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P60510

- PP4C_HUMAN

UniProt

P60510 - PP4C_HUMAN

Protein

Serine/threonine-protein phosphatase 4 catalytic subunit

Gene

PPP4C

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 111 (01 Oct 2014)
      Sequence version 1 (01 Mar 2004)
      Previous versions | rss
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    Functioni

    Protein phosphatase that is involved in many processes such as microtubule organization at centrosomes, maturation of spliceosomal snRNPs, apoptosis, DNA repair, tumor necrosis factor (TNF)-alpha signaling, activation of c-Jun N-terminal kinase MAPK8, regulation of histone acetylation, DNA damage checkpoint signaling, NF-kappa-B activation and cell migration. The PPP4C-PPP4R1 PP4 complex may play a role in dephosphorylation and regulation of HDAC3. The PPP4C-PPP4R2-PPP4R3A PP4 complex specifically dephosphorylates H2AFX phosphorylated on Ser-140 (gamma-H2AFX) generated during DNA replication and required for DNA double strand break repair. Dephosphorylates NDEL1 at CDK1 phosphorylation sites and negatively regulates CDK1 activity in interphase By similarity. In response to DNA damage, catalyzes RPA2 dephosphorylation, an essential step for DNA repair since it allows the efficient RPA2-mediated recruitment of RAD51 to chromatin.By similarity10 Publications

    Catalytic activityi

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

    Cofactori

    Binds 2 manganese ions per subunit.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi54 – 541Manganese 1By similarity
    Metal bindingi56 – 561Manganese 1By similarity
    Metal bindingi82 – 821Manganese 1By similarity
    Metal bindingi82 – 821Manganese 2By similarity
    Metal bindingi114 – 1141Manganese 2By similarity
    Active sitei115 – 1151Proton donorBy similarity
    Metal bindingi164 – 1641Manganese 2By similarity
    Metal bindingi238 – 2381Manganese 2By similarity

    GO - Molecular functioni

    1. metal ion binding Source: UniProtKB-KW
    2. NF-kappaB-inducing kinase activity Source: UniProtKB
    3. protein binding Source: UniProtKB
    4. protein serine/threonine phosphatase activity Source: UniProtKB

    GO - Biological processi

    1. dephosphorylation Source: GOC
    2. NIK/NF-kappaB signaling Source: GOC
    3. regulation of double-strand break repair via homologous recombination Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Keywords - Ligandi

    Manganese, Metal-binding

    Enzyme and pathway databases

    SignaLinkiP60510.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serine/threonine-protein phosphatase 4 catalytic subunit (EC:3.1.3.16)
    Short name:
    PP4C
    Short name:
    Pp4
    Alternative name(s):
    Protein phosphatase X
    Short name:
    PP-X
    Gene namesi
    Name:PPP4C
    Synonyms:PPP4, PPX
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:9319. PPP4C.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: HPA
    2. microtubule organizing center Source: UniProtKB-SubCell
    3. nucleus Source: HPA
    4. plasma membrane Source: HPA
    5. protein phosphatase 4 complex Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm, Cytoskeleton, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi39 – 391E → K: Diminishes interaction with PPP4R4. 1 Publication
    Mutagenesisi64 – 641E → K: Abolishes interaction with PPP4R4. 1 Publication
    Mutagenesisi76 – 761N → D: Diminishes interaction with PPP4R4. 1 Publication
    Mutagenesisi82 – 821D → A: Loss of activity. 1 Publication
    Mutagenesisi107 – 1071R → E: Diminishes interaction with PPP4R4. 1 Publication
    Mutagenesisi277 – 2771E → K: Abolishes interaction with PPP4R4; no effect on interaction with PPP4R1 and PPP4R2. 1 Publication

    Organism-specific databases

    PharmGKBiPA33683.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed3 Publications
    Chaini2 – 307306Serine/threonine-protein phosphatase 4 catalytic subunitPRO_0000058883Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine3 Publications
    Modified residuei307 – 3071Leucine methyl esterBy similarity

    Keywords - PTMi

    Acetylation, Methylation

    Proteomic databases

    MaxQBiP60510.
    PaxDbiP60510.
    PeptideAtlasiP60510.
    PRIDEiP60510.

