The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase dephosphorylates, and negatively regulates the activities of, MAP kinases and MAP kinase kinases. It has been shown to inhibit the activation of p38 and JNK kinase cascades induced by environmental stresses. This phosphatase can also dephosphorylate cyclin-dependent kinases, and thus may be involved in cell cycle control. Overexpression of this phosphatase is reported to activate the expression of the tumor suppressor gene TP53/p53, which leads to G2/M cell cycle arrest and apoptosis. Three alternatively spliced transcript variants encoding two distinct isoforms have been described.[6]
Interactionsedit
PPM1A has been shown to interact with Metabotropic glutamate receptor 3.[7] In 2006, Dr. Feng found that PPM1A can terminate TGF-beta signaling by inactivating Smad3 via dephosphorylation. Smad3 is an essential component of the TGF-beta signalling pathway.
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000100614 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000021096 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Mann DJ, Campbell DG, McGowan CH, Cohen PT (February 1992). "Mammalian protein serine/threonine phosphatase 2C: cDNA cloning and comparative analysis of amino acid sequences". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1130 (1): 100–4. doi:10.1016/0167-4781(92)90471-b. PMID 1311954.
^Flajolet M, Rakhilin S, Wang H, Starkova N, Nuangchamnong N, Nairn AC, Greengard P (December 2003). "Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3". Proceedings of the National Academy of Sciences of the United States of America. 100 (26): 16006–11. Bibcode:2003PNAS..10016006F. doi:10.1073/pnas.2136600100. PMC307683. PMID 14663150.
Further readingedit
Redpath NT, Price NT, Severinov KV, Proud CG (April 1993). "Regulation of elongation factor-2 by multisite phosphorylation". European Journal of Biochemistry. 213 (2): 689–99. doi:10.1111/j.1432-1033.1993.tb17809.x. PMID 8386634.
Das AK, Helps NR, Cohen PT, Barford D (December 1996). "Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution". The EMBO Journal. 15 (24): 6798–809. doi:10.1002/j.1460-2075.1996.tb01071.x. PMC452505. PMID 9003755.
Takekawa M, Maeda T, Saito H (August 1998). "Protein phosphatase 2Calpha inhibits the human stress-responsive p38 and JNK MAPK pathways". The EMBO Journal. 17 (16): 4744–52. doi:10.1093/emboj/17.16.4744. PMC1170803. PMID 9707433.
Fjeld CC, Denu JM (July 1999). "Kinetic analysis of human serine/threonine protein phosphatase 2Calpha". The Journal of Biological Chemistry. 274 (29): 20336–43. doi:10.1074/jbc.274.29.20336. PMID 10400656.
Hishiya A, Ohnishi M, Tamura S, Nakamura F (September 1999). "Protein phosphatase 2C inactivates F-actin binding of human platelet moesin". The Journal of Biological Chemistry. 274 (38): 26705–12. doi:10.1074/jbc.274.38.26705. PMID 10480873.
Cheng A, Ross KE, Kaldis P, Solomon MJ (November 1999). "Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases". Genes & Development. 13 (22): 2946–57. doi:10.1101/gad.13.22.2946. PMC317162. PMID 10580002.
Strovel ET, Wu D, Sussman DJ (January 2000). "Protein phosphatase 2Calpha dephosphorylates axin and activates LEF-1-dependent transcription". The Journal of Biological Chemistry. 275 (4): 2399–403. doi:10.1074/jbc.275.4.2399. PMID 10644691.
Lifschitz-Mercer B, Sheinin Y, Ben-Meir D, Bramante-Schreiber L, Leider-Trejo L, Karby S, Smorodinsky NI, Lavi S (July 2001). "Protein phosphatase 2Calpha expression in normal human tissues: an immunohistochemical study". Histochemistry and Cell Biology. 116 (1): 31–9. doi:10.1007/s004180100291. PMID 11479720. S2CID 1692505.
Srivastava J, Goris J, Dilworth SM, Parker PJ (April 2002). "Dephosphorylation of PKCdelta by protein phosphatase 2Ac and its inhibition by nucleotides". FEBS Letters. 516 (1–3): 265–9. doi:10.1016/S0014-5793(02)02500-0. PMID 11959144.
Ofek P, Ben-Meir D, Kariv-Inbal Z, Oren M, Lavi S (April 2003). "Cell cycle regulation and p53 activation by protein phosphatase 2C alpha". The Journal of Biological Chemistry. 278 (16): 14299–305. doi:10.1074/jbc.M211699200. PMID 12514180.
Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, Doi T, Shimotohno K, Harada T, Nishida E, Hayashi H, Sugano S (May 2003). "Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways". Oncogene. 22 (21): 3307–18. doi:10.1038/sj.onc.1206406. PMID 12761501. S2CID 38880905.
Flajolet M, Rakhilin S, Wang H, Starkova N, Nuangchamnong N, Nairn AC, Greengard P (December 2003). "Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3". Proceedings of the National Academy of Sciences of the United States of America. 100 (26): 16006–11. Bibcode:2003PNAS..10016006F. doi:10.1073/pnas.2136600100. PMC307683. PMID 14663150.
Yoshizaki T, Maegawa H, Egawa K, Ugi S, Nishio Y, Imamura T, Kobayashi T, Tamura S, Olefsky JM, Kashiwagi A (May 2004). "Protein phosphatase-2C alpha as a positive regulator of insulin sensitivity through direct activation of phosphatidylinositol 3-kinase in 3T3-L1 adipocytes". The Journal of Biological Chemistry. 279 (21): 22715–26. doi:10.1074/jbc.M313745200. PMID 15016818.
Li D, Wang F, Lai M, Chen Y, Zhang JF (February 2005). "A protein phosphatase 2calpha-Ca2+ channel complex for dephosphorylation of neuronal Ca2+ channels phosphorylated by protein kinase C". The Journal of Neuroscience. 25 (8): 1914–23. doi:10.1523/JNEUROSCI.4790-04.2005. PMC6726054. PMID 15728831.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, Watanabe Y (May 2006). "Shugoshin collaborates with protein phosphatase 2A to protect cohesin". Nature. 441 (7089): 46–52. Bibcode:2006Natur.441...46K. doi:10.1038/nature04663. PMID 16541025. S2CID 4425074.
This article on a gene on human chromosome 14 is a stub. You can help Wikipedia by expanding it.
ppm1a, protein, phosphatase, enzyme, that, humans, encoded, gene, available, structurespdbortholog, search, pdbe, rcsblist, codes1a6q, 3fxj, 3fxk, 3fxl, 3fxm, 3fxo, 4ra2, 4raf, 4ragidentifiersaliases, pp2c, alpha, pp2ca, pp2calpha, protein, phosphatase, depend. Protein phosphatase 1A is an enzyme that in humans is encoded by the PPM1A gene 5 6 PPM1AAvailable structuresPDBOrtholog search PDBe RCSBList of PDB id codes1A6Q 3FXJ 3FXK 3FXL 3FXM 3FXO 4RA2 4RAF 4RAGIdentifiersAliasesPPM1A PP2C ALPHA PP2CA PP2Calpha protein phosphatase Mg2 Mn2 dependent 1AExternal IDsOMIM 606108 MGI 99878 HomoloGene 56428 GeneCards PPM1AGene location Human Chr Chromosome 14 human 1 Band14q23 1Start60 245 752 bp 1 End60 299 087 bp 1 Gene location Mouse Chr Chromosome 12 mouse 2 Band12 12 C3Start72 757 455 bp 2 End72 799 819 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inspermoocytebiceps brachiisecondary oocytejejunal mucosaamniotic fluidparotid glanddeltoid musclegastrocnemius muscleright ventricleTop expressed inmorulasubstantia nigraotic placodespermatidtriceps brachii muscledigastric musclesuperior frontal gyrussacculesternocleidomastoid muscletemporal muscleMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionR SMAD binding phosphoprotein phosphatase activity manganese ion binding protein serine threonine phosphatase activity calmodulin dependent protein phosphatase activity signal transducer activity metal ion binding catalytic activity protein binding cation binding hydrolase activity magnesium ion bindingCellular componentcytoplasm membrane nucleoplasm nucleus cytosol plasma membraneBiological processcellular response to transforming growth factor beta stimulus peptidyl threonine dephosphorylation negative regulation of SMAD protein complex assembly protein