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Identification
HMDB Protein ID HMDBP08686
Secondary Accession Numbers
  • 14407
Name Serine/threonine-protein phosphatase 4 catalytic subunit
Synonyms
  1. PP-X
  2. PP4C
  3. Pp4
  4. Protein phosphatase X
Gene Name PPP4C
Protein Type Unknown
Biological Properties
General Function Involved in hydrolase activity
Specific 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.
Pathways Not Available
Reactions
A phosphoprotein + Water → a protein + Phosphate details
GO Classification
Biological Process
regulation of double-strand break repair via homologous recombination
microtubule cytoskeleton organization
Cellular Component
centrosome
cytoplasm
plasma membrane
nucleus
Function
catalytic activity
hydrolase activity
Molecular Function
protein serine/threonine phosphatase activity
metal ion binding
NF-kappaB-inducing kinase activity
Cellular Location
  1. Nucleus
  2. Cytoplasm
  3. Cytoplasm
  4. cytoskeleton
  5. centrosome
Gene Properties
Chromosome Location 16
Locus 16p11.2
SNPs PPP4C
Gene Sequence
>924 bp
ATGGCGGAGATCAGCGACCTGGACCGGCAGATCGAGCAGCTGCGTCGCTGCGAGCTCATC
AAGGAGAGCGAAGTCAAGGCCCTGTGCGCTAAGGCCAGAGAGATCTTGGTAGAGGAGAGC
AACGTGCAGAGGGTGGACTCGCCAGTCACAGTGTGCGGCGACATCCATGGACAATTCTAT
GACCTCAAAGAGCTGTTCAGAGTAGGTGGCGACGTCCCTGAGACCAACTACCTCTTCATG
GGGGACTTTGTGGACCGTGGCTTCTATAGCGTCGAAACGTTCCTCCTGCTGCTGGCACTT
AAGGTTCGCTATCCTGATCGCATCACACTGATCCGGGGCAACCATGAGAGTCGCCAGATC
ACGCAGGTCTATGGCTTCTACGATGAGTGCCTGCGCAAGTACGGCTCGGTGACTGTGTGG
CGCTACTGCACTGAGATCTTTGACTACCTCAGCCTGTCAGCCATCATCGATGGCAAGATC
TTCTGCGTGCACGGGGGCCTCTCCCCCTCCATCCAGACCCTGGATCAGATTCGGACAATC
GACCGAAAGCAAGAGGTGCCTCATGATGGGCCCATGTGTGACCTCCTCTGGTCTGACCCA
GAAGACACCACAGGCTGGGGCGTGAGCCCCCGAGGAGCCGGCTACCTATTTGGCAGTGAC
GTGGTGGCCCAGTTCAACGCAGCCAATGACATTGACATGATCTGCCGTGCCCACCAACTG
GTGATGGAAGGTTACAAGTGGCACTTCAATGAGACGGTGCTCACTGTGTGGTCGGCACCC
AACTACTGCTACCGCTGTGGGAATGTGGCAGCCATCTTGGAGCTGGACGAGCATCTCCAG
AAAGATTTCATCATCTTTGAGGCTGCTCCCCAAGAGACACGGGGCATCCCCTCCAAGAAG
CCCGTGGCCGACTACTTCCTGTGA
Protein Properties
Number of Residues 307
Molecular Weight 35079.6
Theoretical pI 5.061
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Serine/threonine-protein phosphatase 4 catalytic subunit
MAEISDLDRQIEQLRRCELIKESEVKALCAKAREILVEESNVQRVDSPVTVCGDIHGQFY
DLKELFRVGGDVPETNYLFMGDFVDRGFYSVETFLLLLALKVRYPDRITLIRGNHESRQI
TQVYGFYDECLRKYGSVTVWRYCTEIFDYLSLSAIIDGKIFCVHGGLSPSIQTLDQIRTI
DRKQEVPHDGPMCDLLWSDPEDTTGWGVSPRGAGYLFGSDVVAQFNAANDIDMICRAHQL
VMEGYKWHFNETVLTVWSAPNYCYRCGNVAAILELDEHLQKDFIIFEAAPQETRGIPSKK
PVADYFL
GenBank ID Protein 4028575
UniProtKB/Swiss-Prot ID P60510
UniProtKB/Swiss-Prot Entry Name PP4C_HUMAN
PDB IDs Not Available
GenBank Gene ID AF097996
GeneCard ID PPP4C
GenAtlas ID PPP4C
HGNC ID HGNC:9319
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  3. Brewis ND, Cohen PT: Protein phosphatase X has been highly conserved during mammalian evolution. Biochim Biophys Acta. 1992 Dec 29;1171(2):231-3. [PubMed:1336397 ]
  4. Hu MC, Tang-Oxley Q, Qiu WR, Wang YP, Mihindukulasuriya KA, Afshar R, Tan TH: Protein phosphatase X interacts with c-Rel and stimulates c-Rel/nuclear factor kappaB activity. J Biol Chem. 1998 Dec 11;273(50):33561-5. [PubMed:9837938 ]
