protein o methyltransferase


Summary: An enzyme that catalyzes the transfer of methyl groups from S-adenosylmethionine to free carboxyl groups of a protein molecule forming methyl esters. EC 2.1.1.-.

Top Publications

  1. Sato M, Yoshida T, Tuboi S. Primary structure of rat brain protein carboxyl methyltransferase deduced from cDNA sequence. Biochem Biophys Res Commun. 1989;161:342-7 pubmed
  2. Barten D, O Dea R. Protein carboxylmethyltransferase activity in intact, differentiated neuroblastoma cells: quantitation by S-[3H]adenosylmethionine prelabeling. J Neurochem. 1989;53:1156-65 pubmed
    ..5% serum treatment and that this modification is substoichiometric suggests that protein carboxyl methylation is not an essential component of the differentiation process in neuroblastoma cells. ..
  3. Castellarin S, Di Gaspero G. Transcriptional control of anthocyanin biosynthetic genes in extreme phenotypes for berry pigmentation of naturally occurring grapevines. BMC Plant Biol. 2007;7:46 pubmed
  4. Cho J, Kim S, Kwon M, Kim S, Lee H, Hong S. Protein carboxylmethylation in porcine spleen is mainly mediated by class I protein carboxyl O-methyltransferase. Arch Pharm Res. 2004;27:206-16 pubmed
    ..Therefore, our data suggest that most spleen PCM may be catalyzed by class I PCMT, which participates in repairing aged proteins. ..
  5. Ganesh L, Yoshimoto T, Moorthy N, Akahata W, Boehm M, Nabel E, et al. Protein methyltransferase 2 inhibits NF-kappaB function and promotes apoptosis. Mol Cell Biol. 2006;26:3864-74 pubmed
    ..Taken together, these data suggest that PRMT2 inhibits cell activation and promotes programmed cell death through this NF-kappaB-dependent mechanism. ..
  6. Kim B, Lee Y, Hur H, Lim Y, Ahn J. Production of three O-methhylated esculetins with Escherichia coli expressing O-methyltransferase from poplar. Biosci Biotechnol Biochem. 2006;70:1269-72 pubmed
    ..coli expressing POMT-9 generated scopoletin, isoscopoletin, and scoparone at 30.3, 21, and 31 microM respectively. POMT-9 is the first O-methyltransferase that produces three different O-methylated products. ..
  7. Magee A. Metabolic labeling of prenyl and carboxyl-methyl groups. Curr Protoc Cell Biol. 2001;Chapter 7:Unit 7.5 pubmed publisher
    ..g., farnesyl and geranylgeranyl. Carboxy-methylation often accompanies prenylation. The methyl group can be labeled using [(3)H-methyl]methionine. ..
  8. Ladino C, O Connor C. Identification of a site for carboxyl methylation in human alpha-globin. Biochem Biophys Res Commun. 1991;180:742-7 pubmed
    ..The site is located in a Staphylococcus V8 peptide containing residues 1-30 of alpha-globin. Two potential sources of methylation sites are present in this sequence at Asp-t and Asn-9. ..
  9. O Connor C, Germain B, Guthrie K, Aswad D, Millette C. Protein carboxyl methyltransferase activity specific for age-modified aspartyl residues in mouse testes and ovaries: evidence for translation during spermiogenesis. Gamete Res. 1989;22:307-19 pubmed
    ..The relatively high levels of PCMT in spermatogenic cells may be important for the extensive metabolism of proteins accompanying spermatid condensation or for the repair of damaged proteins in translationally inactive spermatozoa. ..

