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Protein

Cellular tumor antigen p53

Gene

Tp53

Organism
Mus musculus (Mouse)
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 (By similarity). 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, but seems to have to effect on cell-cycle regulation. Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2 (PubMed:24051492).By similarity4 Publications

Cofactori

Zn2+Note: Binds 1 zinc ion per subunit.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi170Zinc1
Metal bindingi173Zinc1
Metal bindingi232Zinc1
Metal bindingi236Zinc1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi96 – 286By similarityAdd BLAST191

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-2559580 Oxidative Stress Induced Senescence
R-MMU-2559584 Formation of Senescence-Associated Heterochromatin Foci (SAHF)
R-MMU-2559585 Oncogene Induced Senescence
R-MMU-2559586 DNA Damage/Telomere Stress Induced Senescence
R-MMU-349425 Autodegradation of the E3 ubiquitin ligase COP1
R-MMU-5689880 Ub-specific processing proteases
R-MMU-5689896 Ovarian tumor domain proteases
R-MMU-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-MMU-6804754 Regulation of TP53 Expression
R-MMU-6804756 Regulation of TP53 Activity through Phosphorylation
R-MMU-6804757 Regulation of TP53 Degradation
R-MMU-6804758 Regulation of TP53 Activity through Acetylation
R-MMU-6804759 Regulation of TP53 Activity through Association with Co-factors
R-MMU-6804760 Regulation of TP53 Activity through Methylation
R-MMU-6811555 PI5P Regulates TP53 Acetylation
R-MMU-69473 G2/M DNA damage checkpoint
R-MMU-69481 G2/M Checkpoints
R-MMU-69541 Stabilization of p53
R-MMU-69895 Transcriptional activation of cell cycle inhibitor p21
R-MMU-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint
R-MMU-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, Trp53
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:98834 Trp53

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

Disease mutation, Tumor suppressor

Chemistry databases

ChEMBLiCHEMBL4164

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001857091 – 387Cellular tumor antigen p53Add BLAST387

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei9Phosphoserine; by HIPK41 Publication1
Modified residuei15Phosphoserine; by CDK5, PRPK, AMPK, NUAK1 and ATM1 Publication1
Modified residuei18Phosphothreonine; by CK1, VRK1 and VRK2By similarity1
Modified residuei20Phosphoserine; by CHEK2, CK1 and PLK3By similarity1
Modified residuei34Phosphoserine; by MAPKAPK51 Publication1
Modified residuei114N6-acetyllysine; by KAT6ABy similarity1
Modified residuei177Phosphoserine; by AURKBBy similarity1
Modified residuei263Phosphoserine; by AURKBBy similarity1
Modified residuei278Phosphothreonine; by AURKBBy similarity1
Cross-linki285Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki286Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei299N6-acetyllysineBy similarity1
Modified residuei309Phosphoserine; by AURKA, CDK1 and CDK2By similarity1
Modified residuei315N6-acetyllysineCombined sources1
Modified residuei364N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei364N6-methyllysine; by SMYD2; alternateBy similarity1
Modified residuei366N6-methyllysine; by SETD7By similarity1
Modified residuei367N6,N6-dimethyllysine; by EHMT1 and EHMT2; alternateBy similarity1
Modified residuei367N6-acetyllysine; alternateBy similarity1
Modified residuei375N6-acetyllysineBy similarity1
Modified residuei376N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei376N6-acetyllysine; by KAT6A; alternateBy similarity1
Modified residuei376N6-methyllysine; by KMT5A; alternateBy similarity1
Cross-linki380Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei386Phosphoserine; by CK2, CDK2 and NUAK1By similarity1