    PTM databases

    PhosphoSiteiP60510.

    Expressioni

    Gene expression databases

    ArrayExpressiP60510.
    BgeeiP60510.
    CleanExiHS_PPP4C.
    GenevestigatoriP60510.

    Organism-specific databases

    HPAiHPA043837.

    Interactioni

    Subunit structurei

    Serine/threonine-protein phosphatase 4 (PP4) occurs in different assemblies of the catalytic and one or more regulatory subunits. Component of the PP4 complexes PPP4C-PPP4R1, PPP4C-PPP4R2, PPP4C-PPP4R2-PPP4R3A, PPP4C-PPP4R2-PPP4R3B and PPP4C-PPP4R4. The PPP4C-PPP4R2 complex appears to be a tetramer composed of 2 molecules of PPP4C and 2 molecules of PPP4R2. Interacts with REL, NFKB1/p50 and RELA. Interacts with SMN1 AND GEMIN4. Interacts with IRS4 (phosphorylated). Interacts with SMEK1/PPP4R3A; the interaction requires PP4R2. Interacts with HDAC3.7 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    HDAC3O153794EBI-1046072,EBI-607682
    IGBP1P783187EBI-1046072,EBI-1055954
    PPP2R1AP301533EBI-1046072,EBI-302388
    PPP4R1Q8TF055EBI-1046072,EBI-1056262
    PPP4R2Q9NY278EBI-1046072,EBI-1048740
    PPP4R4Q6NUP76EBI-1046072,EBI-1774189
    TIPRLO756633EBI-1046072,EBI-1054735

    Protein-protein interaction databases

    BioGridi111523. 54 interactions.
    IntActiP60510. 26 interactions.
    MINTiMINT-5004373.
    STRINGi9606.ENSP00000279387.

    Structurei

    3D structure databases

    ProteinModelPortaliP60510.
    SMRiP60510. Positions 6-291.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiCOG0639.
    HOGENOMiHOG000172696.
    HOVERGENiHBG000216.
    InParanoidiP60510.
    KOiK15423.
    OMAiVFNHRND.
    OrthoDBiEOG74N5H2.
    PhylomeDBiP60510.
    TreeFamiTF105559.

    Family and domain databases

    Gene3Di3.60.21.10. 1 hit.
    InterProiIPR004843. Calcineurin-like_PHP_apaH.
    IPR029052. Metallo-depent_PP-like.
    IPR006186. Ser/Thr-sp_prot-phosphatase.
    [Graphical view]
    PfamiPF00149. Metallophos. 1 hit.
    [Graphical view]
    PRINTSiPR00114. STPHPHTASE.
    SMARTiSM00156. PP2Ac. 1 hit.
    [Graphical view]
    SUPFAMiSSF56300. SSF56300. 1 hit.
    PROSITEiPS00125. SER_THR_PHOSPHATASE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P60510-1 [UniParc]FASTAAdd to Basket

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    MAEISDLDRQ IEQLRRCELI KESEVKALCA KAREILVEES NVQRVDSPVT    50
    VCGDIHGQFY DLKELFRVGG DVPETNYLFM GDFVDRGFYS VETFLLLLAL 100
    KVRYPDRITL IRGNHESRQI TQVYGFYDEC LRKYGSVTVW RYCTEIFDYL 150
    SLSAIIDGKI FCVHGGLSPS IQTLDQIRTI DRKQEVPHDG PMCDLLWSDP 200
    EDTTGWGVSP RGAGYLFGSD VVAQFNAAND IDMICRAHQL VMEGYKWHFN 250
    ETVLTVWSAP NYCYRCGNVA AILELDEHLQ KDFIIFEAAP QETRGIPSKK 300
    PVADYFL 307
    Length:307
    Mass (Da):35,080
    Last modified:March 1, 2004 - v1
    Checksum:iD6FE470A5C6CBCAC
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X70218 mRNA. Translation: CAA49753.1.
    AF097996 mRNA. Translation: AAC96318.1.
    BC001416 mRNA. Translation: AAH01416.1.
    CCDSiCCDS10669.1.
    PIRiS28173.
    RefSeqiNP_002711.1. NM_002720.1.
    XP_005255475.1. XM_005255418.2.
    UniGeneiHs.534338.

