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Gene Review

PPM1A  -  protein phosphatase, Mg2+/Mn2+ dependent, 1A

Homo sapiens

Synonyms: MGC9201, PP2C-ALPHA, PP2C-alpha, PP2CA, PP2Calpha, ...
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Disease relevance of PPM1A


High impact information on PPM1A


Biological context of PPM1A


Anatomical context of PPM1A

  • In addition, inhibition by IC87114 of the major class IA PI3K catalytic subunit expressed in lymphocytes, p110delta, blocked transition of DN to DP cells in embryonic day 14.5 fetal thymic organ culture without affecting cell viability [14].
  • We found that the PP2C-like activity in HeLa cell extract, partially purified HeLa PP2C alpha and PP2C beta 2 isoforms, and the recombinant PP2Cs exhibited a comparable substrate preference for a phosphothreonine containing substrate, consistent with the conservation of threonine residues at the site of activating phosphorylation in CDKs [15].
  • No mRNA for PP2C alpha was detected in resting or 1,25(OH)2D3-stimulated HL-60 cells [16].
  • We showed recently that rhythmic arm movement significantly suppresses soleus H-reflex amplitude probably via modification of presynaptic inhibition of the IA afferent pathway [17].
  • Crude cord blood samples yielded three isoforms: AFP-IA, IB, and II, with pIs 4.57 (52%), 4.27 (43%), and less than 4.00 (5%), respectively [18].

Associations of PPM1A with chemical compounds

  • In this study, we have found that PPM1A, a metal ion-dependent protein serine/threonine phosphatase, physically interacts with and dephosphorylates Smad1 both in vitro and in vivo [19].
  • Hydroxyapatite chromatography further resolved the most hydrophilic, isoform I, into isoforms IA and IB [2].
  • The p85{alpha} Regulatory Subunit of Class IA Phosphoinositide 3-Kinase Regulates beta-Selection in Thymocyte Development [14].
  • Isoform IB differed from IA and III in N-terminal amino acid sequence and in sensitivity to EDTA inhibition [2].
  • Caffeine and theophylline also inhibit the intrinsic protein kinase activity of the class IA PI3Ks and DNA-dependent protein kinase, although with a much lower potency than that for the lipid kinase (IC(50) approximately 10 mm for p110 alpha, 3 mm for p110 beta, and 10 mm for DNA-dependent protein kinase) [20].

Enzymatic interactions of PPM1A


Regulatory relationships of PPM1A


Other interactions of PPM1A


Analytical, diagnostic and therapeutic context of PPM1A

  • The most hydrophobic, isoform III, differed from IA and IB by a more acidic pH optimum, greater heat resistance, greater sensitivity to alkylating agents, and anomalous retardation during gel filtration chromatography [2].
  • In order to facilitate the identification of novel and specific inhibitors of PP2C by random screening of compounds, and to further characterize this enzyme at the molecular level by site-directed mutagenesis and X-ray crystallography, we have expressed active recombinant human PP2C alpha (rPP2C alpha) in Escherichia coli [23].
  • The results of quantitative PCR analysis indicated that the expression amount of group IA genes was around 100-300 times greater than that of group IB genes [24].
  • Both mRNAs, encoding group IA (without a pancreatic loop) and group IB (with pancreatic loop), were detected from venom glands by Northern blot hybridization analysis and RT-PCR [24].
  • Sequence analysis of 5'-upstream regions and a reporter gene assay of the genes (groups IA and IB) previously cloned showed that the functional sequence (411 bp) was inserted in the 5'-flanking region of the group IA PLA(2) genes [24].


