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P13481

- P53_CHLAE

UniProt

P13481 - P53_CHLAE

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Protein
Cellular tumor antigen p53
Gene
TP53
Organism
Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops)
Status
Reviewed - 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 By similarity.

Cofactori

Binds 1 zinc ion per subunit By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei120 – 1201Interaction with DNA By similarity
Metal bindingi176 – 1761Zinc By similarity
Metal bindingi179 – 1791Zinc By similarity
Metal bindingi238 – 2381Zinc By similarity
Metal bindingi242 – 2421Zinc By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi102 – 292191 By similarity
Add
BLAST

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. DNA binding Source: UniProtKB
  3. copper ion binding Source: UniProtKB
  4. sequence-specific DNA binding transcription factor activity Source: InterPro
  5. transcription regulatory region DNA binding Source: InterPro

GO - Biological processi

  1. DNA strand renaturation Source: UniProtKB
  2. cell aging Source: UniProtKB
  3. cell cycle Source: UniProtKB-KW
  4. multicellular organismal development Source: UniProtKB
  5. negative regulation of cell growth Source: UniProtKB
  6. nucleotide-excision repair Source: UniProtKB
  7. oligodendrocyte apoptotic process Source: UniProtKB
  8. positive regulation of release of cytochrome c from mitochondria Source: UniProtKB
  9. protein tetramerization Source: InterPro
  10. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Apoptosis, 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
OrganismiChlorocebus aethiops (Green monkey) (Cercopithecus aethiops)
Taxonomic identifieri9534 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeChlorocebus

Subcellular locationi

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

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. endoplasmic reticulum Source: UniProtKB-SubCell
  3. mitochondrial matrix Source: UniProtKB-SubCell
  4. mitochondrion Source: UniProtKB
  5. nucleolus Source: UniProtKB
  6. nucleus Source: UniProtKB
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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 393393Cellular tumor antigen p53
PRO_0000185697Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei9 – 91Phosphoserine; by HIPK4 By similarity
Modified residuei15 – 151Phosphoserine; by CDK5, PRPK, AMPK, NUAK1 and ATM By similarity
Modified residuei18 – 181Phosphothreonine; by CK1, VRK1 and VRK2 By similarity
Modified residuei20 – 201Phosphoserine; by CHEK2, CK1 and PLK3 By similarity
Modified residuei33 – 331Phosphoserine; by CDK5 and CDK7 By similarity
Modified residuei37 – 371Phosphoserine; by MAPKAPK5 By similarity
Modified residuei46 – 461Phosphoserine; by CDK5, DYRK2, HIPK2 and PKC/PRKCG By similarity
Modified residuei55 – 551Phosphothreonine; by TAF1 and GRK5; alternate By similarity
Modified residuei55 – 551Phosphothreonine; by TAF1; alternate By similarity
Modified residuei120 – 1201N6-acetyllysine; by KAT6A By similarity
Modified residuei183 – 1831Phosphoserine; by AURKB By similarity
Modified residuei269 – 2691Phosphoserine; by AURKB By similarity
Modified residuei284 – 2841Phosphothreonine; by AURKB By similarity
Cross-linki291 – 291Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-linki292 – 292Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Modified residuei305 – 3051N6-acetyllysine By similarity
Modified residuei315 – 3151Phosphoserine; by AURKA, CDK1 and CDK2 By similarity
Modified residuei321 – 3211N6-acetyllysine By similarity
Modified residuei370 – 3701N6,N6-dimethyllysine; alternate By similarity
Modified residuei370 – 3701N6-methyllysine; by SMYD2; alternate By similarity
Modified residuei372 – 3721N6-methyllysine; by SETD7 By similarity
Modified residuei373 – 3731N6,N6-dimethyllysine; by EHMT1 and EHMT2; alternate By similarity
Modified residuei373 – 3731N6-acetyllysine; alternate By similarity
Modified residuei381 – 3811N6-acetyllysine By similarity
Modified residuei382 – 3821N6,N6-dimethyllysine; alternate By similarity
Modified residuei382 – 3821N6-acetyllysine; by KAT6A; alternate By similarity
Modified residuei382 – 3821N6-methyllysine; by SETD8; alternate By similarity
Cross-linki386 – 386Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Modified residuei392 – 3921Phosphoserine; by CK2, CDK2 and NUAK1 By similarity

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. Phosphorylated on Thr-55 by TAF1 which promotes MDM2-mediated TP53 degradation. Phosphorylated on Ser-33 by CDK7 in a CAK complex in response to DNA damage. Phosphorylated by HIPK1. Phosphorylated on Ser-46 by HIPK2 upon UV irradiation. Phosphorylation on Ser-46 is required for acetylation by CREBBP. Phosphorylated on Ser-392 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, Ser-33 and Ser-46, leading to accumulation of p53/TP53, particularly in the nucleus, thus inducing the transactivation of p53/TP53 target genes. Phosphorylated by DYRK2 at Ser-46 in response to genotoxic stress. Phosphorylated at Ser-315 and Ser-392 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. Deacetylation by SIRT2 impairs its ability to induce transcription activation in a AKT-dependent manner 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-291 and Lys-292, 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-372 by SETD7, leading to stabilization and increased transcriptional activation. Monomethylated at Lys-370 by SMYD2, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity. Lys-372 monomethylation prevents interaction with SMYD2 and subsequent monomethylation at Lys-370. Dimethylated at Lys-373 by EHMT1 and EHMT2. Monomethylated at Lys-382 by SETD8, promoting interaction with L3MBTL1 and leading to repress transcriptional activity. Demethylation of dimethylated Lys-370 by KDM1A prevents interaction with TP53BP1 and represses TP53-mediated transcriptional activation By similarity.
Sumoylated with SUMO1. Sumoylated at Lys-386 by UBC9 By similarity.

