Serine/threonine-protein phosphatase 5

NameSerine/threonine-protein phosphatase 5
Synonyms
  • 3.1.3.16
  • PP-T
  • PP5
  • PPP5
  • PPT
  • Protein phosphatase T
Gene NamePPP5C
OrganismHuman
Amino acid sequence
>lcl|BSEQ0012211|Serine/threonine-protein phosphatase 5
MAMAEGERTECAEPPRDEPPADGALKRAEELKTQANDYFKAKDYENAIKFYSQAIELNPS
NAIYYGNRSLAYLRTECYGYALGDATRAIELDKKYIKGYYRRAASNMALGKFRAALRDYE
TVVKVKPHDKDAKMKYQECNKIVKQKAFERAIAGDEHKRSVVDSLDIESMTIEDEYSGPK
LEDGKVTISFMKELMQWYKDQKKLHRKCAYQILVQVKEVLSKLSTLVETTLKETEKITVC
GDTHGQFYDLLNIFELNGLPSETNPYIFNGDFVDRGSFSVEVILTLFGFKLLYPDHFHLL
RGNHETDNMNQIYGFEGEVKAKYTAQMYELFSEVFEWLPLAQCINGKVLIMHGGLFSEDG
VTLDDIRKIERNRQPPDSGPMCDLLWSDPQPQNGRSISKRGVSCQFGPDVTKAFLEENNL
DYIIRSHEVKAEGYEVAHGGRCVTVFSAPNYCDQMGNKASYIHLQGSDLRPQFHQFTAVP
HPNVKPMAYANTLLQLGMM
Number of residues499
Molecular Weight56878.22
Theoretical pI6.21
GO Classification
Functions
  • ADP binding
  • signal transducer activity
  • identical protein binding
  • ATP binding
  • RNA binding
  • lipid binding
  • phosphoprotein phosphatase activity
  • protein serine/threonine phosphatase activity
  • metal ion binding
Processes
  • cellular response to hydrogen peroxide
  • innate immune response
  • mitotic nuclear division
  • response to morphine
  • Fc-epsilon receptor signaling pathway
  • response to lead ion
  • positive regulation of I-kappaB kinase/NF-kappaB signaling
  • activation of MAPKK activity
  • fibroblast growth factor receptor signaling pathway
  • DNA repair
  • negative regulation of protein phosphorylation
  • insulin receptor signaling pathway
  • negative regulation of neuron death
  • MAPK cascade
  • neurotrophin TRK receptor signaling pathway
  • small GTPase mediated signal transduction
  • cellular response to cadmium ion
  • Ras protein signal transduction
  • vascular endothelial growth factor receptor signaling pathway
  • histone dephosphorylation
  • positive regulation of glucocorticoid receptor signaling pathway
  • transcription, DNA-templated
  • axon guidance
  • protein heterooligomerization
  • double-strand break repair
  • protein dephosphorylation
  • epidermal growth factor receptor signaling pathway
Components
  • membrane
  • protein complex
  • intracellular membrane-bounded organelle
  • nucleus
  • cell periphery
  • proximal dendrite
  • cytosol
  • perikaryon
  • nucleoplasm
  • cytoplasm
General FunctionSignal transducer activity
Specific FunctionSerine/threonine-protein phosphatase that dephosphorylates a myriad of proteins involved in different signaling pathways including the kinases CSNK1E, ASK1/MAP3K5, PRKDC and RAF1, the nuclear receptors NR3C1, PPARG, ESR1 and ESR2, SMAD proteins and TAU/MAPT. Implicated in wide ranging cellular processes, including apoptosis, differentiation, DNA damage response, cell survival, regulation of ion channels or circadian rhythms, in response to steroid and thyroid hormones, calcium, fatty acids, TGF-beta as well as oxidative and