  1. Adenovirus-2 early region IA protein synthesized in Escherichia coli extracts indirectly associates with DNA. Ko, J.L., Dalie, B.L., Goldman, E., Harter, M.L. EMBO J. (1986) [Pubmed]
  2. Purification and characterization of blood group A-degrading isoforms of alpha-N-acetylgalactosaminidase from Ruminococcus torques strain IX-70. Hoskins, L.C., Boulding, E.T., Larson, G. J. Biol. Chem. (1997) [Pubmed]
  3. Routine biliary sphincterotomy may not be indispensable for endoscopic pancreatic sphincterotomy. Kim, M.H., Myung, S.J., Kim, Y.S., Kim, H.J., Seo, D.W., Nam, S.W., Ahn, J.H., Lee, S.K., Min, Y.I. Endoscopy. (1998) [Pubmed]
  4. Gs(alpha) mutations and imprinting defects in human disease. Weinstein, L.S., Chen, M., Liu, J. Ann. N. Y. Acad. Sci. (2002) [Pubmed]
  5. Liver and liver cell transplantation for glycogen storage disease type IA. Muraca, M., Burlina, A.B. Acta Gastroenterol. Belg. (2005) [Pubmed]
  6. A phosphatase controls the fate of receptor-regulated Smads. Schilling, S.H., Datto, M.B., Wang, X.F. Cell (2006) [Pubmed]
  7. PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling. Lin, X., Duan, X., Liang, Y.Y., Su, Y., Wrighton, K.H., Long, J., Hu, M., Davis, C.M., Wang, J., Brunicardi, F.C., Shi, Y., Chen, Y.G., Meng, A., Feng, X.H. Cell (2006) [Pubmed]
  8. PtdIns5P activates the host cell PI3-kinase/Akt pathway during Shigella flexneri infection. Pendaries, C., Tronchère, H., Arbibe, L., Mounier, J., Gozani, O., Cantley, L., Fry, M.J., Gaits-Iacovoni, F., Sansonetti, P.J., Payrastre, B. EMBO J. (2006) [Pubmed]
  9. Isolation of a marker linked to the Charcot-Marie-Tooth disease type IA gene by differential Alu-PCR of human chromosome 17-retaining hybrids. Patel, P.I., Garcia, C., Montes de Oca-Luna, R., Malamut, R.I., Franco, B., Slaugenhaupt, S., Chakravarti, A., Lupski, J.R. Am. J. Hum. Genet. (1990) [Pubmed]
  10. Cell cycle regulation and p53 activation by protein phosphatase 2C alpha. Ofek, P., Ben-Meir, D., Kariv-Inbal, Z., Oren, M., Lavi, S. J. Biol. Chem. (2003) [Pubmed]
  11. Glucose-potentiated chemotaxis in human vascular smooth muscle is dependent on cross-talk between the PI3K and MAPK signaling pathways. Campbell, M., Allen, W.E., Sawyer, C., Vanhaesebroeck, B., Trimble, E.R. Circ. Res. (2004) [Pubmed]
  12. Assignment of the gene encoding magnesium-dependent protein phosphatase 1alpha (PPM1A) to human chromosome 14q22-->q23 and rat chromosome 6q24 by fluorescence in situ hybridization. Saadat, M., Kikuchi, K. Cytogenet. Genome Res. (2005) [Pubmed]
  13. Sequential activation of class IB and class IA PI3K is important for the primed respiratory burst of human but not murine neutrophils. Condliffe, A.M., Davidson, K., Anderson, K.E., Ellson, C.D., Crabbe, T., Okkenhaug, K., Vanhaesebroeck, B., Turner, M., Webb, L., Wymann, M.P., Hirsch, E., Ruckle, T., Camps, M., Rommel, C., Jackson, S.P., Chilvers, E.R., Stephens, L.R., Hawkins, P.T. Blood (2005) [Pubmed]
  14. The p85{alpha} Regulatory Subunit of Class IA Phosphoinositide 3-Kinase Regulates beta-Selection in Thymocyte Development. Shiroki, F., Matsuda, S., Doi, T., Fujiwara, M., Mochizuki, Y., Kadowaki, T., Suzuki, H., Koyasu, S. J. Immunol. (2007) [Pubmed]
  15. Dephosphorylation of human cyclin-dependent kinases by protein phosphatase type 2C alpha and beta 2 isoforms. Cheng, A., Kaldis, P., Solomon, M.J. J. Biol. Chem. (2000) [Pubmed]
  16. Up-regulation of protein serine/threonine phosphatase type 2C during 1 alpha,25-dihydroxyvitamin D3-induced monocytic differentiation of leukemic HL-60 cells. Nishikawa, M., Omay, S.B., Nakai, K., Kihira, H., Kobayashi, T., Tamura, S., Shiku, H. FEBS Lett. (1995) [Pubmed]
  17. Facilitation of soleus H-reflex amplitude evoked by cutaneous nerve stimulation at the wrist is not suppressed by rhythmic arm movement. Zehr, E.P., Frigon, A., Hoogenboom, N., Collins, D.F. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (2004) [Pubmed]
  18. Chromatofocusing profile of purified human alpha-fetoprotein and albumin differs from those of crude samples: effect of protein concentration of the elution of the sample. Leal, J.A., Eddy, K.B., Keel, B.A. Anal. Biochem. (1991) [Pubmed]
  19. Protein Serine/Threonine Phosphatase PPM1A Dephosphorylates Smad1 in the Bone Morphogenetic Protein Signaling Pathway. Duan, X., Liang, Y.Y., Feng, X.H., Lin, X. J. Biol. Chem. (2006) [Pubmed]
  20. Direct effects of caffeine and theophylline on p110 delta and other phosphoinositide 3-kinases. Differential effects on lipid kinase and protein kinase activities. Foukas, L.C., Daniele, N., Ktori, C., Anderson, K.E., Jensen, J., Shepherd, P.R. J. Biol. Chem. (2002) [Pubmed]
  21. Small C-terminal Domain Phosphatases Dephosphorylate the Regulatory Linker Regions of Smad2 and Smad3 to Enhance Transforming Growth Factor-beta Signaling. Wrighton, K.H., Willis, D., Long, J., Liu, F., Lin, X., Feng, X.H. J. Biol. Chem. (2006) [Pubmed]
  22. Axin-induced apoptosis depends on the extent of its JNK activation and its ability to down-regulate beta-catenin levels. Neo, S.Y., Zhang, Y., Yaw, L.P., Li, P., Lin, S.C. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  23. Biochemical characterization and deletion analysis of recombinant human protein phosphatase 2C alpha. Marley, A.E., Sullivan, J.E., Carling, D., Abbott, W.M., Smith, G.J., Taylor, I.W., Carey, F., Beri, R.K. Biochem. J. (1996) [Pubmed]
  24. Comparative analysis of gene expression mechanisms between group IA and IB phospholipase A2 genes from sea snake Laticauda semifasciata. Fujimi, T.J., Yasuoka, S., Ogura, E., Tsuchiya, T., Tamiya, T. Gene (2004) [Pubmed]
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