dephosphorylation negative regulation of transforming growth factor beta receptor signaling pathway Wnt signaling pathway negative regulation of transcription by RNA polymerase II negative regulation of I kappaB kinase NF kappaB signaling negative regulation of BMP signaling pathway positive regulation of protein export from nucleus positive regulation of Wnt signaling pathway positive regulation of transcription DNA templated N terminal protein myristoylation positive regulation of I kappaB kinase NF kappaB signaling dephosphorylationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez549419042EnsemblENSG00000100614ENSMUSG00000021096UniProtP35813P49443RefSeq mRNA NM 021003NM 177951NM 177952NM 008910RefSeq protein NP 066283NP 808820NP 808821NP 032936Location UCSC Chr 14 60 25 60 3 MbChr 12 72 76 72 8 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse The protein encoded by this gene is a member of the PP2C family of Ser Thr protein phosphatases PP2C family members are known to be negative regulators of cell stress response pathways This phosphatase dephosphorylates and negatively regulates the activities of MAP kinases and MAP kinase kinases It has been shown to inhibit the activation of p38 and JNK kinase cascades induced by environmental stresses This phosphatase can also dephosphorylate cyclin dependent kinases and thus may be involved in cell cycle control Overexpression of this phosphatase is reported to activate the expression of the tumor suppressor gene TP53 p53 which leads to G2 M cell cycle arrest and apoptosis Three alternatively spliced transcript variants encoding two distinct isoforms have been described 6 Interactions editPPM1A has been shown to interact with Metabotropic glutamate receptor 3 7 In 2006 Dr Feng found that PPM1A can terminate TGF beta signaling by inactivating Smad3 via dephosphorylation Smad3 is an essential component of the TGF beta signalling pathway References edit a b c GRCh38 Ensembl release 89 ENSG00000100614 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000021096 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mann DJ Campbell DG McGowan CH Cohen PT February 1992 Mammalian protein serine threonine phosphatase 2C cDNA cloning and comparative analysis of amino acid sequences Biochimica et Biophysica Acta BBA Gene Structure and Expression 1130 1 100 4 doi 10 1016 0167 4781 92 90471 b PMID 1311954 a b Entrez Gene PPM1A protein phosphatase 1A formerly 2C magnesium dependent alpha isoform Flajolet M Rakhilin S Wang H Starkova N Nuangchamnong N Nairn AC Greengard P December 2003 Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3 Proceedings of the National Academy of Sciences of the United States of America 100 26 16006 11 Bibcode 2003PNAS 10016006F doi 10 1073 pnas 2136600100 PMC 307683 PMID 14663150 Further reading editRedpath NT Price NT Severinov KV Proud CG April 1993 Regulation of elongation factor 2 by multisite phosphorylation European Journal of Biochemistry 213 2 689 99 doi 10 1111 j 1432 1033 1993 tb17809 x PMID 8386634 Das AK Helps NR Cohen PT Barford D December 1996 Crystal structure of the protein serine threonine phosphatase 2C at 2 0 A resolution The EMBO Journal 15 24 6798 809 doi 10 1002 j 1460 2075 1996 tb01071 x PMC 452505 PMID 9003755 Takekawa M Maeda T Saito H August 1998 Protein phosphatase 2Calpha inhibits the human stress responsive p38 and JNK MAPK pathways The EMBO Journal 17 16 4744 52 doi 10 1093 emboj 17 16 4744 PMC 1170803 PMID 9707433 Fjeld CC Denu JM July 1999 Kinetic analysis of human serine threonine protein phosphatase 2Calpha The Journal of Biological Chemistry 274 29 20336 43 doi 10 1074 jbc 274 29 20336 PMID 10400656 Hishiya A Ohnishi M