Post-translational modificationi

Phosphorylated on Ser-15 upon ultraviolet irradiation; which is enhanced by interaction with BANP (By similarity). Phosphorylation on Ser residues mediates transcriptional activation. Phosphorylation at Ser-9 by HIPK4 increases repression activity on BIRC5 promoter. Phosphorylated on Thr-18 by VRK1. 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. 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 (By similarity). Phosphorylated on Ser-386 following UV but not gamma irradiation. Phosphorylated by HIPK1.By similarity7 Publications
Deacetylation by SIRT2 impairs its ability to induce transcription activation in a AKT-dependent manner (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-285 and Lys-286, 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 (By similarity). Ubiquitination and subsequent proteasomal degradation is negatively regulated by CCAR2 (PubMed:25732823).By similarity1 Publication
Monomethylated at Lys-366 by SETD7, leading to stabilization and increased transcriptional activation. Monomethylated at Lys-364 by SMYD2, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity. Lys-366 monomethylation prevents interaction with SMYD2 and subsequent monomethylation at Lys-364. Dimethylated at Lys-367 EHMT1 and EHMT2. Monomethylated at Lys-376 KMT5A, promoting interaction with L3MBTL1 and leading to repress transcriptional activity. Demethylation of dimethylated Lys-364 by KDM1A prevents interaction with TP53BP1 and represses TP53-mediated transcriptional activation (By similarity).By similarity
Sumoylated with SUMO1. Sumoylated at Lys-380 by UBC9 (By similarity).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP02340
MaxQBiP02340
PaxDbiP02340
PRIDEiP02340

PTM databases

iPTMnetiP02340
PhosphoSitePlusiP02340
SwissPalmiP02340

Expressioni

Inductioni

Expressed in a circadian manner in the suprachiasmatic nucleus (SCN) of the brain with a peak seen at ZT8.1 Publication

Gene expression databases

BgeeiENSMUSG00000059552 Expressed in 258 organ(s), highest expression level in embryo
CleanExiMM_TRP53
ExpressionAtlasiP02340 baseline and differential
GenevisibleiP02340 MM

Interactioni

Subunit structurei

Binds DNA as a homotetramer. Interacts with AXIN1 (PubMed:15526030). Probably part of a complex consisting of TP53, HIPK2 and AXIN1 (PubMed:15526030). 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 (PubMed:12702766). Found in a complex with CABLES1 and TP73 (PubMed:11706030). Interacts with HIPK1, HIPK2, and TP53INP1. Interacts with WWOX. Interacts with USP7 and SYVN1 (PubMed:14719112). Interacts with HSP90AB1. Interacts with CHD8; leading to recruit histone H1 and prevent transactivation activity (PubMed:19151705). Interacts with ARMC10, BANP, CDKN2AIP, NUAK1, STK11/LKB1, UHRF2 and E4F (PubMed:10644996). 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 (PubMed:19556538). Interacts (when monomethylated at Lys-376) 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 (PubMed:17719541). 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 similarity9 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei114Interaction with DNA1

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204323, 116 interactors
CORUMiP02340
DIPiDIP-369N
IntActiP02340, 44 interactors
MINTiP02340
STRINGi10090.ENSMUSP00000104298

Structurei

Secondary structure

1387
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP02340
SMRiP02340
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP02340

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 314Interaction with CCAR2By similarityAdd BLAST314
Regioni1 – 42Transcription activation (acidic)Add BLAST42
Regioni60 – 104Interaction with WWOXBy similarityAdd BLAST45
Regioni94 – 364Interaction with HIPK11 PublicationAdd BLAST271
Regioni94 – 294Required for interaction with ZNF385ABy similarityAdd BLAST201
Regioni107 – 230Required for interaction with FBXO42By similarityAdd BLAST124
Regioni110 – 286Interaction with AXIN11 PublicationAdd BLAST177
Regioni253 – 291Interaction with E4F1By similarityAdd BLAST39
Regioni267 – 274Interaction with DNA8
Regioni313 – 354Interaction with HIPK2By similarityAdd BLAST42
Regioni319 – 350OligomerizationAdd BLAST32
Regioni353 – 357Interaction with USP7By similarity5
Regioni362 – 381Basic (repression of DNA-binding)Add BLAST20