genotoxic stresses. Participates in the control of DNA damage response mechanisms such as checkpoint activation and DNA damage repair through, for instance, the regulation ATM/ATR-signaling and dephosphorylation of PRKDC and TP53BP1. Inhibits ASK1/MAP3K5-mediated apoptosis induced by oxidative stress. Plays a positive role in adipogenesis, mainly through the dephosphorylation and activation of PPARG transactivation function. Also dephosphorylates and inhibits the anti-adipogenic effect of NR3C1. Regulates the circadian rhythms, through the dephosphorylation and activation of CSNK1E. May modulate TGF-beta signaling pathway by the regulation of SMAD3 phosphorylation and protein expression levels. Dephosphorylates and may play a role in the regulation of TAU/MAPT. Through their dephosphorylation, may play a role in the regulation of ions channels such as KCNH2.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP53041
UniProtKB Entry NamePPP5_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0006165|1483 bp
CGAGAGGACTGAGTGTGCTGAGCCCCCCCGGGACGAACCCCCGGCTGATGGAGCTCTGAA
GCGGGCAGAGGAGCTCAAGACTCAGGCCAATGACTACTTCAAAGCCAAGGACTACGAGAA
CGCCATCAAGTTCTACAGCCAGGCCATCGAGCTGAACCCCAGCAATGCCATCTACTATGG
CAACCGCAGCCTGGCCTACCTGCGCACTGAGTGCTATGGCTACGCGCTGGGAGACGCCAC
GCGGGCCATTGAGCTGGACAAGAAGTACATCAAGGGTTATTACCGCCGGGCTGCCAGCAA
CATGGCACTGGGCAAGTTCCGGGCCGCGCTGCGAGACTACGAGACGGTGGTCAAGGTGAA
GCCCCATGACAAGGATGCCAAAATGAAATACCAGGAGTGCAACAAGATCGTGAAGCAGAA
GGCCTTTGAGCGGGCCATCGCGGGCGACGAGCACAAGCGCTCCGTGGTGGACTCGCTGGA
CATCGAGAGCATGACCATTGAGGATGAGTACAGCGGACCCAAGCTTGAAGACGGCAAAGT
GACAATCAGTTTCATGAAGGAGCTCATGCAGTGGTACAAGGACCAGAAGAAACTGCACCG
GAAATGTGCCTACCAGATTCTGGTACAGGTCAAAGAGGTCCTCTCCAAGCTGAGCACGCT
CGTGGAAACCACACTCAAAGAGACAGAGAAGATTACAGTATGTGGGGACACCCATGGCCA
GTTCTATGACCTCCTCAACATATTCGAGCTCAACGGTTTACCCTCGGAGACCAACCCCTA
TATATTTAATGGTGACTTTGTGGACCGAGGCTCCTTCTCTGTAGAAGTGATCCTCACCCT
TTTCGGCTTCAAGCTCCTGTACCCAGATCACTTTCACCTCCTTCGAGGCAACCACGAGAC
AGACAACATGAACCAGATCTACGGTTTCGAGGGTGAGGTGAAGGCCAAGTACACAGCCCA
GATGTACGAGCTCTTTAGCGAGGTGTTCGAGTGGCTCCCGTTGGCCCAGTGCATCAACGG
CAAAGTGCTGATCATGCACGGAGGCCTGTTCAGTGAAGACGGTGTCACCCTGGATGACAT
CCGGAAAATTGAGCGGAATCGACAACCCCCAGATTCAGGGCCCATGTGTGACCTGCTCTG
GTCAGATCCACAGCCACAGAACGGGCGCTCGATCAGCAAGCGGGGCGTGAGCTGTCAGTT
TGGGCCTGACGTCACCAAGGCCTTCTTGGAAGAGAACAACCTGGACTATATCATCCGCAG
CCACGAAGTCAAGGCCGAGGGCTACGAGGTGGCTCACGGAGGCCGCTGTGTCACCGTCTT
CTCTGCCCCCAACTACTGCGACCAGATGGGGAACAAAGCCTCCTACATCCACCTCCAGGG
CTCTGACCTACGGCCTCAGTTCCACCAGTTCACAGCAGTGCCTCATCCCAACGTCAAGCC
CATGGCCTATGCCAACACGCTGCTGCAGCTAGGAATGATGTGA
GenBank Gene IDX89416
GeneCard IDNot Available
GenAtlas IDPPP5C
HGNC IDHGNC:9322
Chromosome LocationNot Available
Locus19q13.3
References
  1. Chen MX, McPartlin AE, Brown L, Chen YH, Barker HM, Cohen PT: A novel human protein serine/threonine phosphatase, which possesses four tetratricopeptide repeat motifs and localizes to the nucleus. EMBO J. 1994 Sep 15;13(18):4278-90. 7925273
