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Q8WY54

- PPM1E_HUMAN

UniProt

Q8WY54 - PPM1E_HUMAN

Protein

Protein phosphatase 1E

Gene

PPM1E

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 97 (01 Oct 2014)
      Sequence version 2 (02 Nov 2010)
      Previous versions | rss
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    Functioni

    Protein phosphatase that inactivates multifunctional CaM kinases such as CAMK4 and CAMK2 By similarity. Dephosphorylates and inactivates PAK. May play a role in the inhibition of actin fiber stress breakdown and in morphological changes driven by TNK2/CDC42. Dephosphorylates PRKAA2 By similarity.By similarity

    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 bindingi282 – 2821Manganese 1By similarity
    Metal bindingi282 – 2821Manganese 2By similarity
    Metal bindingi283 – 2831Manganese 1; via carbonyl oxygenBy similarity
    Metal bindingi444 – 4441Manganese 2By similarity
    Metal bindingi488 – 4881Manganese 2By similarity

    GO - Molecular functioni

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

    GO - Biological processi

    1. cellular response to drug Source: UniProtKB
    2. negative regulation of protein kinase activity Source: UniProtKB
    3. peptidyl-threonine dephosphorylation Source: UniProtKB
    4. positive regulation of stress fiber assembly Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Keywords - Ligandi

    Magnesium, Manganese, Metal-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein phosphatase 1E (EC:3.1.3.16)
    Alternative name(s):
    Ca(2+)/calmodulin-dependent protein kinase phosphatase N
    Short name:
    CaMKP-N
    CaMKP-nucleus
    Short name:
    CaMKN
    Partner of PIX 1
    Partner of PIX-alpha
    Short name:
    Partner of PIXA
    Gene namesi
    Name:PPM1E
    Synonyms:CAMKN, KIAA1072, POPX1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:19322. PPM1E.

    Subcellular locationi

    Nucleus. Cytoplasm
    Note: A truncated form, major form, with the C-terminal part missing, is mostly found in the cytoplasm and a little in the nucleus. The full length, minor form, is found in the nucleus.

    GO - Cellular componenti

    1. mitochondrion Source: Ensembl
    2. nucleolus Source: HPA
    3. nucleus Source: HPA
    4. protein complex Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134943567.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 764764Protein phosphatase 1EPRO_0000286820Add
    BLAST

    Proteomic databases

    MaxQBiQ8WY54.
    PaxDbiQ8WY54.
    PRIDEiQ8WY54.

    PTM databases

    PhosphoSiteiQ8WY54.

    Expressioni

    Gene expression databases

    ArrayExpressiQ8WY54.
    BgeeiQ8WY54.
    CleanExiHS_PPM1E.
    GenevestigatoriQ8WY54.

    Organism-specific databases

    HPAiHPA018462.
    HPA019263.

    Interactioni

    Subunit structurei

    Heterotrimer. Interacts with PAX1 and ARHGEF6 (or ARHGEF7).1 Publication

    Protein-protein interaction databases

    BioGridi116515. 3 interactions.
    IntActiQ8WY54. 2 interactions.
    MINTiMINT-2812827.
    STRINGi9606.ENSP00000312411.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8WY54.
    SMRiQ8WY54. Positions 245-498.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati31 – 3221
    Repeati33 – 3422
    Repeati35 – 3623
    Repeati37 – 3824
    Repeati39 – 4025
    Repeati41 – 4226
    Repeati43 – 4427
    Repeati45 – 4628; approximate
    Repeati47 – 4829
    Repeati49 – 50210
    Repeati51 – 52211
    Domaini255 – 497243PP2C-likeAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni31 – 522211 X 2 AA tandem repeats of P-EAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi7 – 10094Glu-richAdd
    BLAST
    Compositional biasi31 – 139109Pro-richAdd
    BLAST

    Sequence similaritiesi

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

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiCOG0631.
    HOGENOMiHOG000059266.
    HOVERGENiHBG098260.
    InParanoidiQ8WY54.
    KOiK17501.
    OMAiPVEMFGP.
    OrthoDBiEOG7D2FDH.
    PhylomeDBiQ8WY54.
    TreeFamiTF317617.

    Family and domain databases

    Gene3Di3.60.40.10. 1 hit.
    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]
    SMARTiSM00331. PP2C_SIG. 1 hit.
    SM00332. PP2Cc. 1 hit.
    [Graphical view]
    SUPFAMiSSF81606. SSF81606. 1 hit.
    PROSITEiPS01032. PP2C. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8WY54-1) [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

    MAGCIPEEKT YRRFLELFLG EFRGPCGGGE PEPEPEPEPE PEPESEPEPE    50
    PELVEAEAAE ASVEEPGEEA ATVAATEEGD QEQDPEPEEE AAVEGEEEEE 100
    GAATAAAAPG HSAVPPPPPQ LPPLPPLPRP LSERITPRPL SERITREEVE 150
    GESLDLCLQQ LYKYNCPSFL AAALARATSD EVLQSDLSAH YIPKETDGTE 200
    GTVEIETVKL ARSVFSKLHE ICCSWVKDFP LRRRPQLYYE TSIHAIKNMR 250
    RKMEDKHVCI PDFNMLFNLE DQEEQAYFAV FDGHGGVDAA IYASIHLHVN 300
    LVRQEMFPHD PAEALCRAFR VTDERFVQKA ARESLRCGTT GVVTFIRGNM 350
    LHVAWVGDSQ VMLVRKGQAV ELMKPHKPDR EDEKQRIEAL GGCVVWFGAW 400
    RVNGSLSVSR AIGDAEHKPY ICGDADSAST VLDGTEDYLI LACDGFYDTV 450
    NPDEAVKVVS DHLKENNGDS SMVAHKLVAS ARDAGSSDNI TVIVVFLRDM 500
    NKAVNVSEES DWTENSFQGG QEDGGDDKEN HGECKRPWPQ HQCSAPADLG 550
    YDGRVDSFTD RTSLSPGSQI NVLEDPGYLD LTQIEASKPH SAQFLLPVEM 600
    FGPGAPKKAN LINELMMEKK SVQSSLPEWS GAGEFPTAFN LGSTGEQIYR 650
    MQSLSPVCSG LENEQFKSPG NRVSRLSHLR HHYSKKWHRF RFNPKFYSFL 700
    SAQEPSHKIG TSLSSLTGSG KRNRIRSSLP WRQNSWKGYS ENMRKLRKTH 750
    DIPCPDLPWS YKIE 764
    Length:764
    Mass (Da):85,002
    Last modified:November 2, 2010 - v2
    Checksum:i16F79EB84ED0E295
    GO
    Isoform 2 (identifier: Q8WY54-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         133-141: Missing.

    Show »
    Length:755
    Mass (Da):83,952
    Checksum:iC24C64A0A1BC1091
    GO
    Isoform 3 (identifier: Q8WY54-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         247-270: KNMRRKMEDKHVCIPDFNMLFNLE → MKSFRVIFLHIISQRKRMAQKGLW

    Note: No experimental confirmation available.

    Show »
    Length:764
    Mass (Da):84,967
    Checksum:i5B29325645AD2C48
    GO

    Sequence cautioni

    The sequence BAA83024.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti53 – 531L → P in DA497512. (PubMed:16344560)Curated
    Sequence conflicti394 – 3941V → I in AAF70325. 1 PublicationCurated

    Polymorphismi

    The poly-Pro-Glu stretch is polymorphic.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti44 – 441E → EPE.3 Publications
    VAR_063769
    Natural varianti231 – 2311L → S in a breast cancer sample; somatic mutation. 1 Publication
    VAR_036518
    Natural varianti320 – 3201R → G in a breast cancer sample; somatic mutation. 1 Publication
    VAR_036519

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei133 – 1419Missing in isoform 2. 2 PublicationsVSP_025197
    Alternative sequencei247 – 27024KNMRR…LFNLE → MKSFRVIFLHIISQRKRMAQ KGLW in isoform 3. 1 PublicationVSP_025198Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF520614 mRNA. Translation: AAM76058.1.
    AF260269 mRNA. Translation: AAF70325.1.
    AB028995 mRNA. Translation: BAA83024.2. Different initiation.
    CR749253 mRNA. Translation: CAH18109.1.
    AC025521 Genomic DNA. No translation available.
    AC100832 Genomic DNA. No translation available.
    DA497512 mRNA. No translation available.
    DA791319 mRNA. No translation available.
    CCDSiCCDS11613.1. [Q8WY54-2]
    RefSeqiXP_005257226.1. XM_005257169.2.
    UniGeneiHs.245044.