    Genome annotation databases

    EnsembliENST00000279387; ENSP00000279387; ENSG00000149923.
    ENST00000561610; ENSP00000455995; ENSG00000149923.
    GeneIDi5531.
    KEGGihsa:5531.
    UCSCiuc002dwe.3. human.

    Polymorphism databases

    DMDMi44888846.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X70218 mRNA. Translation: CAA49753.1 .
    AF097996 mRNA. Translation: AAC96318.1 .
    BC001416 mRNA. Translation: AAH01416.1 .
    CCDSi CCDS10669.1.
    PIRi S28173.
    RefSeqi NP_002711.1. NM_002720.1.
    XP_005255475.1. XM_005255418.2.
    UniGenei Hs.534338.

    3D structure databases

    ProteinModelPortali P60510.
    SMRi P60510. Positions 6-291.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111523. 54 interactions.
    IntActi P60510. 26 interactions.
    MINTi MINT-5004373.
    STRINGi 9606.ENSP00000279387.

    PTM databases

    PhosphoSitei P60510.

    Polymorphism databases

    DMDMi 44888846.

    Proteomic databases

    MaxQBi P60510.
    PaxDbi P60510.
    PeptideAtlasi P60510.
    PRIDEi P60510.

    Protocols and materials databases

    DNASUi 5531.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000279387 ; ENSP00000279387 ; ENSG00000149923 .
    ENST00000561610 ; ENSP00000455995 ; ENSG00000149923 .
    GeneIDi 5531.
    KEGGi hsa:5531.
    UCSCi uc002dwe.3. human.

    Organism-specific databases

    CTDi 5531.
    GeneCardsi GC16P030087.
    HGNCi HGNC:9319. PPP4C.
    HPAi HPA043837.
    MIMi 602035. gene.
    neXtProti NX_P60510.
    PharmGKBi PA33683.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0639.
    HOGENOMi HOG000172696.
    HOVERGENi HBG000216.
    InParanoidi P60510.
    KOi K15423.
    OMAi VFNHRND.
    OrthoDBi EOG74N5H2.
    PhylomeDBi P60510.
    TreeFami TF105559.

    Enzyme and pathway databases

    SignaLinki P60510.

    Miscellaneous databases

    GeneWikii PPP4C.
    GenomeRNAii 5531.
    NextBioi 21426.
    PROi P60510.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P60510.
    Bgeei P60510.
    CleanExi HS_PPP4C.
    Genevestigatori P60510.

