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Protein

Cellular tumor antigen p53

Gene

Tp53

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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 DNA damage stimulus 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 by RNA polymerase II 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 gene expression Source: ARUK-UCL
  • 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 by RNA polymerase II 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 by RNA polymerase II 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

Keywordsi

Molecular functionActivator, DNA-binding, Repressor
Biological processApoptosis, Biological rhythms, Cell cycle, Necrosis, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-2559580 Oxidative Stress Induced Senescence
R-RNO-2559585 Oncogene Induced Senescence
R-RNO-2559586 DNA Damage/Telomere Stress Induced Senescence
R-RNO-349425 Autodegradation of the E3 ubiquitin ligase COP1
R-RNO-5689880 Ub-specific processing proteases
R-RNO-5689896 Ovarian tumor domain proteases
R-RNO-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-RNO-6804754 Regulation of TP53 Expression
R-RNO-6804756 Regulation of TP53 Activity through Phosphorylation
R-RNO-6804757 Regulation of TP53 Degradation
R-RNO-6804758 Regulation of TP53 Activity through Acetylation
R-RNO-6804759 Regulation of TP53 Activity through Association with Co-factors
R-RNO-6804760 Regulation of TP53 Activity through Methylation
R-RNO-6811555 PI5P Regulates TP53 Acetylation
R-RNO-69473 G2/M DNA damage checkpoint
R-RNO-69481 G2/M Checkpoints
R-RNO-69541 Stabilization of p53
R-RNO-69895 Transcriptional activation of cell cycle inhibitor p21
R-RNO-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint
R-RNO-8941855 RUNX3 regulates CDKN1A transcription

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi3889 Tp53

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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, RNF34 and RNF125, which leads to proteasomal degradation. Ubiquitination by TOPORS induces degradation. Deubiquitination by USP7, leading to stabilize it. Ubiquitinated by COP1, 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. Interacts with AXIN1. Probably part of a complex consisting of TP53, HIPK2 and AXIN1 (By similarity). Interacts with histone acetyltransferases EP300 and methyltransferases HRMT1L2 and CARM1, and recruits them to promoters. Interacts (via C-terminus) with TAF1; when TAF1 is part of the TFIID complex. Interacts with ING4; this interaction may be indirect. Found in a complex with CABLES1 and TP73. Interacts with HIPK1, HIPK2, and TP53INP1. Interacts with WWOX. Interacts with USP7 and SYVN1. Interacts with HSP90AB1 (PubMed:8663025). Interacts with CHD8; leading to recruit histone H1 and prevent transactivation activity (By similarity). Interacts with ARMC10, BANP, CDKN2AIP, NUAK1, STK11/LKB1, UHRF2 and E4F1. Interacts with YWHAZ; the interaction enhances TP53 transcriptional activity. Phosphorylation of YWHAZ on 'Ser-58' inhibits this interaction. Interacts (via DNA-binding domain) with MAML1 (via N-terminus). Interacts with MKRN1. Interacts with PML (via C-terminus). Interacts with MDM2; leading to ubiquitination and proteasomal degradation of TP53. Directly interacts with FBXO42; leading to ubiquitination and degradation of TP53. Interacts (phosphorylated at Ser-15 by ATM) with the phosphatase PP2A-PPP2R5C holoenzyme; regulates stress-induced TP53-dependent inhibition of cell proliferation. Interacts with PPP2R2A. 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. Interacts with ZNF385B; the interaction is direct. Interacts (via DNA-binding domain) 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 COP1. Interacts with CCAR2 (via N-terminus). Interacts with MORC3. Interacts (via C-terminus) with POU4F2 (via C-terminus). Interacts (via oligomerization region) with NOP53; the interaction is direct and may prevent the MDM2-mediated proteasomal degradation of TP53. Interacts with AFG1L; mediates mitochondrial translocation of TP53. Interacts with UBD (By similarity).By similarity1 Publication

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, 10 interactors
DIPiDIP-46016N
IntActiP10361, 5 interactors
MINTiP10361
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
InterProiView protein in InterPro
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
IPR013872 p53_transactivation_domain
IPR002117 p53_tumour_suppressor
PANTHERiPTHR11447 PTHR11447, 1 hit
PfamiView protein in Pfam
PF00870 P53, 1 hit
PF08563 P53_TAD, 1 hit
PF07710 P53_tetramer, 1 hit
PRINTSiPR00386 P53SUPPRESSR
SUPFAMiSSF47719 SSF47719, 1 hit
SSF49417 SSF49417, 1 hit
PROSITEiView protein in PROSITE
PS00348 P53, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiP53_RAT
AccessioniPrimary (citable) accession number: P10361
Secondary accession number(s): O09168, Q4KMA9, Q66HM0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: June 20, 2018
This is version 207 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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