Tamura S Nakamura F September 1999 Protein phosphatase 2C inactivates F actin binding of human platelet moesin The Journal of Biological Chemistry 274 38 26705 12 doi 10 1074 jbc 274 38 26705 PMID 10480873 Cheng A Ross KE Kaldis P Solomon MJ November 1999 Dephosphorylation of cyclin dependent kinases by type 2C protein phosphatases Genes amp Development 13 22 2946 57 doi 10 1101 gad 13 22 2946 PMC 317162 PMID 10580002 Strovel ET Wu D Sussman DJ January 2000 Protein phosphatase 2Calpha dephosphorylates axin and activates LEF 1 dependent transcription The Journal of Biological Chemistry 275 4 2399 403 doi 10 1074 jbc 275 4 2399 PMID 10644691 Lifschitz Mercer B Sheinin Y Ben Meir D Bramante Schreiber L Leider Trejo L Karby S Smorodinsky NI Lavi S July 2001 Protein phosphatase 2Calpha expression in normal human tissues an immunohistochemical study Histochemistry and Cell Biology 116 1 31 9 doi 10 1007 s004180100291 PMID 11479720 S2CID 1692505 Srivastava J Goris J Dilworth SM Parker PJ April 2002 Dephosphorylation of PKCdelta by protein phosphatase 2Ac and its inhibition by nucleotides FEBS Letters 516 1 3 265 9 doi 10 1016 S0014 5793 02 02500 0 PMID 11959144 Ofek P Ben Meir D Kariv Inbal Z Oren M Lavi S April 2003 Cell cycle regulation and p53 activation by protein phosphatase 2C alpha The Journal of Biological Chemistry 278 16 14299 305 doi 10 1074 jbc M211699200 PMID 12514180 Matsuda A Suzuki Y Honda G Muramatsu S Matsuzaki O Nagano Y Doi T Shimotohno K Harada T Nishida E Hayashi H Sugano S May 2003 Large scale identification and characterization of human genes that activate NF kappaB and MAPK signaling pathways Oncogene 22 21 3307 18 doi 10 1038 sj onc 1206406 PMID 12761501 S2CID 38880905 Flajolet M Rakhilin S Wang H Starkova N Nuangchamnong N Nairn AC Greengard P December 2003 Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3 Proceedings of the National Academy of Sciences of the United States of America 100 26 16006 11 Bibcode 2003PNAS 10016006F doi 10 1073 pnas 2136600100 PMC 307683 PMID 14663150 Yoshizaki T Maegawa H Egawa K Ugi S Nishio Y Imamura T Kobayashi T Tamura S Olefsky JM Kashiwagi A May 2004 Protein phosphatase 2C alpha as a positive regulator of insulin sensitivity through direct activation of phosphatidylinositol 3 kinase in 3T3 L1 adipocytes The Journal of Biological Chemistry 279 21 22715 26 doi 10 1074 jbc M313745200 PMID 15016818 Li D Wang F Lai M Chen Y Zhang JF February 2005 A protein phosphatase 2calpha Ca2 channel complex for dephosphorylation of neuronal Ca2 channels phosphorylated by protein kinase C The Journal of Neuroscience 25 8 1914 23 doi 10 1523 JNEUROSCI 4790 04 2005 PMC 6726054 PMID 15728831 Rual JF Venkatesan K Hao T Hirozane Kishikawa T Dricot A Li N Berriz GF Gibbons FD Dreze M Ayivi Guedehoussou N Klitgord N Simon C Boxem M Milstein S Rosenberg J Goldberg DS Zhang LV Wong SL Franklin G Li S Albala JS Lim J Fraughton C Llamosas E Cevik S Bex C Lamesch P Sikorski RS Vandenhaute J Zoghbi HY Smolyar A Bosak S Sequerra R Doucette Stamm L Cusick ME Hill DE Roth FP Vidal M October 2005 Towards a proteome scale map of the human protein protein interaction network Nature 437 7062 1173 8 Bibcode 2005Natur 437 1173R doi 10 1038 nature04209 PMID 16189514 S2CID 4427026 Kitajima TS Sakuno T Ishiguro K Iemura S Natsume T Kawashima SA Watanabe Y May 2006 Shugoshin collaborates with protein phosphatase 2A to protect cohesin Nature 441 7089 46 52 Bibcode 2006Natur 441 46K doi 10 1038 nature04663 PMID 16541025 S2CID 4425074 nbsp This article on a gene on human chromosome 14 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title PPM1A amp oldid 1191568960, wikipedia, wiki, book, books, library,
