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O15297

- PPM1D_HUMAN

UniProt

O15297 - PPM1D_HUMAN

Protein

Protein phosphatase 1D

Gene

PPM1D

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 133 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    Functioni

    Required for the relief of p53-dependent checkpoint mediated cell cycle arrest. Binds to and dephosphorylates 'Ser-15' of TP53 and 'Ser-345' of CHEK1 which contributes to the functional inactivation of these proteins.2 Publications

    Catalytic activityi

    [a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

    Cofactori

    Binds 2 magnesium or manganese ions per subunit.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi105 – 1051Manganese 1By similarity
    Metal bindingi105 – 1051Manganese 2By similarity
    Metal bindingi106 – 1061Manganese 1; via carbonyl oxygenBy similarity
    Metal bindingi314 – 3141Manganese 2By similarity
    Metal bindingi366 – 3661Manganese 2By similarity

    GO - Molecular functioni

    1. metal ion binding Source: UniProtKB-KW
    2. protein binding Source: IntAct
    3. protein serine/threonine phosphatase activity Source: UniProtKB

    GO - Biological processi

    1. G2/M transition of mitotic cell cycle Source: Ensembl
    2. negative regulation of cell proliferation Source: ProtInc
    3. peptidyl-threonine dephosphorylation Source: UniProtKB
    4. protein dephosphorylation Source: ProtInc
    5. response to bacterium Source: Ensembl
    6. response to radiation Source: ProtInc

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Keywords - Biological processi

    Cell cycle

    Keywords - Ligandi

    Magnesium, Manganese, Metal-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein phosphatase 1D (EC:3.1.3.16)
    Alternative name(s):
    Protein phosphatase 2C isoform delta
    Short name:
    PP2C-delta
    Protein phosphatase magnesium-dependent 1 delta
    p53-induced protein phosphatase 1
    Gene namesi
    Name:PPM1D
    Synonyms:WIP1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:9277. PPM1D.

    Subcellular locationi

    GO - Cellular componenti

    1. nucleus Source: ProtInc

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi314 – 3141D → A: Abrogates phosphatase activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA33605.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 605605Protein phosphatase 1DPRO_0000057752Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei40 – 401Phosphoserine1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO15297.
    PaxDbiO15297.
    PRIDEiO15297.

    PTM databases

    PhosphoSiteiO15297.

    Expressioni

    Inductioni

    By p53/TP53.2 Publications

    Gene expression databases

    ArrayExpressiO15297.
    BgeeiO15297.
    CleanExiHS_PPM1D.
    GenevestigatoriO15297.

    Organism-specific databases

    HPAiCAB009474.
    HPA022277.

    Interactioni

    Subunit structurei

    Interacts with CHEK1 and CHEK2; dephosphorylates them.2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    H2AFXP161046EBI-1551512,EBI-494830
    MDM2Q009874EBI-1551512,EBI-389668

    Protein-protein interaction databases

    BioGridi114065. 6 interactions.
    DIPiDIP-38281N.
    IntActiO15297. 4 interactions.
    MINTiMINT-7944722.
    STRINGi9606.ENSP00000306682.

    Structurei

    3D structure databases

    ProteinModelPortaliO15297.
    SMRiO15297. Positions 99-374.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini61 – 378318PP2C-likeAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 101101Interaction with CHEK1Add
    BLAST

    Sequence similaritiesi

    Belongs to the PP2C family.Curated
    Contains 1 PP2C-like domain.Curated

    Phylogenomic databases

    eggNOGiCOG0631.
    HOGENOMiHOG000231949.
    HOVERGENiHBG058897.
    InParanoidiO15297.
    KOiK10147.
    OMAiVIPSKDP.
    OrthoDBiEOG7Z95M0.
    PhylomeDBiO15297.
    TreeFamiTF313481.

