P60510 (PP4C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	307 AA.
Sequence status	Complete.
Protein existence	Evidence 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.16
Catalytic activity	A phosphoprotein + H2O = a protein + phosphate.
Cofactor	Binds 1 iron ion per subunit By similarity. Binds 1 manganese ion 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. Cytoplasm › cytoskeleton › centrosome.
Sequence similarities	Belongs to the PPP phosphatase family. PP-4 (PP-X) subfamily.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton Nucleus
Ligand	Iron Manganese Metal-binding
Molecular function	Hydrolase Protein phosphatase
PTM	Methylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	microtubule cytoskeleton organization Non-traceable author statement. Source: UniProtKB regulation of double-strand break repair via homologous recombination Inferred from mutant phenotype Ref.16. Source: UniProtKB
Cellular_component	centrosome Non-traceable author statement. Source: UniProtKB cytoplasm Inferred from direct assay. Source: HPA nucleus Non-traceable author statement. Source: UniProtKB plasma membrane Inferred from direct assay. Source: HPA protein phosphatase 4 complex Inferred from electronic annotation. Source: Compara
Molecular_function	NF-kappaB-inducing kinase activity Non-traceable author statement Ref.3. Source: UniProtKB metal ion binding Non-traceable author statement. Source: UniProtKB protein serine/threonine phosphatase activity Inferred from direct assay Ref.16. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IGBP1	P78318	7	EBI-1046072,EBI-1055954
PPP2R1A	P30153	3	EBI-1046072,EBI-302388
PPP4R1	Q8TF05	5	EBI-1046072,EBI-1056262
PPP4R2	Q9NY27	8	EBI-1046072,EBI-1048740
PPP4R4	Q6NUP7	6	EBI-1046072,EBI-1774189
TIPRL	O75663	2	EBI-1046072,EBI-1054735

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 307	307	Serine/threonine-protein phosphatase 4 catalytic subunit		PRO_0000058883
Sites
	Active site	115	1	Proton donor By similarity
	Metal binding	54	1	Iron By similarity
	Metal binding	56	1	Iron By similarity
	Metal binding	82	1	Iron By similarity
	Metal binding	82	1	Manganese By similarity
	Metal binding	114	1	Manganese By similarity
	Metal binding	164	1	Manganese By similarity
	Metal binding	238	1	Manganese By similarity
Amino acid modifications
	Modified residue	307	1	Leucine methyl ester By similarity
Experimental info
	Mutagenesis	39	1	E → K: Diminishes interaction with PPP4R4. Ref.13
	Mutagenesis	64	1	E → K: Abolishes interaction with PPP4R4. Ref.13
	Mutagenesis	76	1	N → D: Diminishes interaction with PPP4R4. Ref.13
	Mutagenesis	82	1	D → A: Loss of activity. Ref.16
	Mutagenesis	107	1	R → E: Diminishes interaction with PPP4R4. Ref.13
	Mutagenesis	277	1	E → K: Abolishes interaction with PPP4R4; no effect on interaction with PPP4R1 and PPP4R2. Ref.13

Sequences

	Sequence		Length	Mass (Da)
	P60510 [UniParc]. Last modified March 1, 2004. Version 1. Checksum: D6FE470A5C6CBCAC	FASTA	307	35,080
	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

References

	« Hide 'large scale' referencesShow '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, 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]	"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.
[17]	"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].

Cross-references

Sequence databases
EMBL GenBank DDBJ	X70218 mRNA. Translation: CAA49753.1. AF097996 mRNA. Translation: AAC96318.1. BC001416 mRNA. Translation: AAH01416.1.
IPI	IPI00012833.
PIR	S28173.
RefSeq	NP_002711.1. NM_002720.1.
UniGene	Hs.534338.
3D structure databases
ProteinModelPortal	P60510.
ModBase	Search...
Protein-protein interaction databases
IntAct	P60510. 22 interactions.
STRING	9606.ENSP00000279387.
PTM databases
PhosphoSite	P60510.
Polymorphism databases
DMDM	44888846.
Proteomic databases
PaxDb	P60510.
PeptideAtlas	P60510.
PRIDE	P60510.
Protocols and materials databases
DNASU	5531.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000279387; ENSP00000279387; ENSG00000149923. ENST00000561610; ENSP00000455995; ENSG00000149923.
GeneID	5531.
KEGG	hsa:5531.
UCSC	uc002dwe.3. human.
Organism-specific databases
CTD	5531.
GeneCards	GC16P030087.
HGNC	HGNC:9319. PPP4C.
HPA	HPA043837.
MIM	602035. gene.
neXtProt	NX_P60510.
PharmGKB	PA33683.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0639.
HOGENOM	HOG000172696.
HOVERGEN	HBG000216.
InParanoid	P60510.
KO	K15423.
OMA	GFKWHFN.
OrthoDB	EOG4NS3BV.
PhylomeDB	P60510.
Gene expression databases
ArrayExpress	P60510.
Bgee	P60510.
CleanEx	HS_PPP4C.
Genevestigator	P60510.
GermOnline	ENSG00000149923. Homo sapiens.
Family and domain databases
InterPro	IPR004843. Metallo_PEstase_dom. IPR006186. Ser/Thr-sp_prot-phosphatase. [Graphical view]
Pfam	PF00149. Metallophos. 1 hit. [Graphical view]
PRINTS	PR00114. STPHPHTASE.
SMART	SM00156. PP2Ac. 1 hit. [Graphical view]
PROSITE	PS00125. SER_THR_PHOSPHATASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	5531.
NextBio	21426.
SOURCE	Search...

Entry information

Entry name

PP4C_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.