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P49443

- PPM1A_MOUSE

UniProt

P49443 - PPM1A_MOUSE

Protein

Protein phosphatase 1A

Gene

Ppm1a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 121 (01 Oct 2014)
      Sequence version 1 (01 Feb 1996)
      Previous versions | rss
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    Functioni

    Enzyme with a broad specificity. Negatively regulates TGF-beta signaling through dephosphorylating SMAD2 and SMAD3, resulting in their dissociation from SMAD4, nuclear export of the SMADs and termination of the TGF-beta-mediated signaling By similarity. Dephosphorylates PRKAA1 and PRKAA2. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB.By similarity1 Publication

    Catalytic activityi

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

    Cofactori

    Binds 2 magnesium or manganese ions per subunit.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi60 – 601Manganese 1By similarity
    Metal bindingi60 – 601Manganese 2By similarity
    Metal bindingi61 – 611Manganese 1; via carbonyl oxygenBy similarity
    Metal bindingi239 – 2391Manganese 2By similarity
    Metal bindingi282 – 2821Manganese 2By similarity

    GO - Molecular functioni

    1. calmodulin-dependent protein phosphatase activity Source: Ensembl
    2. magnesium ion binding Source: InterPro
    3. manganese ion binding Source: InterPro
    4. phosphoprotein phosphatase activity Source: MGI
    5. R-SMAD binding Source: UniProtKB
    6. signal transducer activity Source: Ensembl

    GO - Biological processi

    1. negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
    2. negative regulation of NF-kappaB import into nucleus Source: UniProtKB
    3. negative regulation of SMAD protein complex assembly Source: Ensembl
    4. negative regulation of transforming growth factor beta receptor signaling pathway Source: Ensembl
    5. N-terminal protein myristoylation Source: UniProtKB
    6. peptidyl-threonine dephosphorylation Source: Ensembl
    7. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
    8. positive regulation of transcription, DNA-templated Source: Ensembl
    9. positive regulation of Wnt signaling pathway Source: Ensembl
    10. protein dephosphorylation Source: UniProtKB
    11. Wnt signaling pathway Source: Ensembl

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Keywords - Ligandi

    Magnesium, Manganese, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_220566. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
    REACT_220701. Regulation of AMPK activity via LKB1.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein phosphatase 1A (EC:3.1.3.16)
    Alternative name(s):
    Protein phosphatase 2C isoform alpha
    Short name:
    PP2C-alpha
    Protein phosphatase IA
    Gene namesi
    Name:Ppm1a
    Synonyms:Pppm1a
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 12

    Organism-specific databases

    MGIiMGI:99878. Ppm1a.

    Subcellular locationi

    Nucleus By similarity. Cytoplasmcytosol. Membrane
    Note: Weakly associates at the membrane and N-myristoylation mediates the membrane localization.

    GO - Cellular componenti

    1. cytosol Source: UniProtKB
    2. membrane Source: UniProtKB
    3. neuron projection Source: Ensembl
    4. nucleus Source: UniProtKB-SubCell
    5. voltage-gated calcium channel complex Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 382381Protein phosphatase 1APRO_0000057742Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi2 – 21N-myristoyl glycine1 Publication
    Modified residuei375 – 3751PhosphoserineBy similarity

    Post-translational modificationi

    N-myristoylation is essential for the recognition of its substrates for dephosphorylation.1 Publication

    Keywords - PTMi

    Lipoprotein, Myristate, Phosphoprotein

    Proteomic databases

    MaxQBiP49443.
    PaxDbiP49443.
    PRIDEiP49443.

    PTM databases

    PhosphoSiteiP49443.

    Expressioni

    Gene expression databases

    BgeeiP49443.
    GenevestigatoriP49443.

    Interactioni

    Subunit structurei

    Monomer By similarity. Interacts with SMAD2; the interaction dephosphorylates SMAD2 in its C-terminal SXS motif resulting in disruption of the SMAD2/SMAD4 complex, SMAD2 nuclear export and termination of the TGF-beta-mediated signaling. Interacts with SMAD2; the interaction dephosphorylates SMAD2 in its C-terminal SXS motif resulting in disruption of the SMAD2/SMAD4 complex, SMAD2 nuclear export and termination of the TGF-beta-mediated signaling By similarity. Interacts with the phosphorylated form of IKBKB/IKKB By similarity.By similarity

    Protein-protein interaction databases

    BioGridi202332. 3 interactions.
    IntActiP49443. 2 interactions.
    MINTiMINT-4108351.

    Structurei

    3D structure databases

    ProteinModelPortaliP49443.
    SMRiP49443. Positions 2-368.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the PP2C family.Curated

    Phylogenomic databases

    eggNOGiCOG0631.
    GeneTreeiENSGT00740000115384.
    HOGENOMiHOG000233895.
    HOVERGENiHBG053647.
    InParanoidiP49443.
    KOiK04457.
    OMAiEVYAIER.
    OrthoDBiEOG7WMCJH.
    PhylomeDBiP49443.
    TreeFamiTF313590.

    Family and domain databases

    Gene3Di1.10.10.430. 1 hit.
    3.60.40.10. 1 hit.
    InterProiIPR001932. PP2C-like_dom.
    IPR012911. PP2C_C.
    IPR000222. PP2C_Mn2_Asp60_BS.
    IPR015655. Protein_Pase_2C.
    [Graphical view]
    PANTHERiPTHR13832. PTHR13832. 1 hit.
    PfamiPF00481. PP2C. 1 hit.
    PF07830. PP2C_C. 1 hit.
    [Graphical view]
    SMARTiSM00331. PP2C_SIG. 1 hit.
    SM00332. PP2Cc. 1 hit.
    [Graphical view]
    SUPFAMiSSF81601. SSF81601. 1 hit.
    SSF81606. SSF81606. 1 hit.
    PROSITEiPS01032. PP2C. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P49443-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGAFLDKPKM EKHNAQGQGN GLRYGLSSMQ GWRVEMEDAH TAVIGLPSGL    50
    ETWSFFAVYD GHAGSQVAKY CCEHLLDHIT NNQDFRGSAG APSVENVKNG 100
    IRTGFLEIDE HMRVMSEKKH GADRSGSTAV GVLISPQHTY FINCGDSRGL 150
    LCRNRKVHFF TQDHKPSNPL EKERIQNAGG SVMIQRVNGS LAVSRALGDF 200
    DYKCVHGKGP TEQLVSPEPE VHDIERSEED DQFIILACDG IWDVMGNEEL 250
    CDFVRSRLEV TDDLEKVCNE VVDTCLYKGS RDNMSVILIC FPSAPKVSAE 300
    AVKKEAELDK YLESRVEEII KKQVEGVPDL VHVMRTLASE NIPSLPPGGE 350
    LASKRNVIEA VYNRLNPYKN DDTDSASTDD MW 382
    Length:382
    Mass (Da):42,433
    Last modified:February 1, 1996 - v1
    Checksum:iDC206610E1583870
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D28117 mRNA. Translation: BAA05662.1.
    BC008595 mRNA. Translation: AAH08595.1.
    CCDSiCCDS25970.1.
    PIRiI53823.
    RefSeqiNP_032936.1. NM_008910.3.
    XP_006515666.1. XM_006515603.1.
    UniGeneiMm.261045.

    Genome annotation databases

    EnsembliENSMUST00000021514; ENSMUSP00000021514; ENSMUSG00000021096.
    GeneIDi19042.
    KEGGimmu:19042.
    UCSCiuc007nvu.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D28117 mRNA. Translation: BAA05662.1 .
    BC008595 mRNA. Translation: AAH08595.1 .
    CCDSi CCDS25970.1.
    PIRi I53823.
    RefSeqi NP_032936.1. NM_008910.3.
    XP_006515666.1. XM_006515603.1.
    UniGenei Mm.261045.

    3D structure databases

    ProteinModelPortali P49443.
    SMRi P49443. Positions 2-368.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 202332. 3 interactions.
    IntActi P49443. 2 interactions.
    MINTi MINT-4108351.

    PTM databases

    PhosphoSitei P49443.

    Proteomic databases

    MaxQBi P49443.
    PaxDbi P49443.
    PRIDEi P49443.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000021514 ; ENSMUSP00000021514 ; ENSMUSG00000021096 .
    GeneIDi 19042.
    KEGGi mmu:19042.
    UCSCi uc007nvu.2. mouse.

    Organism-specific databases

    CTDi 5494.
    MGIi MGI:99878. Ppm1a.

    Phylogenomic databases

    eggNOGi COG0631.
    GeneTreei ENSGT00740000115384.
    HOGENOMi HOG000233895.
    HOVERGENi HBG053647.
    InParanoidi P49443.
    KOi K04457.
    OMAi EVYAIER.
    OrthoDBi EOG7WMCJH.
    PhylomeDBi P49443.
    TreeFami TF313590.

    Enzyme and pathway databases

    Reactomei REACT_220566. Downregulation of SMAD2/3:SMAD4 transcriptional activity.
    REACT_220701. Regulation of AMPK activity via LKB1.

    Miscellaneous databases

    ChiTaRSi PPM1A. mouse.
    NextBioi 295493.
    PROi P49443.
    SOURCEi Search...

    Gene expression databases

    Bgeei P49443.
    Genevestigatori P49443.

    Family and domain databases

    Gene3Di 1.10.10.430. 1 hit.
    3.60.40.10. 1 hit.
    InterProi IPR001932. PP2C-like_dom.
    IPR012911. PP2C_C.
    IPR000222. PP2C_Mn2_Asp60_BS.
    IPR015655. Protein_Pase_2C.
    [Graphical view ]
    PANTHERi PTHR13832. PTHR13832. 1 hit.
    Pfami PF00481. PP2C. 1 hit.
    PF07830. PP2C_C. 1 hit.
    [Graphical view ]
    SMARTi SM00331. PP2C_SIG. 1 hit.
    SM00332. PP2Cc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF81601. SSF81601. 1 hit.
    SSF81606. SSF81606. 1 hit.
    PROSITEi PS01032. PP2C. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The cDNA sequence encoding mouse Mg2+ -dependent protein phosphatase alpha."
      Kato S., Kobayashi T., Terasawa T., Ohnishi M., Sasahara Y., Kanamaru R., Tamura S.
      Gene 145:311-312(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Brain.
    2. "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].
      Strain: FVB/N.
      Tissue: Mammary gland.
    3. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    4. "Protein phosphatase 5 modulates SMAD3 function in the transforming growth factor-? pathway."
      Bruce D.L., Macartney T., Yong W., Shou W., Sapkota G.P.
      Cell. Signal. 24:1999-2006(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    5. "N-Myristoylation is essential for protein phosphatases PPM1A and PPM1B to dephosphorylate their physiological substrates in cells."
      Chida T., Ando M., Matsuki T., Masu Y., Nagaura Y., Takano-Yamamoto T., Tamura S., Kobayashi T.
      Biochem. J. 449:741-749(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, MYRISTOYLATION AT GLY-2.

    Entry informationi

    Entry nameiPPM1A_MOUSE
    AccessioniPrimary (citable) accession number: P49443
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: February 1, 1996
    Last modified: October 1, 2014
    This is version 121 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3