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Protein

Cellular tumor antigen p53

Gene

TP53

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 bindingi168ZincBy similarity1
Metal bindingi171ZincBy similarity1
Metal bindingi231ZincBy similarity1
Metal bindingi235ZincBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi94 – 285By similarityAdd BLAST192

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-BTA-2559580. Oxidative Stress Induced Senescence.
R-BTA-2559584. Formation of Senescence-Associated Heterochromatin Foci (SAHF).
R-BTA-2559585. Oncogene Induced Senescence.
R-BTA-2559586. DNA Damage/Telomere Stress Induced Senescence.
R-BTA-3232118. SUMOylation of transcription factors.
R-BTA-349425. Autodegradation of the E3 ubiquitin ligase COP1.
R-BTA-5689880. Ub-specific processing proteases.
R-BTA-5689896. Ovarian tumor domain proteases.
R-BTA-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
R-BTA-6804754. Regulation of TP53 Expression.
R-BTA-6804756. Regulation of TP53 Activity through Phosphorylation.
R-BTA-6804757. Regulation of TP53 Degradation.
R-BTA-6804758. Regulation of TP53 Activity through Acetylation.
R-BTA-6804759. Regulation of TP53 Activity through Association with Co-factors.
R-BTA-6804760. Regulation of TP53 Activity through Methylation.
R-BTA-6811555. PI5P Regulates TP53 Acetylation.
R-BTA-69473. G2/M DNA damage checkpoint.
R-BTA-69481. G2/M Checkpoints.
R-BTA-69541. Stabilization of p53.
R-BTA-69895. Transcriptional activation of cell cycle inhibitor p21.
R-BTA-8852276. The role of GTSE1 in G2/M progression after G2 checkpoint.
R-BTA-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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 19

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_00001856941 – 386Cellular tumor antigen p53Add BLAST386

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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 residuei33Phosphoserine; by CDK5 and CDK7By similarity1
Modified residuei37Phosphoserine; by MAPKAPK5By similarity1
Modified residuei112N6-acetyllysine; by KAT6ABy similarity1
Modified residuei175Phosphoserine; by AURKBBy similarity1
Modified residuei262Phosphoserine; by AURKBBy similarity1
Modified residuei277Phosphothreonine; by AURKBBy similarity1
Cross-linki284Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki285Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei298N6-acetyllysineBy similarity1
Modified residuei308Phosphoserine; by AURKA, CDK1 and CDK2By similarity1
Modified residuei314N6-acetyllysineBy similarity1
Modified residuei363N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei363N6-methyllysine; by SMYD2; alternateBy similarity1
Modified residuei365N6-methyllysine; by SETD7By similarity1
Modified residuei366N6,N6-dimethyllysine; by EHMT1 and EHMT2; alternateBy similarity1
Modified residuei366N6-acetyllysine; alternateBy similarity1
Modified residuei374N6-acetyllysineBy similarity1
Modified residuei375N6,N6-dimethyllysine; alternateBy similarity1
Modified residuei375N6-acetyllysine; by KAT6A; alternateBy similarity1
Modified residuei375N6-methyllysine; by KMT5A; alternateBy similarity1
Cross-linki379Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei385Phosphoserine; by CK2, CDK2 and NUAK1By similarity1

Post-translational modificationi

Phosphorylation on Ser residues mediates transcriptional activation. 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 Ser-33 by CDK7 in a CAK complex in response to DNA damage. Phosphorylated by HIPK1. Phosphorylated on Ser-385 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 and Ser-33, leading to accumulation of p53/TP53, particularly in the nucleus, thus inducing the transactivation of p53/TP53 target genes. Phosphorylated at Ser-308 and Ser-385 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-284 and Lys-285, 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 RFWD2, which leads to proteasomal degradation (By similarity). Ubiquitination and subsequent proteasomal degradation is negatively regulated by CCAR2 (By similarity).By similarity
Monomethylated at Lys-365 by SETD7, leading to stabilization and increased transcriptional activation. Monomethylated at Lys-363 by SMYD2, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity. Lys-365 monomethylation prevents interaction with SMYD2 and subsequent monomethylation at Lys-363. Dimethylated at Lys-366 by EHMT1 and EHMT2. Monomethylated at Lys-375 by KMT5A, promoting interaction with L3MBTL1 and leading to repress transcriptional activity. Demethylation of dimethylated Lys-363 by KDM1A prevents interaction with TP53BP1 and represses TP53-mediated transcriptional activation (By similarity).By similarity
Sumoylated with SUMO1. Sumoylated at Lys-379 by UBC9 (By similarity).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP67939.
PRIDEiP67939.