    Family and domain databases

    Gene3Di 3.60.21.10. 1 hit.
    InterProi IPR004843. Calcineurin-like_PHP_apaH.
    IPR029052. Metallo-depent_PP-like.
    IPR006186. Ser/Thr-sp_prot-phosphatase.
    [Graphical view ]
    Pfami PF00149. Metallophos. 1 hit.
    [Graphical view ]
    PRINTSi PR00114. STPHPHTASE.
    SMARTi SM00156. PP2Ac. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56300. SSF56300. 1 hit.
    PROSITEi PS00125. SER_THR_PHOSPHATASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Protein phosphatase X has been highly conserved during mammalian evolution."
      Brewis N.D., Cohen P.T.W.
      Biochim. Biophys. Acta 1171:231-233(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH REL; NFKB1 AND RELA, FUNCTION.
    2. Cohen P.T.W.
      Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION TO 75.
    3. "Protein phosphatase X interacts with c-Rel and stimulates c-Rel/nuclear factor kappaB activity."
      Hu M.C.-T., Tang-Oxley Q., Qiu W.R., Wang Y.-P., Mihindukulasuriya K.A., Afshar R., Tan T.-H.
      J. Biol. Chem. 273:33561-33565(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "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].
      Tissue: Placenta.
    5. "Protein phosphatase 4 is involved in tumor necrosis factor-alpha-induced activation of c-Jun N-terminal kinase."
      Zhou G., Mihindukulasuriya K.A., MacCorkle-Chosnek R.A., Van Hooser A., Hu M.C., Brinkley B.R., Tan T.H.
      J. Biol. Chem. 277:6391-6398(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. Cited for: FUNCTION.
    7. "Protein phosphatase 4 interacts with the survival of motor neurons complex and enhances the temporal localisation of snRNPs."
      Carnegie G.K., Sleeman J.E., Morrice N., Hastie C.J., Peggie M.W., Philp A., Lamond A.I., Cohen P.T.W.
      J. Cell Sci. 116:1905-1913(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH PPP4R2; SMN1 AND GEMIN4, COMPOSITION OF THE PPP4C-PPP4R2 COMPLEX.
    8. "Protein phosphatase 4 interacts with and down-regulates insulin receptor substrate 4 following tumor necrosis factor-alpha stimulation."
      Mihindukulasuriya K.A., Zhou G., Qin J., Tan T.-H.
      J. Biol. Chem. 279:46588-46594(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH IRS4.
    9. "Histone deacetylase 3 (HDAC3) activity is regulated by interaction with protein serine/threonine phosphatase 4."
      Zhang X., Ozawa Y., Lee H., Wen Y.D., Tan T.H., Wadzinski B.E., Seto E.
      Genes Dev. 19:827-839(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HDAC3, FUNCTION OF THE PPP4C-PPP4R1 COMPLEX.
    10. "A novel, evolutionarily conserved protein phosphatase complex involved in cisplatin sensitivity."
      Gingras A.-C., Caballero M., Zarske M., Sanchez A., Hazbun T.R., Fields S., Sonenberg N., Hafen E., Raught B., Aebersold R.
      Mol. Cell. Proteomics 4:1725-1740(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN THE PPP4C-PPP4R2-PPP4R3A COMPLEX, INTERACTION WITH SMEK1, IDENTIFICATION BY MASS SPECTROMETRY.
    11. "PP4 is a gammaH2AX phosphatase required for recovery from the DNA damage checkpoint."
      Nakada S., Chen G.I., Gingras A.C., Durocher D.
      EMBO Rep. 9:1019-1026(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "Depletion of protein phosphatase 4 in human cells reveals essential roles in centrosome maturation, cell migration and the regulation of Rho GTPases."
      Martin-Granados C., Philp A., Oxenham S.K., Prescott A.R., Cohen P.T.W.
      Int. J. Biochem. Cell Biol. 40:2315-2332(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    13. "PP4R4/KIAA1622 forms a novel stable cytosolic complex with phosphoprotein phosphatase 4."
      Chen G.I., Tisayakorn S., Jorgensen C., D'Ambrosio L.M., Goudreault M., Gingras A.-C.
      J. Biol. Chem. 283:29273-29284(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PPP4R4, IDENTIFICATION IN THE PPP4C-PPP4R4 COMPLEX, MUTAGENESIS OF GLU-39; GLU-64; ASN-76; ARG-107 AND GLU-277.
    14. "Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1 dephosphorylation."
      Toyo-oka K., Mori D., Yano Y., Shiota M., Iwao H., Goto H., Inagaki M., Hiraiwa N., Muramatsu M., Wynshaw-Boris A., Yoshiki A., Hirotsune S.
      J. Cell Biol. 180:1133-1147(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    15. "A PP4-phosphatase complex dephosphorylates gamma-H2AX generated during DNA replication."
      Chowdhury D., Xu X., Zhong X., Ahmed F., Zhong J., Liao J., Dykxhoorn D.M., Weinstock D.M., Pfeifer G.P., Lieberman J.
      Mol. Cell 31:33-46(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN THE PPP4C-PPP4R1 COMPLEX, IDENTIFICATION IN THE PPP4C-PPP4R2-PPP4R3A COMPLEX, IDENTIFICATION IN THE PPP4C-PPP4R2-PPP4R3B COMPLEX, FUNCTION OF THE PPP4C-PPP4R2-PPP4R3A COMPLEX.
    16. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
    17. "A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair via homologous recombination."
      Lee D.H., Pan Y., Kanner S., Sung P., Borowiec J.A., Chowdhury D.
      Nat. Struct. Mol. Biol. 17:365-372(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF ASP-82.
    18. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    19. "Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
      Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
      Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    20. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiPP4C_HUMAN
    AccessioniPrimary (citable) accession number: P60510
    Secondary accession number(s): P33172
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 1, 2004
    Last sequence update: March 1, 2004
    Last modified: October 1, 2014
    This is version 111 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 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3