  2. Yong WH, Ueki K, Chou D, Reeves SA, von Deimling A, Gusella JF, Mohrenweiser HW, Buckler AJ, Louis DN: Cloning of a highly conserved human protein serine-threonine phosphatase gene from the glioma candidate region on chromosome 19q13.3. Genomics. 1995 Sep 20;29(2):533-6. 8666404
  3. Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM: The DNA sequence and biology of human chromosome 19. Nature. 2004 Apr 1;428(6982):529-35. 15057824
  4. 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. 15489334
  5. Xu X, Lagercrantz J, Zickert P, Bajalica-Lagercrantz S, Zetterberg A: Chromosomal localization and 5' sequence of the human protein serine/threonine phosphatase 5' gene. Biochem Biophys Res Commun. 1996 Jan 17;218(2):514-7. 8561788
  6. Chen MX, Cohen PT: Activation of protein phosphatase 5 by limited proteolysis or the binding of polyunsaturated fatty acids to the TPR domain. FEBS Lett. 1997 Jan 2;400(1):136-40. 9000529
  7. Ollendorff V, Donoghue DJ: The serine/threonine phosphatase PP5 interacts with CDC16 and CDC27, two tetratricopeptide repeat-containing subunits of the anaphase-promoting complex. J Biol Chem. 1997 Dec 19;272(51):32011-8. 9405394
  8. Ali A, Zhang J, Bao S, Liu I, Otterness D, Dean NM, Abraham RT, Wang XF: Requirement of protein phosphatase 5 in DNA-damage-induced ATM activation. Genes Dev. 2004 Feb 1;18(3):249-54. 14871926
  9. Ikeda K, Ogawa S, Tsukui T, Horie-Inoue K, Ouchi Y, Kato S, Muramatsu M, Inoue S: Protein phosphatase 5 is a negative regulator of estrogen receptor-mediated transcription. Mol Endocrinol. 2004 May;18(5):1131-43. Epub 2004 Feb 5. 14764652
  10. Wechsler T, Chen BP, Harper R, Morotomi-Yano K, Huang BC, Meek K, Cleaver JE, Chen DJ, Wabl M: DNA-PKcs function regulated specifically by protein phosphatase 5. Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1247-52. Epub 2004 Jan 20. 14734805
  11. Zeke T, Morrice N, Vazquez-Martin C, Cohen PT: Human protein phosphatase 5 dissociates from heat-shock proteins and is proteolytically activated in response to arachidonic acid and the microtubule-depolymerizing drug nocodazole. Biochem J. 2005 Jan 1;385(Pt 1):45-56. 15383005
  12. Liu F, Iqbal K, Grundke-Iqbal I, Rossie S, Gong CX: Dephosphorylation of tau by protein phosphatase 5: impairment in Alzheimer's disease. J Biol Chem. 2005 Jan 21;280(3):1790-6. Epub 2004 Nov 15. 15546861
  13. Zhang J, Bao S, Furumai R, Kucera KS, Ali A, Dean NM, Wang XF: Protein phosphatase 5 is required for ATR-mediated checkpoint activation. Mol Cell Biol. 2005 Nov;25(22):9910-9. 16260606
  14. von Kriegsheim A, Pitt A, Grindlay GJ, Kolch W, Dhillon AS: Regulation of the Raf-MEK-ERK pathway by protein phosphatase 5. Nat Cell Biol. 2006 Sep;8(9):1011-6. Epub 2006 Aug 6. 16892053
  15. Partch CL, Shields KF, Thompson CL, Selby CP, Sancar A: Posttranslational regulation of the mammalian circadian clock by cryptochrome and protein phosphatase 5. Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10467-72. Epub 2006 Jun 21. 16790549
