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P60510

- PP4C_HUMAN

UniProt

P60510 - PP4C_HUMAN

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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

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 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
Complete GO annotation...

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. cytoskeleton Source: UniProtKB-KW
  3. nucleus Source: HPA
  4. plasma membrane Source: HPA
  5. protein phosphatase 4 complex Source: Ensembl
Complete GO annotation...

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

BgeeiP60510.
CleanExiHS_PPP4C.
ExpressionAtlasiP60510. baseline and differential.
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. 57 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.
GeneTreeiENSGT00550000074618.
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

« Hide

        10         20         30         40         50
MAEISDLDRQ IEQLRRCELI KESEVKALCA KAREILVEES NVQRVDSPVT
60 70 80 90 100
VCGDIHGQFY DLKELFRVGG DVPETNYLFM GDFVDRGFYS VETFLLLLAL
110 120 130 140 150
KVRYPDRITL IRGNHESRQI TQVYGFYDEC LRKYGSVTVW RYCTEIFDYL
160 170 180 190 200
SLSAIIDGKI FCVHGGLSPS IQTLDQIRTI DRKQEVPHDG PMCDLLWSDP
210 220 230 240 250
EDTTGWGVSP RGAGYLFGSD VVAQFNAAND IDMICRAHQL VMEGYKWHFN
260 270 280 290 300
ETVLTVWSAP NYCYRCGNVA AILELDEHLQ KDFIIFEAAP QETRGIPSKK

PVADYFL
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. 57 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.
GeneTreei ENSGT00550000074618.
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

Bgeei P60510.
CleanExi HS_PPP4C.
ExpressionAtlasi P60510. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 112 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