    Family and domain databases

    Gene3Di3.60.40.10. 2 hits.
    InterProiIPR001932. PP2C-like_dom.
    IPR000222. PP2C_Mn2_Asp60_BS.
    IPR015655. Protein_Pase_2C.
    [Graphical view]
    PANTHERiPTHR13832. PTHR13832. 1 hit.
    PfamiPF00481. PP2C. 1 hit.
    [Graphical view]
    SMARTiSM00332. PP2Cc. 1 hit.
    [Graphical view]
    SUPFAMiSSF81606. SSF81606. 2 hits.
    PROSITEiPS01032. PP2C. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O15297-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAGLYSLGVS VFSDQGGRKY MEDVTQIVVE PEPTAEEKPS PRRSLSQPLP    50
    PRPSPAALPG GEVSGKGPAV AAREARDPLP DAGASPAPSR CCRRRSSVAF 100
    FAVCDGHGGR EAAQFAREHL WGFIKKQKGF TSSEPAKVCA AIRKGFLACH 150
    LAMWKKLAEW PKTMTGLPST SGTTASVVII RGMKMYVAHV GDSGVVLGIQ 200
    DDPKDDFVRA VEVTQDHKPE LPKERERIEG LGGSVMNKSG VNRVVWKRPR 250
    LTHNGPVRRS TVIDQIPFLA VARALGDLWS YDFFSGEFVV SPEPDTSVHT 300
    LDPQKHKYII LGSDGLWNMI PPQDAISMCQ DQEEKKYLMG EHGQSCAKML 350
    VNRALGRWRQ RMLRADNTSA IVICISPEVD NQGNFTNEDE LYLNLTDSPS 400
    YNSQETCVMT PSPCSTPPVK SLEEDPWPRV NSKDHIPALV RSNAFSENFL 450
    EVSAEIAREN VQGVVIPSKD PEPLEENCAK ALTLRIHDSL NNSLPIGLVP 500
    TNSTNTVMDQ KNLKMSTPGQ MKAQEIERTP PTNFKRTLEE SNSGPLMKKH 550
    RRNGLSRSSG AQPASLPTTS QRKNSVKLTM RRRLRGQKKI GNPLLHQHRK 600
    TVCVC 605
    Length:605
    Mass (Da):66,675
    Last modified:January 1, 1998 - v1
    Checksum:iE6C5884CF04008B7
    GO
    Isoform 2 (identifier: O15297-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         421-430: SLEEDPWPRV → DFGFELDSRK
         431-605: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:430
    Mass (Da):47,211
    Checksum:iFD242857BFE6D5D9
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti322 – 3221P → Q.1 Publication
    Corresponds to variant rs17855093 [ dbSNP | Ensembl ].
    VAR_070430

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei421 – 43010SLEEDPWPRV → DFGFELDSRK in isoform 2. 1 PublicationVSP_056377
    Alternative sequencei431 – 605175Missing in isoform 2. 1 PublicationVSP_056378Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U78305 mRNA. Translation: AAB61637.1.
    BT009780 mRNA. Translation: AAP88782.1.
    AC011921 Genomic DNA. No translation available.
    AC110602 Genomic DNA. No translation available.
    AC111155 Genomic DNA. No translation available.
    CH471179 Genomic DNA. Translation: EAW51408.1.
    CH471179 Genomic DNA. Translation: EAW51409.1.
    BC016480 mRNA. Translation: AAH16480.1.
    BC042418 mRNA. Translation: AAH42418.1.
    BC060877 mRNA. Translation: AAH60877.1.
    CCDSiCCDS11625.1.
    RefSeqiNP_003611.1. NM_003620.3.
    UniGeneiHs.286073.

    Genome annotation databases

    EnsembliENST00000305921; ENSP00000306682; ENSG00000170836.
    ENST00000392995; ENSP00000376720; ENSG00000170836.
    GeneIDi8493.
    KEGGihsa:8493.
    UCSCiuc002iyt.2. human.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U78305 mRNA. Translation: AAB61637.1 .
    BT009780 mRNA. Translation: AAP88782.1 .
    AC011921 Genomic DNA. No translation available.
    AC110602 Genomic DNA. No translation available.
    AC111155 Genomic DNA. No translation available.
    CH471179 Genomic DNA. Translation: EAW51408.1 .
    CH471179 Genomic DNA. Translation: EAW51409.1 .
    BC016480 mRNA. Translation: AAH16480.1 .
    BC042418 mRNA. Translation: AAH42418.1 .
    BC060877 mRNA. Translation: AAH60877.1 .
    CCDSi CCDS11625.1.
    RefSeqi NP_003611.1. NM_003620.3.
    UniGenei Hs.286073.

