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Protein

Cellular tumor antigen p53

Gene

Tp53

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2.By similarity

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi174ZincBy similarity1
Metal bindingi177ZincBy similarity1
Metal bindingi236ZincBy similarity1
Metal bindingi240ZincBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi100 – 290By similarityAdd BLAST191

GO - Molecular functioni

GO - Biological processi

  • aging Source: RGD
  • cell aging Source: UniProtKB
  • cellular response to heat Source: RGD
  • cellular response to organonitrogen compound Source: RGD
  • cellular response to reactive oxygen species Source: RGD
  • cellular response to UV Source: GO_Central
  • circadian behavior Source: UniProtKB
  • DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator Source: GO_Central
  • DNA strand renaturation Source: UniProtKB
  • entrainment of circadian clock by photoperiod Source: UniProtKB
  • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: GO_Central
  • mitotic G1 DNA damage checkpoint Source: GO_Central
  • multicellular organism development Source: UniProtKB
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of DNA biosynthetic process Source: RGD
  • negative regulation of smooth muscle cell proliferation Source: RGD
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: GO_Central
  • nucleotide-excision repair Source: UniProtKB
  • oligodendrocyte apoptotic process Source: UniProtKB
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of cell cycle Source: RGD
  • positive regulation of histone deacetylation Source: GO_Central
  • positive regulation of leukocyte migration Source: RGD
  • positive regulation of neuron apoptotic process Source: GO_Central
  • positive regulation of release of cytochrome c from mitochondria Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • protein tetramerization Source: InterPro
  • regulation of hydrogen peroxide-induced cell death Source: UniProtKB
  • regulation of intracellular pH Source: RGD
  • regulation of transcription from RNA polymerase II promoter Source: RGD
  • response to amino acid Source: RGD
  • response to caffeine Source: RGD
  • response to cytokine Source: RGD
  • response to drug Source: RGD
  • response to ethanol Source: RGD
  • response to gamma radiation Source: GO_Central
  • response to hyperoxia Source: RGD
  • response to inorganic substance Source: RGD
  • response to metal ion Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to organonitrogen compound Source: RGD
  • response to oxidative stress Source: RGD
  • response to retinoic acid Source: RGD
  • response to UV Source: RGD
  • response to UV-B Source: RGD
  • response to vitamin B3 Source: RGD
  • response to X-ray Source: RGD
  • transcription, DNA-templated Source: UniProtKB-KW
  • wound healing Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Apoptosis, Biological rhythms, Cell cycle, Necrosis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Cellular tumor antigen p53
Alternative name(s):
Tumor suppressor p53
Gene namesi
Name:Tp53
Synonyms:P53
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi3889. Tp53.

Subcellular locationi

GO - Cellular componenti

  • chromatin Source: RGD
  • cytoplasm Source: UniProtKB
  • cytosol Source: RGD
  • endoplasmic reticulum Source: UniProtKB-SubCell
  • mitochondrial matrix Source: UniProtKB-SubCell
  • mitochondrion Source: UniProtKB
  • nucleolus Source: UniProtKB
  • nucleus Source: UniProtKB
  • replication fork Source: GO_Central
  • transcription factor complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Mitochondrion, Nucleus

Pathology & Biotechi

Involvement in diseasei

p53 is found in increased amounts in a wide variety of transformed cells. p53 is frequently mutated or inactivated in many types of cancer.

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001857121 – 391Cellular tumor antigen p53Add BLAST391

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei9Phosphoserine; by HIPK4By similarity1
Modified residuei15Phosphoserine; by CDK5, PRPK, AMPK, NUAK1 and ATMBy similarity1
Modified residuei18Phosphothreonine; by CK1, VRK1 and VRK2By similarity1
Modified residuei20Phosphoserine; by CHEK2, CK1 and PLK3By similarity1
Modified residuei39Phosphoserine; by MAPKAPK5By similarity1
Modified residuei118N6-acetyllysine; by KAT6ABy similarity1
Modified residuei181Phosphoserine; by AURKBBy similarity1
Modified residuei267Phosphoserine; by AURKBBy similarity1
Modified residuei282Phosphothreonine; by AURKBBy similarity1
Cross-linki289Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki290Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei303N6-acetyllysineBy similarity1
Modified residuei313Phosphoserine; by AURKA, CDK1 and CDK2By similarity1
Modified residuei319N6-acetyllysineBy similarity1
Modified residuei368N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei368N6-methyllysine; by SMYD2; alternateBy similarity1
Modified residuei370N6-methyllysine; by SETD7By similarity1
Modified residuei371N6,N6-dimethyllysine; by EHMT1 and EHMT2; alternateBy similarity1
Modified residuei371N6-acetyllysine; alternateBy similarity1
Modified residuei379N6-acetyllysineBy similarity1
Modified residuei380N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei380N6-acetyllysine; by KAT6A; alternateBy similarity1
Modified residuei380N6-methyllysine; by KMT5A; alternateBy similarity1
Cross-linki384Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei390Phosphoserine; by CK2, CDK2 and NUAK1By similarity1

