Serine/threonine-protein phosphatase PP1-gamma catalytic subunit

NameSerine/threonine-protein phosphatase PP1-gamma catalytic subunit
Synonyms
  • 3.1.3.16
  • PP-1G
  • Protein phosphatase 1C catalytic subunit
Gene NamePPP1CC
OrganismHuman
Amino acid sequence
>lcl|BSEQ0002872|Serine/threonine-protein phosphatase PP1-gamma catalytic subunit
MADLDKLNIDSIIQRLLEVRGSKPGKNVQLQENEIRGLCLKSREIFLSQPILLELEAPLK
ICGDIHGQYYDLLRLFEYGGFPPESNYLFLGDYVDRGKQSLETICLLLAYKIKYPENFFL
LRGNHECASINRIYGFYDECKRRYNIKLWKTFTDCFNCLPIAAIVDEKIFCCHGGLSPDL
QSMEQIRRIMRPTDVPDQGLLCDLLWSDPDKDVLGWGENDRGVSFTFGAEVVAKFLHKHD
LDLICRAHQVVEDGYEFFAKRQLVTLFSAPNYCGEFDNAGAMMSVDETLMCSFQILKPAE
KKKPNATRPVTPPRGMITKQAKK
Number of residues323
Molecular Weight36983.4
Theoretical pI6.5
GO Classification
Functions
  • phosphoprotein phosphatase activity
  • phosphatase activity
  • metal ion binding
  • protein N-terminus binding
  • protein serine/threonine phosphatase activity
  • protein kinase binding
  • poly(A) RNA binding
Processes
  • regulation of circadian rhythm
  • circadian regulation of gene expression
  • small GTPase mediated signal transduction
  • triglyceride catabolic process
  • cell division
  • small molecule metabolic process
  • glycogen metabolic process
  • neuron differentiation
  • mitotic cell cycle
  • negative regulation of transforming growth factor beta receptor signaling pathway
  • entrainment of circadian clock by photoperiod
  • transforming growth factor beta receptor signaling pathway
  • protein dephosphorylation
Components
  • dendritic spine
  • protein complex
  • nucleus
  • midbody
  • cleavage furrow
  • cytosol
  • nuclear speck
  • nucleolus
  • condensed chromosome kinetochore
  • focal adhesion
  • cytoplasm
  • PTW/PP1 phosphatase complex
  • mitochondrion
  • MLL5-L complex
General FunctionProtein serine/threonine phosphatase activity
Specific FunctionProtein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Dephosphorylates RPS6KB1. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID402778
UniProtKB IDP36873
UniProtKB Entry NamePP1G_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0021660|Serine/threonine-protein phosphatase PP1-gamma catalytic subunit (PPP1CC)
ATGGCGGATTTAGATAAACTCAACATCGACAGCATTATCCAACGGCTGCTGGAAGTGAGA
GGGTCCAAGCCTGGTAAGAATGTCCAGCTTCAGGAGAATGAAATCAGAGGACTGTGCTTA
AAGTCTCGTGAAATCTTTCTCAGTCAGCCTATCCTACTAGAACTTGAAGCACCACTCAAA
ATATGTGGTGACATCCATGGACAATACTATGATTTGCTGCGACTTTTTGAGTACGGTGGT
TTCCCACCAGAAAGCAACTACCTGTTTCTTGGGGACTATGTGGACAGGGGAAAGCAGTCA
TTGGAGACGATCTGCCTCTTACTGGCCTACAAAATAAAATATCCTGAGAATTTTTTTCTT
CTCAGAGGGAACCATGAATGTGCCAGCATCAACAGAATTTATGGATTTTATGATGAATGT
AAAAGAAGATACAACATTAAACTATGGAAAACTTTCACAGACTGTTTTAACTGTTTACCG
ATAGCAGCCATCGTGGATGAGAAGATATTCTGCTGTCATGGAGGTTTATCACCAGATCTT
CAATCTATGGAGCAGATTCGGCGAATTATGCGACCAACTGATGTACCAGATCAAGGTCTT
CTTTGTGATCTTTTGTGGTCTGACCCCGATAAAGATGTCTTAGGCTGGGGTGAAAATGAC
AGAGGAGTGTCCTTCACATTTGGTGCAGAAGTGGTTGCAAAATTTCTCCATAAGCATGAT
TTGGATCTTATATGTAGAGCCCATCAGGTGGTTGAAGATGGATATGAATTTTTTGCAAAG
AGGCAGTTGGTCACTCTGTTTTCTGCGCCCAATTATTGCGGAGAGTTTGACAATGCAGGT
GCCATGATGAGTGTGGATGAAACACTAATGTGTTCTTTTCAGATTTTAAAGCCTGCAGAG
AAAAAGAAGCCAAATGCCACGAGACCTGTAACGCCTCCAAGGGTTGCATCAGGCCTGAAC
CCGTCCATTCAGAAAGCTTCAAATTATAGAAACAATACTGTTCTATACGAGTGA
GenBank Gene IDX74008
GeneCard IDNot Available
GenAtlas IDPPP1CC
HGNC IDHGNC:9283
Chromosome Location12
Locus12q24.1-q24.2
References
  1. Barker HM, Craig SP, Spurr NK, Cohen PT: Sequence of human protein serine/threonine phosphatase 1 gamma and localization of the gene (PPP1CC) encoding it to chromosome bands 12q24.1-q24.2. Biochim Biophys Acta. 1993 Aug 18;1178(2):228-33. 8394140
  2. 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
  3. Norman SA, Mott DM: Molecular cloning and chromosomal localization of a human skeletal muscle PP-1 gamma 1 cDNA. Mamm Genome. 1994 Jan;5(1):41-5. 8111128
  4. MacKintosh RW, Dalby KN, Campbell DG, Cohen PT, Cohen P, MacKintosh C: The cyanobacterial toxin microcystin binds covalently to cysteine-273 on protein phosphatase 1. FEBS Lett. 1995 Sep 11;371(3):236-40. 7556599
  5. Armstrong CG, Browne GJ, Cohen P, Cohen PT: PPP1R6, a novel member of the family of glycogen-targetting subunits of protein phosphatase 1. FEBS Lett. 1997 Nov 24;418(1-2):210-4. 9414128