  5. Zhou G, Mihindukulasuriya KA, MacCorkle-Chosnek RA, Van Hooser A, Hu MC, Brinkley BR, Tan TH: Protein phosphatase 4 is involved in tumor necrosis factor-alpha-induced activation of c-Jun N-terminal kinase. J Biol Chem. 2002 Feb 22;277(8):6391-8. Epub 2001 Nov 6. [PubMed:11698396 ]
  6. Mourtada-Maarabouni M, Kirkham L, Jenkins B, Rayner J, Gonda TJ, Starr R, Trayner I, Farzaneh F, Williams GT: Functional expression cloning reveals proapoptotic role for protein phosphatase 4. Cell Death Differ. 2003 Sep;10(9):1016-24. [PubMed:12934076 ]
  7. Carnegie GK, Sleeman JE, Morrice N, Hastie CJ, Peggie MW, Philp A, Lamond AI, Cohen PT: Protein phosphatase 4 interacts with the Survival of Motor Neurons complex and enhances the temporal localisation of snRNPs. J Cell Sci. 2003 May 15;116(Pt 10):1905-13. Epub 2003 Mar 18. [PubMed:12668731 ]
  8. Mihindukulasuriya KA, Zhou G, Qin J, Tan TH: Protein phosphatase 4 interacts with and down-regulates insulin receptor substrate 4 following tumor necrosis factor-alpha stimulation. J Biol Chem. 2004 Nov 5;279(45):46588-94. Epub 2004 Aug 24. [PubMed:15331607 ]
  9. Zhang X, Ozawa Y, Lee H, Wen YD, Tan TH, Wadzinski BE, Seto E: Histone deacetylase 3 (HDAC3) activity is regulated by interaction with protein serine/threonine phosphatase 4. Genes Dev. 2005 Apr 1;19(7):827-39. [PubMed:15805470 ]
  10. Gingras AC, Caballero M, Zarske M, Sanchez A, Hazbun TR, Fields S, Sonenberg N, Hafen E, Raught B, Aebersold R: A novel, evolutionarily conserved protein phosphatase complex involved in cisplatin sensitivity. Mol Cell Proteomics. 2005 Nov;4(11):1725-40. Epub 2005 Aug 5. [PubMed:16085932 ]
  11. Nakada S, Chen GI, Gingras AC, Durocher D: PP4 is a gamma H2AX phosphatase required for recovery from the DNA damage checkpoint. EMBO Rep. 2008 Oct;9(10):1019-26. doi: 10.1038/embor.2008.162. Epub 2008 Aug 29. [PubMed:18758438 ]
  12. Martin-Granados C, Philp A, Oxenham SK, Prescott AR, Cohen PT: Depletion of protein phosphatase 4 in human cells reveals essential roles in centrosome maturation, cell migration and the regulation of Rho GTPases. Int J Biochem Cell Biol. 2008;40(10):2315-32. doi: 10.1016/j.biocel.2008.03.021. Epub 2008 Apr 8. [PubMed:18487071 ]
  13. Chen GI, Tisayakorn S, Jorgensen C, D'Ambrosio LM, Goudreault M, Gingras AC: PP4R4/KIAA1622 forms a novel stable cytosolic complex with phosphoprotein phosphatase 4. J Biol Chem. 2008 Oct 24;283(43):29273-84. doi: 10.1074/jbc.M803443200. Epub 2008 Aug 20. [PubMed:18715871 ]
  14. 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: Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1 dephosphorylation. J Cell Biol. 2008 Mar 24;180(6):1133-47. doi: 10.1083/jcb.200705148. Epub 2008 Mar 17. [PubMed:18347064 ]
  15. Chowdhury D, Xu X, Zhong X, Ahmed F, Zhong J, Liao J, Dykxhoorn DM, Weinstock DM, Pfeifer GP, Lieberman J: A PP4-phosphatase complex dephosphorylates gamma-H2AX generated during DNA replication. Mol Cell. 2008 Jul 11;31(1):33-46. doi: 10.1016/j.molcel.2008.05.016. [PubMed:18614045 ]