Post-translational modificationi

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).By similarity
Acetylated. Its deacetylation by SIRT1 impairs its ability to induce proapoptotic program and modulate cell senescence. Deacetylation by SIRT2 impairs its ability to induce transcription activation in a AKT-dependent manner (By similarity).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, RFFL and RNF34, which leads to proteasomal degradation. Ubiquitination by TOPORS induces degradation. Deubiquitination by USP7, leading to stabilize it. Ubiquitinated by RFWD2, which leads to proteasomal degradation. Ubiquitination and subsequent proteasomal degradation is negatively regulated by CCAR2 (By similarity).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 KMT5A, 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).By similarity
Sumoylated with SUMO1. Sumoylated at Lys-384 by UBC9 (By similarity).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP10361.
PRIDEiP10361.

PTM databases

iPTMnetiP10361.
PhosphoSitePlusiP10361.

Expressioni

Gene expression databases

BgeeiENSRNOG00000010756.
ExpressionAtlasiP10361. baseline and differential.
GenevisibleiP10361. RN.

Interactioni

Subunit structurei

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. Interacts with YWHAZ; the interaction enhances TP53 transcriptional activity. Phosphorylation of YWHAZ on 'Ser-58' inhibits this interaction. 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. Interacts with KAT6A. Interacts with UBC9. Forms a complex with UBC9 and PRKRA. Interacts with ZNF385B; the interaction is direct. Interacts with ZNF385A; the interaction is direct and enhances p53/TP53 transactivation functions on cell-cycle arrest target genes, resulting in growth arrest. Interacts with ANKRD2. Interacts with RFFL and RNF34; involved in p53/TP53 ubiquitination. Interacts with MTA1 and RFWD2. Interacts with CCAR2 (via N-terminus). Interacts with MORC3.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei118Interaction with DNABy similarity1

GO - Molecular functioni

  • MDM2/MDM4 family protein binding Source: RGD
  • p53 binding Source: GO_Central
  • protein C-terminus binding Source: RGD
  • transcription cofactor binding Source: RGD
  • ubiquitin protein ligase binding Source: RGD

Protein-protein interaction databases

BioGridi246960. 9 interactors.
DIPiDIP-46016N.
IntActiP10361. 4 interactors.
MINTiMINT-4651801.
STRINGi10116.ENSRNOP00000047840.

Structurei

3D structure databases

ProteinModelPortaliP10361.
SMRiP10361.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 318Interaction with CCAR2By similarityAdd BLAST318
Regioni1 – 47Transcription activation (acidic)Add BLAST47
Regioni64 – 108Interaction with WWOXBy similarityAdd BLAST45
Regioni98 – 368Interaction with HIPK1By similarityAdd BLAST271
Regioni98 – 298Required for interaction with ZNF385ABy similarityAdd BLAST201
Regioni111 – 234Required for interaction with FBXO42By similarityAdd BLAST124
Regioni114 – 290Interaction with AXIN1By similarityAdd BLAST177
Regioni254 – 292Interaction with E4F1By similarityAdd BLAST39
Regioni271 – 278Interaction with DNABy similarity8
Regioni317 – 358Interaction with HIPK2By similarityAdd BLAST42
Regioni323 – 354OligomerizationAdd BLAST32
Regioni357 – 361Interaction with USP7By similarity5
Regioni366 – 385Basic (repression of DNA-binding)Add BLAST20

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi303 – 319Bipartite nuclear localization signalBy similarityAdd BLAST17
Motifi337 – 348Nuclear export signalBy similarityAdd BLAST12
Motifi368 – 370[KR]-[STA]-K motif3

Domaini

The [KR]-[STA]-K motif is specifically recognized by the SETD7 methyltransferase.By similarity

Sequence similaritiesi

Belongs to the p53 family.Curated

Phylogenomic databases

eggNOGiENOG410IITK. Eukaryota.
ENOG410ZSWV. LUCA.
GeneTreeiENSGT00390000015092.
HOGENOMiHOG000039957.
HOVERGENiHBG005201.
InParanoidiP10361.
KOiK04451.
OMAiVVSTRIC.
PhylomeDBiP10361.
TreeFamiTF106101.

Family and domain databases

CDDicd08367. P53. 1 hit.
Gene3Di2.60.40.720. 1 hit.
4.10.170.10. 1 hit.
InterProiIPR008967. 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]
PANTHERiPTHR11447. PTHR11447. 1 hit.
PfamiPF00870. P53. 1 hit.
PF08563. P53_TAD. 1 hit.
PF07710. P53_tetramer. 1 hit.
[Graphical view]
PRINTSiPR00386. P53SUPPRESSR.
SUPFAMiSSF47719. SSF47719. 1 hit.
SSF49417. SSF49417. 1 hit.
PROSITEiPS00348. P53. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P10361-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEDSQSDMSI ELPLSQETFS CLWKLLPPDD ILPTTATGSP NSMEDLFLPQ
60 70 80 90 100
DVAELLEGPE EALQVSAPAA QEPGTEAPAP VAPASATPWP LSSSVPSQKT
110 120 130 140 150
YQGNYGFHLG FLQSGTAKSV MCTYSISLNK LFCQLAKTCP VQLWVTSTPP
160 170 180 190 200
PGTRVRAMAI YKKSQHMTEV VRRCPHHERC SDGDGLAPPQ HLIRVEGNPY
210 220 230 240 250
AEYLDDRQTF RHSVVVPYEP PEVGSDYTTI HYKYMCNSSC MGGMNRRPIL
260 270 280 290 300
TIITLEDSSG NLLGRDSFEV RVCACPGRDR RTEEENFRKK EEHCPELPPG
310 320 330 340 350
SAKRALPTST SSSPQQKKKP LDGEYFTLKI RGRERFEMFR ELNEALELKD
360 370 380 390
ARAAEESGDS RAHSSYPKTK KGQSTSRHKK PMIKKVGPDS D
Length:391
Mass (Da):43,451
Last modified:July 1, 1989 - v1
Checksum:iE62522313A5C872F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti174C → W in AAA41788 (PubMed:8441680).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti103G → S.1
Natural varianti256E → G.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X13058 mRNA. Translation: CAA31457.1.
L07910
, 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.
PIRiS02192.
RefSeqiNP_112251.2. NM_030989.3.
XP_006246656.1. XM_006246594.3.
XP_006246657.1. XM_006246595.3.
UniGeneiRn.54443.

Genome annotation databases

EnsembliENSRNOT00000046490; ENSRNOP00000047840; ENSRNOG00000010756.
ENSRNOT00000085115; ENSRNOP00000074031; ENSRNOG00000010756.
GeneIDi24842.
KEGGirno:24842.
UCSCiRGD:3889. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X13058 mRNA. Translation: CAA31457.1.
L07910
, 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.
PIRiS02192.
RefSeqiNP_112251.2. NM_030989.3.
XP_006246656.1. XM_006246594.3.
XP_006246657.1. XM_006246595.3.
UniGeneiRn.54443.

3D structure databases

ProteinModelPortaliP10361.
SMRiP10361.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246960. 9 interactors.
DIPiDIP-46016N.
IntActiP10361. 4 interactors.
MINTiMINT-4651801.
STRINGi10116.ENSRNOP00000047840.

PTM databases

iPTMnetiP10361.
PhosphoSitePlusiP10361.

Proteomic databases

PaxDbiP10361.
PRIDEiP10361.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000046490; ENSRNOP00000047840; ENSRNOG00000010756.
ENSRNOT00000085115; ENSRNOP00000074031; ENSRNOG00000010756.
GeneIDi24842.
KEGGirno:24842.
UCSCiRGD:3889. rat.

Organism-specific databases

CTDi7157.
RGDi3889. Tp53.

Phylogenomic databases

eggNOGiENOG410IITK. Eukaryota.
ENOG410ZSWV. LUCA.
GeneTreeiENSGT00390000015092.
HOGENOMiHOG000039957.
HOVERGENiHBG005201.
InParanoidiP10361.
KOiK04451.
OMAiVVSTRIC.
PhylomeDBiP10361.
TreeFamiTF106101.

Miscellaneous databases

PROiP10361.

Gene expression databases

BgeeiENSRNOG00000010756.
ExpressionAtlasiP10361. baseline and differential.
GenevisibleiP10361. RN.

Family and domain databases

CDDicd08367. P53. 1 hit.
Gene3Di2.60.40.720. 1 hit.
4.10.170.10. 1 hit.
InterProiIPR008967. 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]
PANTHERiPTHR11447. PTHR11447. 1 hit.
PfamiPF00870. P53. 1 hit.
PF08563. P53_TAD. 1 hit.
PF07710. P53_tetramer. 1 hit.
[Graphical view]
PRINTSiPR00386. P53SUPPRESSR.
SUPFAMiSSF47719. SSF47719. 1 hit.
SSF49417. SSF49417. 1 hit.
PROSITEiPS00348. P53. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiP53_RAT
AccessioniPrimary (citable) accession number: P10361
Secondary accession number(s): O09168, Q4KMA9, Q66HM0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: November 30, 2016
This is version 192 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.