  6. Trinkle-Mulcahy L, Sleeman JE, Lamond AI: Dynamic targeting of protein phosphatase 1 within the nuclei of living mammalian cells. J Cell Sci. 2001 Dec;114(Pt 23):4219-28. 11739654
  7. Connor JH, Weiser DC, Li S, Hallenbeck JM, Shenolikar S: Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1. Mol Cell Biol. 2001 Oct;21(20):6841-50. 11564868
  8. Ceulemans H, Vulsteke V, De Maeyer M, Tatchell K, Stalmans W, Bollen M: Binding of the concave surface of the Sds22 superhelix to the alpha 4/alpha 5/alpha 6-triangle of protein phosphatase-1. J Biol Chem. 2002 Dec 6;277(49):47331-7. Epub 2002 Sep 10. 12226088
  9. Trinkle-Mulcahy L, Andrews PD, Wickramasinghe S, Sleeman J, Prescott A, Lam YW, Lyon C, Swedlow JR, Lamond AI: Time-lapse imaging reveals dynamic relocalization of PP1gamma throughout the mammalian cell cycle. Mol Biol Cell. 2003 Jan;14(1):107-17. 12529430
  10. Fardilha M, Wu W, Sa R, Fidalgo S, Sousa C, Mota C, da Cruz e Silva OA, da Cruz e Silva EF: Alternatively spliced protein variants as potential therapeutic targets for male infertility and contraception. Ann N Y Acad Sci. 2004 Dec;1030:468-78. 15659832
  11. Boyce M, Bryant KF, Jousse C, Long K, Harding HP, Scheuner D, Kaufman RJ, Ma D, Coen DM, Ron D, Yuan J: A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress. Science. 2005 Feb 11;307(5711):935-9. 15705855
  12. Trinkle-Mulcahy L, Andersen J, Lam YW, Moorhead G, Mann M, Lamond AI: Repo-Man recruits PP1 gamma to chromatin and is essential for cell viability. J Cell Biol. 2006 Feb 27;172(5):679-92. Epub 2006 Feb 21. 16492807
  13. Mi J, Guo C, Brautigan DL, Larner JM: Protein phosphatase-1alpha regulates centrosome splitting through Nek2. Cancer Res. 2007 Feb 1;67(3):1082-9. 17283141
  14. Djouder N, Metzler SC, Schmidt A, Wirbelauer C, Gstaiger M, Aebersold R, Hess D, Krek W: S6K1-mediated disassembly of mitochondrial URI/PP1gamma complexes activates a negative feedback program that counters S6K1 survival signaling. Mol Cell. 2007 Oct 12;28(1):28-40. 17936702
  15. Gunawardena SR, Ruis BL, Meyer JA, Kapoor M, Conklin KF: NOM1 targets protein phosphatase I to the nucleolus. J Biol Chem. 2008 Jan 4;283(1):398-404. Epub 2007 Oct 26. 17965019
  16. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  17. Fujiki R, Chikanishi T, Hashiba W, Ito H, Takada I, Roeder RG, Kitagawa H, Kato S: GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis. Nature. 2009 May 21;459(7245):455-9. doi: 10.1038/nature07954. Epub 2009 Apr 19. 19377461
  18. Lee JH, You J, Dobrota E, Skalnik DG: Identification and characterization of a novel human PP1 phosphatase complex. J Biol Chem. 2010 Aug 6;285(32):24466-76. doi: 10.1074/jbc.M110.109801. Epub 2010 Jun 1. 20516061
  19. 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
  20. Schmutz I, Wendt S, Schnell A, Kramer A, Mansuy IM, Albrecht U: Protein phosphatase 1 (PP1) is a post-translational regulator of the mammalian circadian clock. PLoS One. 2011;6(6):e21325. doi: 10.1371/journal.pone.0021325. Epub 2011 Jun 21. 21712997
  21. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. 22814378
  22. Nie H, Zheng Y, Li R, Guo TB, He D, Fang L, Liu X, Xiao L, Chen X, Wan B, Chin YE, Zhang JZ: Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNF-alpha in rheumatoid arthritis. Nat Med. 2013 Mar;19(3):322-8. doi: 10.1038/nm.3085. Epub 2013 Feb 10. 23396208
  23. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  24. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. 25944712
  25. Egloff MP, Cohen PT, Reinemer P, Barford D: Crystal structure of the catalytic subunit of human protein phosphatase 1 and its complex with tungstate. J Mol Biol. 1995 Dec 15;254(5):942-59. 7500362
  26. Maynes JT, Bateman KS, Cherney MM, Das AK, Luu HA, Holmes CF, James MN: Crystal structure of the tumor-promoter okadaic acid bound to protein phosphatase-1. J Biol Chem. 2001 Nov 23;276(47):44078-82. Epub 2001 Sep 4. 11535607
  27. Maynes JT, Perreault KR, Cherney MM, Luu HA, James MN, Holmes CF: Crystal structure and mutagenesis of a protein phosphatase-1:calcineurin hybrid elucidate the role of the beta12-beta13 loop in inhibitor binding. J Biol Chem. 2004 Oct 8;279(41):43198-206. Epub 2004 Jul 26. 15280359