NameProtein phosphatase 1A
Synonyms
  • 3.1.3.16
  • PP2C-alpha
  • PPPM1A
  • Protein phosphatase 2C isoform alpha
  • Protein phosphatase IA
Gene NamePPM1A
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009180|Protein phosphatase 1A
MGAFLDKPKMEKHNAQGQGNGLRYGLSSMQGWRVEMEDAHTAVIGLPSGLESWSFFAVYD
GHAGSQVAKYCCEHLLDHITNNQDFKGSAGAPSVENVKNGIRTGFLEIDEHMRVMSEKKH
GADRSGSTAVGVLISPQHTYFINCGDSRGLLCRNRKVHFFTQDHKPSNPLEKERIQNAGG
SVMIQRVNGSLAVSRALGDFDYKCVHGKGPTEQLVSPEPEVHDIERSEEDDQFIILACDG
IWDVMGNEELCDFVRSRLEVTDDLEKVCNEVVDTCLYKGSRDNMSVILICFPNAPKVSPE
AVKKEAELDKYLECRVEEIIKKQGEGVPDLVHVMRTLASENIPSLPPGGELASKRNVIEA
VYNRLNPYKNDDTDSTSTDDMW
Number of residues382
Molecular Weight42447.455
Theoretical pINot Available
GO Classification
Functions
  • signal transducer activity
  • manganese ion binding
  • magnesium ion binding
  • R-SMAD binding
  • protein serine/threonine phosphatase activity
  • calmodulin-dependent protein phosphatase activity
Processes
  • transforming growth factor beta receptor signaling pathway
  • protein dephosphorylation
  • dephosphorylation
  • Wnt signaling pathway
  • cell cycle arrest
  • positive regulation of I-kappaB kinase/NF-kappaB signaling
  • positive regulation of Wnt signaling pathway
  • negative regulation of I-kappaB kinase/NF-kappaB signaling
  • N-terminal protein myristoylation
  • gene expression
  • positive regulation of protein export from nucleus
  • transcription initiation from RNA polymerase II promoter
  • negative regulation of transforming growth factor beta receptor signaling pathway
  • negative regulation of NF-kappaB import into nucleus
  • positive regulation of transcription, DNA-templated
  • negative regulation of BMP signaling pathway
  • insulin receptor signaling pathway
  • peptidyl-threonine dephosphorylation
  • negative regulation of transcription from RNA polymerase II promoter
  • negative regulation of SMAD protein complex assembly
  • transcription, DNA-templated
Components
  • voltage-gated calcium channel complex
  • nucleus
  • cytosol
  • nucleoplasm
  • neuron projection
  • membrane
General FunctionSignal transducer activity
Specific FunctionEnzyme with a broad specificity. Negatively regulates TGF-beta signaling through dephosphorylating SMAD2 and SMAD3, resulting in their dissociation from SMAD4, nuclear export of the SMADs and termination of the TGF-beta-mediated signaling. Dephosphorylates PRKAA1 and PRKAA2. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP35813
UniProtKB Entry NamePPM1A_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0017713|Protein phosphatase 1A (PPM1A)
ATGGGAGCATTTTTAGACAAGCCAAAGATGGAAAAGCATAATGCCCAGGGGCAGGGTAAT
GGGTTGCGATATGGGCTAAGCAGCATGCAAGGCTGGCGTGTTGAAATGGAGGATGCACAT
ACGGCTGTGATCGGTTTGCCAAGTGGACTTGAATCGTGGTCATTCTTTGCTGTGTATGAT
GGGCATGCTGGTTCTCAGGTTGCCAAATACTGCTGTGAGCATTTGTTAGATCACATCACC
AATAACCAGGATTTTAAAGGGTCTGCAGGAGCACCTTCTGTGGAAAATGTAAAGAATGGA
ATCAGAACAGGTTTTCTGGAGATTGATGAACACATGAGAGTTATGTCAGAGAAGAAACAT
GGTGCAGATAGAAGTGGGTCAACAGCTGTAGGTGTCTTAATTTCTCCCCAACATACTTAT
TTCATTAACTGTGGAGACTCAAGAGGTTTACTTTGTAGGAACAGGAAAGTTCATTTCTTC
ACACAAGATCACAAACCAAGTAATCCGCTGGAGAAAGAACGAATTCAGAATGCAGGTGGC
TCTGTAATGATTCAGCGTGTGAATGGCTCTCTGGCTGTATCGAGGGCCCTTGGGGATTTT
GATTACAAATGTGTCCATGGAAAAGGTCCTACTGAGCAGCTTGTCTCACCAGAGCCTGAA
GTCCATGATATTGAAAGATCTGAAGAAGATGATCAGTTCATTATCCTTGCATGTGATGGT
ATCTGGGATGTTATGGGAAATGAAGAGCTCTGTGATTTTGTAAGATCCAGACTTGAAGTC
ACTGATGACCTTGAGAAAGTTTGCAATGAAGTAGTCGACACCTGTTTGTATAAGGGAAGT
CGAGACAACATGAGTGTGATTTTGATCTGTTTTCCAAATGCACCCAAAGTATCGCCAGAA
GCAGTGAAGAAGGAGGCAGAGTTGGACAAGTACCTGGAATGCAGAGTAGAAGAAATCATA
AAGAAGCAGGGGGAAGGCGTCCCCGACTTAGTCCATGTGATGCGCACATTAGCGAGTGAG
AACATCCCCAGCCTCCCACCAGGGGGTGAATTGGCAAGCAAGAGGAATGTTATTGAAGCC
GTTTACAATAGACTGAATCCTTACAAAAATGACGACACTGACTCTACATCAACAGATGAT
ATGTGGTAA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:9275
Chromosome Location14
LocusNot Available
References