  16. 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. 19413330
  17. Kang Y, Lee JH, Hoan NN, Sohn HM, Chang IY, You HJ: Protein phosphatase 5 regulates the function of 53BP1 after neocarzinostatin-induced DNA damage. J Biol Chem. 2009 Apr 10;284(15):9845-53. doi: 10.1074/jbc.M809272200. Epub 2009 Jan 28. 19176521
  18. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. 19608861
  19. Chatterjee A, Wang L, Armstrong DL, Rossie S: Activated Rac1 GTPase translocates protein phosphatase 5 to the cell membrane and stimulates phosphatase activity in vitro. J Biol Chem. 2010 Feb 5;285(6):3872-82. doi: 10.1074/jbc.M109.088427. Epub 2009 Nov 30. 19948726
  20. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  21. Kang Y, Cheong HM, Lee JH, Song PI, Lee KH, Kim SY, Jun JY, You HJ: Protein phosphatase 5 is necessary for ATR-mediated DNA repair. Biochem Biophys Res Commun. 2011 Jan 7;404(1):476-81. doi: 10.1016/j.bbrc.2010.12.005. Epub 2010 Dec 6. 21144835
  22. Bruce DL, Macartney T, Yong W, Shou W, Sapkota GP: Protein phosphatase 5 modulates SMAD3 function in the transforming growth factor-beta pathway. Cell Signal. 2012 Nov;24(11):1999-2006. doi: 10.1016/j.cellsig.2012.07.003. Epub 2012 Jul 7. 22781750
  23. Yamaguchi F, Umeda Y, Shimamoto S, Tsuchiya M, Tokumitsu H, Tokuda M, Kobayashi R: S100 proteins modulate protein phosphatase 5 function: a link between CA2+ signal transduction and protein dephosphorylation. J Biol Chem. 2012 Apr 20;287(17):13787-98. doi: 10.1074/jbc.M111.329771. Epub 2012 Mar 7. 22399290
  24. Sekine Y, Hatanaka R, Watanabe T, Sono N, Iemura S, Natsume T, Kuranaga E, Miura M, Takeda K, Ichijo H: The Kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1 activation by suppressing PP5. Mol Cell. 2012 Dec 14;48(5):692-704. doi: 10.1016/j.molcel.2012.09.018. Epub 2012 Oct 25. 23102700
  25. Das AK, Cohen PW, Barford D: The structure of the tetratricopeptide repeats of protein phosphatase 5: implications for TPR-mediated protein-protein interactions. EMBO J. 1998 Mar 2;17(5):1192-9. 9482716
  26. Swingle MR, Honkanen RE, Ciszak EM: Structural basis for the catalytic activity of human serine/threonine protein phosphatase-5. J Biol Chem. 2004 Aug 6;279(32):33992-9. Epub 2004 May 23. 15155720
  27. Yang J, Roe SM, Cliff MJ, Williams MA, Ladbury JE, Cohen PT, Barford D: Molecular basis for TPR domain-mediated regulation of protein phosphatase 5. EMBO J. 2005 Jan 12;24(1):1-10. Epub 2004 Dec 2. 15577939
  28. Cliff MJ, Harris R, Barford D, Ladbury JE, Williams MA: Conformational diversity in the TPR domain-mediated interaction of protein phosphatase 5 with Hsp90. Structure. 2006 Mar;14(3):415-26. 16531226
  29. Bertini I, Calderone V, Fragai M, Luchinat C, Talluri E: Structural basis of serine/threonine phosphatase inhibition by the archetypal small molecules cantharidin and norcantharidin. J Med Chem. 2009 Aug 13;52(15):4838-43. doi: 10.1021/jm900610k. 19601647