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P13481

- P53_CHLAE

UniProt

P13481 - P53_CHLAE

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
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    • History
      Entry version 147 (01 Oct 2014)
      Sequence version 1 (01 Jan 1990)
      Previous versions | rss
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    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.By similarity

    Cofactori

    Binds 1 zinc ion per subunit.By similarity

    Sites

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

    Regions

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

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB
    2. copper ion binding Source: UniProtKB
    3. DNA 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. cell aging Source: UniProtKB
    2. cell cycle Source: UniProtKB-KW
    3. DNA strand renaturation Source: UniProtKB
    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

    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.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

    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 p53PRO_0000185697Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei9 – 91Phosphoserine; by HIPK4By similarity
    Modified residuei15 – 151Phosphoserine; by CDK5, PRPK, AMPK, NUAK1 and ATMBy similarity
    Modified residuei18 – 181Phosphothreonine; by CK1, VRK1 and VRK2By similarity
    Modified residuei20 – 201Phosphoserine; by CHEK2, CK1 and PLK3By similarity
    Modified residuei33 – 331Phosphoserine; by CDK5 and CDK7By similarity
    Modified residuei37 – 371Phosphoserine; by MAPKAPK5By similarity
    Modified residuei46 – 461Phosphoserine; by CDK5, DYRK2, HIPK2 and PKC/PRKCGBy similarity
    Modified residuei55 – 551Phosphothreonine; by TAF1 and GRK5; alternateBy similarity
    Modified residuei55 – 551Phosphothreonine; by TAF1; alternateBy similarity
    Modified residuei120 – 1201N6-acetyllysine; by KAT6ABy similarity
    Modified residuei183 – 1831Phosphoserine; by AURKBBy similarity
    Modified residuei269 – 2691Phosphoserine; by AURKBBy similarity
    Modified residuei284 – 2841Phosphothreonine; by AURKBBy 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-acetyllysineBy similarity
    Modified residuei315 – 3151Phosphoserine; by AURKA, CDK1 and CDK2By similarity
    Modified residuei321 – 3211N6-acetyllysineBy similarity
    Modified residuei370 – 3701N6,N6-dimethyllysine; alternateBy similarity
    Modified residuei370 – 3701N6-methyllysine; by SMYD2; alternateBy similarity
    Modified residuei372 – 3721N6-methyllysine; by SETD7By similarity
    Modified residuei373 – 3731N6,N6-dimethyllysine; by EHMT1 and EHMT2; alternateBy similarity
    Modified residuei373 – 3731N6-acetyllysine; alternateBy similarity
    Modified residuei381 – 3811N6-acetyllysineBy similarity
    Modified residuei382 – 3821N6,N6-dimethyllysine; alternateBy similarity
    Modified residuei382 – 3821N6-acetyllysine; by KAT6A; alternateBy similarity
    Modified residuei382 – 3821N6-methyllysine; by SETD8; alternateBy similarity
    Cross-linki386 – 386Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
    Modified residuei392 – 3921Phosphoserine; by CK2, CDK2 and NUAK1By 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.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-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. Ubiquitinated by RFWD2, which leads to proteasomal degradation By similarity.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.By similarity
    Sumoylated with SUMO1. Sumoylated at Lys-386 by UBC9 By similarity.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. Interacts with MTA1 and RFWD2 By similarity.By similarity

    Structurei

    3D structure databases

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

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 8383Interaction with HRMT1L2By similarityAdd
    BLAST
    Regioni1 – 4444Transcription activation (acidic)Add
    BLAST
    Regioni66 – 11045Interaction with WWOXBy similarityAdd
    BLAST
    Regioni100 – 370271Interaction with HIPK1By similarityAdd
    BLAST
    Regioni100 – 300201Required for interaction with ZNF385ABy similarityAdd
    BLAST
    Regioni113 – 236124Required for interaction with FBXO42By similarityAdd
    BLAST
    Regioni116 – 292177Interaction with AXIN1By similarityAdd
    BLAST
    Regioni256 – 29439Interaction with E4F1By similarityAdd
    BLAST
    Regioni273 – 2808Interaction with DNABy similarity
    Regioni300 – 39394Interaction with CARM1By similarityAdd
    BLAST
    Regioni319 – 36042Interaction with HIPK2By similarityAdd
    BLAST
    Regioni325 – 35632OligomerizationAdd
    BLAST
    Regioni359 – 3635Interaction with USP7By similarity
    Regioni368 – 38720Basic (repression of DNA-binding)Add
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi305 – 32117Bipartite nuclear localization signalBy similarityAdd
    BLAST
    Motifi339 – 35012Nuclear export signalBy similarityAdd
    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.Curated

    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

    « Hide

    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: October 1, 2014
    This is version 147 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