  1. Mann DJ, Campbell DG, McGowan CH, Cohen PT: Mammalian protein serine/threonine phosphatase 2C: cDNA cloning and comparative analysis of amino acid sequences. Biochim Biophys Acta. 1992 Feb 28;1130(1):100-4. 1311954
  2. Takekawa M, Maeda T, Saito H: Protein phosphatase 2Calpha inhibits the human stress-responsive p38 and JNK MAPK pathways. EMBO J. 1998 Aug 17;17(16):4744-52. 9707433
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  4. Goshima N, Kawamura Y, Fukumoto A, Miura A, Honma R, Satoh R, Wakamatsu A, Yamamoto J, Kimura K, Nishikawa T, Andoh T, Iida Y, Ishikawa K, Ito E, Kagawa N, Kaminaga C, Kanehori K, Kawakami B, Kenmochi K, Kimura R, Kobayashi M, Kuroita T, Kuwayama H, Maruyama Y, Matsuo K, Minami K, Mitsubori M, Mori M, Morishita R, Murase A, Nishikawa A, Nishikawa S, Okamoto T, Sakagami N, Sakamoto Y, Sasaki Y, Seki T, Sono S, Sugiyama A, Sumiya T, Takayama T, Takayama Y, Takeda H, Togashi T, Yahata K, Yamada H, Yanagisawa Y, Endo Y, Imamoto F, Kisu Y, Tanaka S, Isogai T, Imai J, Watanabe S, Nomura N: Human protein factory for converting the transcriptome into an in vitro-expressed proteome,. Nat Methods. 2008 Dec;5(12):1011-7. 19054851
  5. Heilig R, Eckenberg R, Petit JL, Fonknechten N, Da Silva C, Cattolico L, Levy M, Barbe V, de Berardinis V, Ureta-Vidal A, Pelletier E, Vico V, Anthouard V, Rowen L, Madan A, Qin S, Sun H, Du H, Pepin K, Artiguenave F, Robert C, Cruaud C, Bruls T, Jaillon O, Friedlander L, Samson G, Brottier P, Cure S, Segurens B, Aniere F, Samain S, Crespeau H, Abbasi N, Aiach N, Boscus D, Dickhoff R, Dors M, Dubois I, Friedman C, Gouyvenoux M, James R, Madan A, Mairey-Estrada B, Mangenot S, Martins N, Menard M, Oztas S, Ratcliffe A, Shaffer T, Trask B, Vacherie B, Bellemere C, Belser C, Besnard-Gonnet M, Bartol-Mavel D, Boutard M, Briez-Silla S, Combette S, Dufosse-Laurent V, Ferron C, Lechaplais C, Louesse C, Muselet D, Magdelenat G, Pateau E, Petit E, Sirvain-Trukniewicz P, Trybou A, Vega-Czarny N, Bataille E, Bluet E, Bordelais I, Dubois M, Dumont C, Guerin T, Haffray S, Hammadi R, Muanga J, Pellouin V, Robert D, Wunderle E, Gauguet G, Roy A, Sainte-Marthe L, Verdier J, Verdier-Discala C, Hillier L, Fulton L, McPherson J, Matsuda F, Wilson R, Scarpelli C, Gyapay G, Wincker P, Saurin W, Quetier F, Waterston R, Hood L, Weissenbach J: The DNA sequence and analysis of human chromosome 14. Nature. 2003 Feb 6;421(6923):601-7. Epub 2003 Jan 1. 12508121
  6. 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
  7. Lin X, Duan X, Liang YY, Su Y, Wrighton KH, Long J, Hu M, Davis CM, Wang J, Brunicardi FC, Shi Y, Chen YG, Meng A, Feng XH: PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling. Cell. 2006 Jun 2;125(5):915-28. 16751101
  8. Sun W, Yu Y, Dotti G, Shen T, Tan X, Savoldo B, Pass AK, Chu M, Zhang D, Lu X, Fu S, Lin X, Yang J: PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha-induced IKKbeta-NF-kappaB activation. Cell Signal. 2009 Jan;21(1):95-102. doi: 10.1016/j.cellsig.2008.09.012. Epub 2008 Oct 1. 18930133
  9. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  10. Suzuki T, Moriya K, Nagatoshi K, Ota Y, Ezure T, Ando E, Tsunasawa S, Utsumi T: Strategy for comprehensive identification of human N-myristoylated proteins using an insect cell-free protein synthesis system. Proteomics. 2010 May;10(9):1780-93. doi: 10.1002/pmic.200900783. 20213681
  11. 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
  12. 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
  13. 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
  14. Thinon E, Serwa RA, Broncel M, Brannigan JA, Brassat U, Wright MH, Heal WP, Wilkinson AJ, Mann DJ, Tate EW: Global profiling of co- and post-translationally N-myristoylated proteomes in human cells. Nat Commun. 2014 Sep 26;5:4919. doi: 10.1038/ncomms5919. 25255805
  15. Das AK, Helps NR, Cohen PT, Barford D: Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution. EMBO J. 1996 Dec 16;15(24):6798-809. 9003755