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

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 HSP90AB1. Interacts with ARMD10, BANP, CDKN2AIP, NUAK1, STK11/LKB1, UHRF2 and E4F1. 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. Directly interacts with FBXO42; leading to ubiquitination and degradation of TP53. Interacts with AURKA, DAXX, BRD7 and TRIM24. Interacts (when monomethylated at Lys-382) 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 (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 By similarity. Interacts with ANKRD2 By similarity. Interacts with RFFL (via RING-type zinc finger); involved in p53/TP53 ubiquitination By similarity.

Structurei

3D structure databases

ProteinModelPortaliP13481.
SMRiP13481. Positions 94-297, 325-356.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 8383Interaction with HRMT1L2 By similarity
Add
BLAST
Regioni1 – 4444Transcription activation (acidic)
Add
BLAST
Regioni66 – 11045Interaction with WWOX By similarity
Add
BLAST
Regioni100 – 370271Interaction with HIPK1 By similarity
Add
BLAST
Regioni100 – 300201Required for interaction with ZNF385A By similarity
Add
BLAST
Regioni113 – 236124Required for interaction with FBXO42 By similarity
Add
BLAST
Regioni116 – 292177Interaction with AXIN1 By similarity
Add
BLAST
Regioni256 – 29439Interaction with E4F1 By similarity
Add
BLAST
Regioni273 – 2808Interaction with DNA By similarity
Regioni300 – 39394Interaction with CARM1 By similarity
Add
BLAST
Regioni319 – 36042Interaction with HIPK2 By similarity
Add
BLAST
Regioni325 – 35632Oligomerization
Add
BLAST
Regioni359 – 3635Interaction with USP7 By similarity
Regioni368 – 38720Basic (repression of DNA-binding)
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi305 – 32117Bipartite nuclear localization signal By similarity
Add
BLAST
Motifi339 – 35012Nuclear export signal By similarity
Add
BLAST
Motifi370 – 3723[KR]-[STA]-K motif

Domaini

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

Sequence similaritiesi

Belongs to the p53 family.

Phylogenomic databases

HOVERGENiHBG005201.

Family and domain databases

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.

P13481-1 [UniParc]FASTAAdd to Basket

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MEEPQSDPSI EPPLSQETFS DLWKLLPENN VLSPLPSQAV DDLMLSPDDL    50
AQWLTEDPGP DEAPRMSEAA PHMAPTPAAP TPAAPAPAPS WPLSSSVPSQ 100
KTYHGSYGFR LGFLHSGTAK SVTCTYSPDL NKMFCQLAKT CPVQLWVDST 150
PPPGSRVRAM AIYKQSQHMT EVVRRCPHHE RCSDSDGLAP PQHLIRVEGN 200
LRVEYSDDRN TFRHSVVVPY EPPEVGSDCT TIHYNYMCNS SCMGGMNRRP 250
ILTIITLEDS SGNLLGRNSF EVRVCACPGR DRRTEEENFR KKGEPCHELP 300
PGSTKRALPN NTSSSPQPKK KPLDGEYFTL QIRGRERFEM FRELNEALEL 350
KDAQAGKEPA GSRAHSSHLK SKKGQSTSRH KKFMFKTEGP DSD 393
Length:393
Mass (Da):43,696
Last modified:January 1, 1990 - v1
Checksum:i9ED285C9A7855D6E
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X16384 mRNA. Translation: CAA34420.1.
PIRiS06594.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X16384 mRNA. Translation: CAA34420.1 .
PIRi S06594.

3D structure databases

ProteinModelPortali P13481.
SMRi P13481. Positions 94-297, 325-356.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Phylogenomic databases

HOVERGENi HBG005201.

Family and domain databases

Gene3Di 2.60.40.720. 1 hit.
4.10.170.10. 1 hit.
InterProi IPR008967. 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 ]
PANTHERi PTHR11447. PTHR11447. 1 hit.
Pfami PF00870. P53. 1 hit.
PF08563. P53_TAD. 1 hit.
PF07710. P53_tetramer. 1 hit.
[Graphical view ]
PRINTSi PR00386. P53SUPPRESSR.
SUPFAMi SSF47719. SSF47719. 1 hit.
SSF49417. SSF49417. 1 hit.
PROSITEi PS00348. P53. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Nucleotide sequence of a cDNA encoding the monkey cellular phosphoprotein p53."
    Rigaudy P., Eckhardt W.
    Nucleic Acids Res. 17:8375-8375(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Liver.

Entry informationi

Entry nameiP53_CHLAE
AccessioniPrimary (citable) accession number: P13481
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: September 3, 2014
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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