    3D structure databases

    ProteinModelPortali O15297.
    SMRi O15297. Positions 99-374.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114065. 6 interactions.
    DIPi DIP-38281N.
    IntActi O15297. 4 interactions.
    MINTi MINT-7944722.
    STRINGi 9606.ENSP00000306682.

    Chemistry

    BindingDBi O15297.
    ChEMBLi CHEMBL1938224.

    PTM databases

    PhosphoSitei O15297.

    Proteomic databases

    MaxQBi O15297.
    PaxDbi O15297.
    PRIDEi O15297.

    Protocols and materials databases

    DNASUi 8493.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000305921 ; ENSP00000306682 ; ENSG00000170836 .
    ENST00000392995 ; ENSP00000376720 ; ENSG00000170836 .
    GeneIDi 8493.
    KEGGi hsa:8493.
    UCSCi uc002iyt.2. human.

    Organism-specific databases

    CTDi 8493.
    GeneCardsi GC17P058677.
    HGNCi HGNC:9277. PPM1D.
    HPAi CAB009474.
    HPA022277.
    MIMi 605100. gene.
    neXtProti NX_O15297.
    PharmGKBi PA33605.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0631.
    HOGENOMi HOG000231949.
    HOVERGENi HBG058897.
    InParanoidi O15297.
    KOi K10147.
    OMAi VIPSKDP.
    OrthoDBi EOG7Z95M0.
    PhylomeDBi O15297.
    TreeFami TF313481.

    Miscellaneous databases

    GeneWikii PPM1D.
    GenomeRNAii 8493.
    NextBioi 31775.
    PROi O15297.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O15297.
    Bgeei O15297.
    CleanExi HS_PPM1D.
    Genevestigatori O15297.

    Family and domain databases

    Gene3Di 3.60.40.10. 2 hits.
    InterProi IPR001932. PP2C-like_dom.
    IPR000222. PP2C_Mn2_Asp60_BS.
    IPR015655. Protein_Pase_2C.
    [Graphical view ]
    PANTHERi PTHR13832. PTHR13832. 1 hit.
    Pfami PF00481. PP2C. 1 hit.
    [Graphical view ]
    SMARTi SM00332. PP2Cc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF81606. SSF81606. 2 hits.
    PROSITEi PS01032. PP2C. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner."
      Fiscella M., Zhang H., Fan S., Sakaguchi K., Shen S., Mercer W.E., Vande Woude G.F., O'Connor P.M., Appella E.
      Proc. Natl. Acad. Sci. U.S.A. 94:6048-6053(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION.
    2. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    3. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
      Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
      , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
      Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT GLN-322.
      Tissue: Brain and Skin.
    6. "PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints."
      Lu X., Nannenga B., Donehower L.A.
      Genes Dev. 19:1162-1174(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH CHEK1, INDUCTION, MUTAGENESIS OF ASP-314.
    7. "Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase."
      Fujimoto H., Onishi N., Kato N., Takekawa M., Xu X.Z., Kosugi A., Kondo T., Imamura M., Oishi I., Yoda A., Minami Y.
      Cell Death Differ. 13:1170-1180(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN APOPTOSIS, FUNCTION IN DEPHOSPHORYLATION OF CHEK2, INTERACTION WITH CHEK2.
    8. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.

    Entry informationi

    Entry nameiPPM1D_HUMAN
    AccessioniPrimary (citable) accession number: O15297
    Secondary accession number(s): Q53XP4, Q6P991, Q8IVR6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 133 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3