Expressioni

Gene expression databases

BgeeiENSBTAG00000001069.
ExpressionAtlasiP67939. baseline.

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. 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-375) 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 RFWD2. 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 similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei112Interaction with DNABy similarity1

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000001420.

Structurei

3D structure databases

ProteinModelPortaliP67939.
SMRiP67939.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 313Interaction with CCAR2By similarityAdd BLAST313
Regioni1 – 44Transcription activation (acidic)Add BLAST44
Regioni63 – 102Interaction with WWOXBy similarityAdd BLAST40
Regioni92 – 363Interaction with HIPK1By similarityAdd BLAST272
Regioni92 – 293Required for interaction with ZNF385ABy similarityAdd BLAST202
Regioni105 – 229Required for interaction with FBXO42By similarityAdd BLAST125
Regioni108 – 285Interaction with AXIN1By similarityAdd BLAST178
Regioni249 – 287Interaction with E4F1By similarityAdd BLAST39
Regioni266 – 273Interaction with DNABy similarity8
Regioni312 – 353Interaction with HIPK2By similarityAdd BLAST42
Regioni318 – 349OligomerizationAdd BLAST32
Regioni352 – 356Interaction with USP7By similarity5
Regioni361 – 380Basic (repression of DNA-binding)Add BLAST20

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi298 – 314Bipartite nuclear localization signalBy similarityAdd BLAST17
Motifi332 – 343Nuclear export signalBy similarityAdd BLAST12
Motifi363 – 365[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.
InParanoidiP67939.
KOiK04451.
OMAiPATSWPL.
OrthoDBiEOG091G0XY5.
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.
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.

P67939-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEESQAELNV EPPLSQETFS DLWNLLPENN LLSSELSAPV DDLLPYTDVA
60 70 80 90 100
TWLDECPNEA PQMPEPSAPA APPPATPAPA TSWPLSSFVP SQKTYPGNYG
110 120 130 140 150
FRLGFLQSGT AKSVTCTYSP SLNKLFCQLA KTCPVQLWVD SPPPPGTRVR
160 170 180 190 200
AMAIYKKLEH MTEVVRRCPH HERSSDYSDG LAPPQHLIRV EGNLRAEYLD
210 220 230 240 250
DRNTFRHSVV VPYESPEIDS ECTTIHYNFM CNSSCMGGMN RRPILTIITL
260 270 280 290 300
EDSCGNLLGR NSFEVRVCAC PGRDRRTEEE NLRKKGQSCP EPPPRSTKRA
310 320 330 340 350
LPTNTSSSPQ PKKKPLDGEY FTLQIRGFKR YEMFRELNDA LELKDALDGR
360 370 380
EPGESRAHSS HLKSKKRPSP SCHKKPMLKR EGPDSD
Length:386
Mass (Da):43,256
Last modified:October 11, 2004 - v1
Checksum:i222473F28C548F31
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti380R → T in BAA08629 (PubMed:8807776).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X81704 mRNA. Translation: CAA57348.1.
DQ656490 mRNA. Translation: ABG37911.1.
BC102440 mRNA. Translation: AAI02441.1.
D49825 mRNA. Translation: BAA08629.1.
PIRiS51648.
RefSeqiNP_776626.1. NM_174201.2.
UniGeneiBt.49712.

Genome annotation databases

EnsembliENSBTAT00000001420; ENSBTAP00000001420; ENSBTAG00000001069.
GeneIDi281542.
KEGGibta:281542.

Similar proteinsi

Entry informationi

Entry nameiP53_BOVIN
AccessioniPrimary (citable) accession number: P67939
Secondary accession number(s): Q29628, Q3ZCF1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: October 25, 2017
This is version 141 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families