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi299 – 315Bipartite nuclear localization signalBy similarityAdd BLAST17
Motifi333 – 344Nuclear export signalBy similarityAdd BLAST12
Motifi364 – 366[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
InParanoidiP02340
KOiK04451

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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.iShow all

P02340-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MEESQSDISL ELPLSQETFS GLWKLLPPED ILPSPHCMDD LLLPQDVEEF
60 70 80 90 100
FEGPSEALRV SGAPAAQDPV TETPGPVAPA PATPWPLSSF VPSQKTYQGN
110 120 130 140 150
YGFHLGFLQS GTAKSVMCTY SPPLNKLFCQ LAKTCPVQLW VSATPPAGSR
160 170 180 190 200
VRAMAIYKKS QHMTEVVRRC PHHERCSDGD GLAPPQHLIR VEGNLYPEYL
210 220 230 240 250
EDRQTFRHSV VVPYEPPEAG SEYTTIHYKY MCNSSCMGGM NRRPILTIIT
260 270 280 290 300
LEDSSGNLLG RDSFEVRVCA CPGRDRRTEE ENFRKKEVLC PELPPGSAKR
310 320 330 340 350
ALPTCTSASP PQKKKPLDGE YFTLKIRGRK RFEMFRELNE ALELKDAHAT
360 370 380
EESGDSRAHS SYLKTKKGQS TSRHKKTMVK KVGPDSD
Length:387
Mass (Da):43,155
Last modified:March 18, 2008 - v3
Checksum:iB55EB7B463E1DD9D
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q549C9Q549C9_MOUSE
Cellular tumor antigen p53
Trp53 p53, mCG_20908
390Annotation score:
Q80ZA1Q80ZA1_MOUSE
Cellular tumor antigen p53
Trp53
381Annotation score:
I7HIK9I7HIK9_MOUSE
Cellular tumor antigen p53
Trp53 RP23-56I20.1-002
378Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti45Q → R in CAA25323 (PubMed:6379601).Curated1
Sequence conflicti76 – 78PVA → QW in CAA25323 (PubMed:6379601).Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti132A → V Can cooperate with an activated Ras to transform fibroblasts. 1 Publication1
Natural varianti165E → G in clone P53-M11. 1
Natural varianti188L → R. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X00876
, X00877, X00878, X00879, X00880, X00881, X00882, X00883, X00884, X00885 Genomic DNA Translation: CAA25420.1
X01237 mRNA Translation: CAA25625.1
X00741 mRNA Translation: CAA25323.1
M13872 mRNA Translation: AAA39881.1
M13873 mRNA Translation: AAA39882.1
M13874 mRNA Translation: AAA39883.1 Sequence problems.
AB021961 mRNA Translation: BAA82344.1
AF151353 mRNA Translation: AAD39535.1
AB017815 mRNA Translation: BAA82339.1
AB017816 mRNA Translation: BAA82340.1
AB020317 mRNA Translation: BAA82343.1
BC005448 mRNA Translation: AAH05448.1
S77930 Genomic DNA Translation: AAB21108.2
PIRiA22739 DNMS53
S38824
RefSeqiNP_001120705.1, NM_001127233.1
NP_035770.2, NM_011640.3
XP_006533220.1, XM_006533157.3
UniGeneiMm.222

Genome annotation databases

EnsembliENSMUST00000005371; ENSMUSP00000005371; ENSMUSG00000059552
GeneIDi22059
KEGGimmu:22059
UCSCiuc007jql.2 mouse

Similar proteinsi

Entry informationi

Entry nameiP53_MOUSE
AccessioniPrimary (citable) accession number: P02340
Secondary accession number(s): Q9QUP3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: March 18, 2008
Last modified: September 12, 2018
This is version 231 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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