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P60510 (PP4C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein phosphatase 4 catalytic subunit

Short name=PP4C
Short name=Pp4
EC=3.1.3.16
Alternative name(s):
Protein phosphatase X
Short name=PP-X
Gene names
Name:PPP4C
Synonyms:PPP4, PPX
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length307 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.5 Ref.6 Ref.7 Ref.9 Ref.11 Ref.12 Ref.14 Ref.15 Ref.17

Catalytic activity

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

Cofactor

Binds 2 manganese ions per subunit By similarity.

Subunit structure

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. Ref.1 Ref.7 Ref.8 Ref.9 Ref.10 Ref.13 Ref.15

Subcellular location

Cytoplasm. Nucleus. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome.

Sequence similarities

Belongs to the PPP phosphatase family. PP-4 (PP-X) subfamily.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.16
Chain2 – 307306Serine/threonine-protein phosphatase 4 catalytic subunit
PRO_0000058883

Sites

Active site1151Proton donor By similarity
Metal binding541Manganese 1 By similarity
Metal binding561Manganese 1 By similarity
Metal binding821Manganese 1 By similarity
Metal binding821Manganese 2 By similarity
Metal binding1141Manganese 2 By similarity
Metal binding1641Manganese 2 By similarity
Metal binding2381Manganese 2 By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.16 Ref.19 Ref.20
Modified residue3071Leucine methyl ester By similarity

Experimental info

Mutagenesis391E → K: Diminishes interaction with PPP4R4. Ref.13
Mutagenesis641E → K: Abolishes interaction with PPP4R4. Ref.13
Mutagenesis761N → D: Diminishes interaction with PPP4R4. Ref.13
Mutagenesis821D → A: Loss of activity. Ref.17
Mutagenesis1071R → E: Diminishes interaction with PPP4R4. Ref.13
Mutagenesis2771E → K: Abolishes interaction with PPP4R4; no effect on interaction with PPP4R1 and PPP4R2. Ref.13

Sequences

Sequence LengthMass (Da)Tools
P60510 [UniParc].

Last modified March 1, 2004. Version 1.
Checksum: D6FE470A5C6CBCAC

FASTA30735,080
        10         20         30         40         50         60 
MAEISDLDRQ IEQLRRCELI KESEVKALCA KAREILVEES NVQRVDSPVT VCGDIHGQFY 

        70         80         90        100        110        120 
DLKELFRVGG DVPETNYLFM GDFVDRGFYS VETFLLLLAL KVRYPDRITL IRGNHESRQI 

       130        140        150        160        170        180 
TQVYGFYDEC LRKYGSVTVW RYCTEIFDYL SLSAIIDGKI FCVHGGLSPS IQTLDQIRTI 

       190        200        210        220        230        240 
DRKQEVPHDG PMCDLLWSDP EDTTGWGVSP RGAGYLFGSD VVAQFNAAND IDMICRAHQL 

       250        260        270        280        290        300 
VMEGYKWHFN ETVLTVWSAP NYCYRCGNVA AILELDEHLQ KDFIIFEAAP QETRGIPSKK 


PVADYFL 

« Hide

References

« Hide 'large scale' references
[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]"Functional expression cloning reveals proapoptotic role for protein phosphatase 4."
Mourtada-Maarabouni M., Kirkham L., Jenkins B., Rayner J., Gonda T.J., Starr R., Trayner I., Farzaneh F., Williams G.T.
Cell Death Differ. 10:1016-1024(2003) [PubMed] [Europe PMC] [Abstract]
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X70218 mRNA. Translation: CAA49753.1.
AF097996 mRNA. Translation: AAC96318.1.
BC001416 mRNA. Translation: AAH01416.1.
CCDSCCDS10669.1.
PIRS28173.
RefSeqNP_002711.1. NM_002720.1.
XP_005255475.1. XM_005255418.2.
UniGeneHs.534338.

3D structure databases

ProteinModelPortalP60510.
SMRP60510. Positions 6-291.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111523. 54 interactions.
IntActP60510. 26 interactions.
MINTMINT-5004373.
STRING9606.ENSP00000279387.

PTM databases

PhosphoSiteP60510.

Polymorphism databases

DMDM44888846.

Proteomic databases

MaxQBP60510.
PaxDbP60510.
PeptideAtlasP60510.
PRIDEP60510.

Protocols and materials databases

DNASU5531.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000279387; ENSP00000279387; ENSG00000149923.
ENST00000561610; ENSP00000455995; ENSG00000149923.
GeneID5531.
KEGGhsa:5531.
UCSCuc002dwe.3. human.

Organism-specific databases

CTD5531.
GeneCardsGC16P030087.
HGNCHGNC:9319. PPP4C.
HPAHPA043837.
MIM602035. gene.
neXtProtNX_P60510.
PharmGKBPA33683.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0639.
HOGENOMHOG000172696.
HOVERGENHBG000216.
InParanoidP60510.
KOK15423.
OMAVFNHRND.
OrthoDBEOG74N5H2.
PhylomeDBP60510.
TreeFamTF105559.

Enzyme and pathway databases

SignaLinkP60510.

Gene expression databases

ArrayExpressP60510.
BgeeP60510.
CleanExHS_PPP4C.
GenevestigatorP60510.

Family and domain databases

Gene3D3.60.21.10. 1 hit.
InterProIPR004843. Calcineurin-like_PHP_apaH.
IPR029052. Metallo-depent_PP-like.
IPR006186. Ser/Thr-sp_prot-phosphatase.
[Graphical view]
PfamPF00149. Metallophos. 1 hit.
[Graphical view]
PRINTSPR00114. STPHPHTASE.
SMARTSM00156. PP2Ac. 1 hit.
[Graphical view]
SUPFAMSSF56300. SSF56300. 1 hit.
PROSITEPS00125. SER_THR_PHOSPHATASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPPP4C.
GenomeRNAi5531.
NextBio21426.
PROP60510.
SOURCESearch...

Entry information

Entry namePP4C_HUMAN
AccessionPrimary (citable) accession number: P60510
Secondary accession number(s): P33172
Entry history
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2004
Last modified: July 9, 2014
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM