PLK3 By similarity
Modified residue391Phosphoserine; by MAPKAPK5 By similarity
Modified residue1181N6-acetyllysine; by KAT6A By similarity
Modified residue1811Phosphoserine; by AURKB By similarity
Modified residue2671Phosphoserine; by AURKB By similarity
Modified residue2821Phosphothreonine; by AURKB By similarity
Modified residue3031N6-acetyllysine By similarity
Modified residue3131Phosphoserine; by AURKA, CDK1 and CDK2 By similarity
Modified residue3191N6-acetyllysine By similarity
Modified residue3681N6,N6-dimethyllysine; alternate By similarity
Modified residue3681N6-methyllysine; by SMYD2; alternate By similarity
Modified residue3701N6-methyllysine; by SETD7 By similarity
Modified residue3711N6,N6-dimethyllysine; by EHMT1 and EHMT2; alternate By similarity
Modified residue3711N6-acetyllysine; alternate By similarity
Modified residue3791N6-acetyllysine By similarity
Modified residue3801N6,N6-dimethyllysine; alternate By similarity
Modified residue3801N6-acetyllysine; by KAT6A; alternate By similarity
Modified residue3801N6-methyllysine; by SETD8; alternate By similarity
Modified residue3901Phosphoserine; by CK2, CDK2 and NUAK1 By similarity
Cross-link289Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link290Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link384Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Natural variations

Natural variant1031G → S.
Natural variant2561E → G.

Experimental info

Sequence conflict1741C → W in AAA41788. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P10361 [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: E62522313A5C872F

FASTA39143,451
        10         20         30         40         50         60 
MEDSQSDMSI ELPLSQETFS CLWKLLPPDD ILPTTATGSP NSMEDLFLPQ DVAELLEGPE 

        70         80         90        100        110        120 
EALQVSAPAA QEPGTEAPAP VAPASATPWP LSSSVPSQKT YQGNYGFHLG FLQSGTAKSV 

       130        140        150        160        170        180 
MCTYSISLNK LFCQLAKTCP VQLWVTSTPP PGTRVRAMAI YKKSQHMTEV VRRCPHHERC 

       190        200        210        220        230        240 
SDGDGLAPPQ HLIRVEGNPY AEYLDDRQTF RHSVVVPYEP PEVGSDYTTI HYKYMCNSSC 

       250        260        270        280        290        300 
MGGMNRRPIL TIITLEDSSG NLLGRDSFEV RVCACPGRDR RTEEENFRKK EEHCPELPPG 

       310        320        330        340        350        360 
SAKRALPTST SSSPQQKKKP LDGEYFTLKI RGRERFEMFR ELNEALELKD ARAAEESGDS 

       370        380        390 
RAHSSYPKTK KGQSTSRHKK PMIKKVGPDS D 

« Hide

References

« Hide 'large scale' references
[1]"Nucleotide sequence of a cDNA encoding the rat p53 nuclear oncoprotein."
Soussi T.
Nucleic Acids Res. 16:11384-11384(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Structure of the rat p53 tumor suppressor gene."
Hulla J.E., Schneider R.P.
Nucleic Acids Res. 21:713-717(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Glucose catabolism in cancer cells. The type II hexokinase promoter contains functionally active response elements for the tumor suppressor p53."
Mathupala S.P., Heese C., Pedersen P.L.
J. Biol. Chem. 272:22776-22780(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Heart and Thymus.
[5]"Heat shock protein 84 forms a complex with mutant p53 protein predominantly within a cytoplasmic compartment of the cell."
Sepehrnia B., Paz I.B., Dasgupta G., Momand J.
J. Biol. Chem. 271:15084-15090(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HSP90AB1.
Tissue: Embryo.
[6]"p53 opens the mitochondrial permeability transition pore to trigger necrosis."
Vaseva A.V., Marchenko N.D., Ji K., Tsirka S.E., Holzmann S., Moll U.M.
Cell 149:1536-1548(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X13058 mRNA. Translation: CAA31457.1.
L07910 expand/collapse EMBL AC list , L07904, L07905, L07906, L07907, L07908, L07909 Genomic DNA. Translation: AAA41788.1.
U90328 mRNA. Translation: AAB80959.1.
BC081788 mRNA. Translation: AAH81788.2.
BC098663 mRNA. Translation: AAH98663.1.
PIRS02192.
RefSeqNP_112251.2. NM_030989.3.
XP_006246656.1. XM_006246594.1.
XP_006246657.1. XM_006246595.1.
UniGeneRn.54443.

3D structure databases

ProteinModelPortalP10361.
SMRP10361. Positions 93-288, 317-358.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid246960. 9 interactions.
DIPDIP-46016N.
IntActP10361. 4 interactions.
MINTMINT-4651801.
STRING10116.ENSRNOP00000047840.

PTM databases

PhosphoSiteP10361.

Proteomic databases

PaxDbP10361.
PRIDEP10361.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000046490; ENSRNOP00000047840; ENSRNOG00000010756.
GeneID24842.
KEGGrno:24842.
UCSCRGD:3889. rat.

Organism-specific databases

CTD7157.
RGD3889. Tp53.

Phylogenomic databases

eggNOGNOG80479.
GeneTreeENSGT00390000015092.
HOGENOMHOG000039957.
HOVERGENHBG005201.
InParanoidP10361.
KOK04451.
OMAVVSTRIC.
OrthoDBEOG7JQBNW.
PhylomeDBP10361.
TreeFamTF106101.

Gene expression databases

ArrayExpressP10361.
GenevestigatorP10361.

Family and domain databases

Gene3D2.60.40.720. 1 hit.
4.10.170.10. 1 hit.
InterProIPR008967. 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]
PANTHERPTHR11447. PTHR11447. 1 hit.
PfamPF00870. P53. 1 hit.
PF08563. P53_TAD. 1 hit.
PF07710. P53_tetramer. 1 hit.
[Graphical view]
PRINTSPR00386. P53SUPPRESSR.
SUPFAMSSF47719. SSF47719. 1 hit.
SSF49417. SSF49417. 1 hit.
PROSITEPS00348. P53. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio604596.
PROP10361.

Entry information

Entry nameP53_RAT
AccessionPrimary (citable) accession number: P10361
Secondary accession number(s): O09168, Q4KMA9, Q66HM0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: June 11, 2014
This is version 167 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families