    Genome annotation databases

    EnsembliENST00000308249; ENSP00000312411; ENSG00000175175. [Q8WY54-2]
    GeneIDi22843.
    KEGGihsa:22843.
    UCSCiuc002iwx.4. human. [Q8WY54-2]
    uc010ddd.4. human. [Q8WY54-3]

    Polymorphism databases

    DMDMi311033412.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF520614 mRNA. Translation: AAM76058.1 .
    AF260269 mRNA. Translation: AAF70325.1 .
    AB028995 mRNA. Translation: BAA83024.2 . Different initiation.
    CR749253 mRNA. Translation: CAH18109.1 .
    AC025521 Genomic DNA. No translation available.
    AC100832 Genomic DNA. No translation available.
    DA497512 mRNA. No translation available.
    DA791319 mRNA. No translation available.
    CCDSi CCDS11613.1. [Q8WY54-2 ]
    RefSeqi XP_005257226.1. XM_005257169.2.
    UniGenei Hs.245044.

    3D structure databases

    ProteinModelPortali Q8WY54.
    SMRi Q8WY54. Positions 245-498.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 116515. 3 interactions.
    IntActi Q8WY54. 2 interactions.
    MINTi MINT-2812827.
    STRINGi 9606.ENSP00000312411.

    PTM databases

    PhosphoSitei Q8WY54.

    Polymorphism databases

    DMDMi 311033412.

    Proteomic databases

    MaxQBi Q8WY54.
    PaxDbi Q8WY54.
    PRIDEi Q8WY54.

    Protocols and materials databases

    DNASUi 22843.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000308249 ; ENSP00000312411 ; ENSG00000175175 . [Q8WY54-2 ]
    GeneIDi 22843.
    KEGGi hsa:22843.
    UCSCi uc002iwx.4. human. [Q8WY54-2 ]
    uc010ddd.4. human. [Q8WY54-3 ]

    Organism-specific databases

    CTDi 22843.
    GeneCardsi GC17P056833.
    H-InvDB HIX0014038.
    HGNCi HGNC:19322. PPM1E.
    HPAi HPA018462.
    HPA019263.
    neXtProti NX_Q8WY54.
    PharmGKBi PA134943567.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0631.
    HOGENOMi HOG000059266.
    HOVERGENi HBG098260.
    InParanoidi Q8WY54.
    KOi K17501.
    OMAi PVEMFGP.
    OrthoDBi EOG7D2FDH.
    PhylomeDBi Q8WY54.
    TreeFami TF317617.

    Miscellaneous databases

    ChiTaRSi PPM1E. human.
    GenomeRNAii 22843.
    NextBioi 13643771.
    PROi Q8WY54.

    Gene expression databases

    ArrayExpressi Q8WY54.
    Bgeei Q8WY54.
    CleanExi HS_PPM1E.
    Genevestigatori Q8WY54.

    Family and domain databases

    Gene3Di 3.60.40.10. 1 hit.
    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 SM00331. PP2C_SIG. 1 hit.
    SM00332. PP2Cc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF81606. SSF81606. 1 hit.
    PROSITEi PS01032. PP2C. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family."
      Koh C.-G., Tan E.-J., Manser E., Lim L.
      Curr. Biol. 12:317-321(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH ARHGEF, VARIANT PRO-GLU-44 INS.
    2. "Five novel genes from 17q23 amplicon have different amplification and overexpression frequency in breast cancer."
      Wu G., Couch F.J.
      Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT PRO-GLU-44 INS.
    3. "Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
      Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
      DNA Res. 6:197-205(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT PRO-GLU-44 INS.
      Tissue: Brain.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
      Tissue: Testis.
    5. "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].
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-112.
    7. "Identification and characterization of nuclear localization signals of CaMKP-N."
      Takeuchi M., Taniguchi T., Fujisawa H.
      J. Biochem. 136:183-188(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    8. "Post-translational excision of the carboxyl-terminal segment of CaM kinase phosphatase N and its cytosolic occurrence in the brain."
      Kitani T., Okuno S., Nakamura Y., Tokuno H., Takeuchi M., Fujisawa H.
      J. Neurochem. 96:374-384(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    9. Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-231 AND GLY-320.

    Entry informationi

    Entry nameiPPM1E_HUMAN
    AccessioniPrimary (citable) accession number: Q8WY54
    Secondary accession number(s): Q68DW1, Q7LAF3, Q9UPT0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 15, 2007
    Last sequence update: November 2, 2010
    Last modified: October 1, 2014
    This is version 97 of the entry and version 2 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3