More Information


  1. Haklai R, Kloog Y. Purification and characterization of protein carboxyl methyltransferase from Torpedo ocellata electric organ. Biochemistry. 1987;26:4200-6 pubmed
    ..This property, as well as the relatively high molecular weight and the marked sensitivity to sulfhydryl reagents, distinguishes between the electric organ PCM and analogous enzymes of mammalian tissues. ..
  2. Ota I, Clarke S. Calcium affects the spontaneous degradation of aspartyl/asparaginyl residues in calmodulin. Biochemistry. 1989;28:4020-7 pubmed
    ..When calmodulin was incubated under the same conditions in the presence of calcium, methylation at residues in the Ca2+ binding regions was not observed.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  3. Caamaño C, Azcurra J, Sellinger O, Zand R. Kinetics of carboxylmethylation of the charge isoforms of myelin basic protein by protein methyltransferase II. J Neurochem. 1989;53:1883-8 pubmed
    ..The differences in the rates of isoform carboxylmethylation are largely accounted for by the different apparent dissociation constants Ks and is explained on the basis of inherent structural differences among the charge isoforms. ..
  4. Tilbrook P, Paterson H, Marshall C. Reversion of a human tumour cell line containing oncogenic p21ras is associated with a defect in the post-translational processing of the ras protein. Oncogene. 1995;10:805-9 pubmed
    ..This was not however due to defects in the Step I enzymes farnesyltransferase or carboxymethyltransferase whose activities were not reduced. ..
  5. Yoo Y, Watts S, Rechsteiner M. Ubiquitin-RAS peptide extensions as substrates for farnesyl-protein transferase and carboxymethyltransferase. Biochem J. 1992;285 ( Pt 1):55-60 pubmed
    ..Using this assay, we partially purified the enzyme from rabbit reticulocyte lysate. We also detected methylation of the farnesylated Ub-cRAS terminus in Xenopus egg extract. ..
  6. Syed S, Kim S, Paik W. Identification of the S-adenosyl-L-methionine binding site of protein-carboxyl O-methyltransferase using 8-azido-S-adenosyl-L-methionine. Biochemistry. 1993;32:2242-7 pubmed
    ..An important characteristic of the sequence is the presence of two adjacent aspartic acid residues (Asp117-Asp118) which most likely provide the negative charge environment for the sulfonium moiety of the AdoMet molecule. ..
  7. Li L, Popko J, Zhang X, Osakabe K, Tsai C, Joshi C, et al. A novel multifunctional O-methyltransferase implicated in a dual methylation pathway associated with lignin biosynthesis in loblolly pine. Proc Natl Acad Sci U S A. 1997;94:5461-6 pubmed
  8. Gilbert J, Fowler A, Bleibaum J, Clarke S. Purification of homologous protein carboxyl methyltransferase isozymes from human and bovine erythrocytes. Biochemistry. 1988;27:5227-33 pubmed
    ..These results suggest that the erythrocyte isozymes from both organisms may have nearly identical structures and confirm the similarities in the function of these methyltransferases that have been previously demonstrated. ..
  9. Galletti P, Ingrosso D, Manna C, Sica F, Capasso S, Pucci P, et al. Enzymatic methyl esterification of synthetic tripeptides: structural requirements of the peptide substrate. Detection of the reaction products by fast-atom-bombardment mass spectrometry. Eur J Biochem. 1988;177:233-9 pubmed
    ..By this soft ionization technique, the methyl-esterified peptides as well as the corresponding cyclic imides generated during the spontaneous demethylation process have been identified. ..
  10. Yarlett N, Quamina A, Bacchi C. Protein methylases in Trypanosoma brucei brucei: activities and response to DL-alpha-difluoromethylornithine. J Gen Microbiol. 1991;137:717-24 pubmed
    ..The possible role of the enzyme in morphological control and its potential as a chemotherapeutic target are discussed. ..
  11. Simms S, Subbaramaiah K. The kinetic mechanism of S-adenosyl-L-methionine: glutamylmethyltransferase from Salmonella typhimurium. J Biol Chem. 1991;266:12741-6 pubmed
    ..8 microM and 4.07 mg/ml total membrane protein (approximately 4.2 microM Tar protein), respectively. The Kd of AdoMet for the enzyme was 10.9 microM as determined by binding studies. ..
  12. Gingras D, Beliveau R. Guanine nucleotides stimulate carboxyl methylation of kidney cytosolic proteins. Biochim Biophys Acta. 1992;1136:150-4 pubmed
    ..These results suggest that class-II-associated protein methylation activity from the soluble fraction of the kidney can be regulated by guanine nucleotides. ..
  13. Gagnon C, Veeraragavan K, Coulombe R. Protein-carboxyl methylation in adrenal medullary cells. Cell Mol Neurobiol. 1988;8:95-103 pubmed
    ..They further suggest that methylation may occur on nascent peptide chains before they are injected into the rough endoplasmic reticulum. ..
  14. Sontag J, Nunbhakdi Craig V, Montgomery L, Arning E, Bottiglieri T, Sontag E. Folate deficiency induces in vitro and mouse brain region-specific downregulation of leucine carboxyl methyltransferase-1 and protein phosphatase 2A B(alpha) subunit expression that correlate with enhanced tau phosphorylation. J Neurosci. 2008;28:11477-87 pubmed publisher
    ..Our results suggest that counteracting the neuronal loss of LCMT-1 and B(alpha) could be beneficial for all tauopathies and folate-dependent disorders of the CNS. ..
  15. Cimato T, Tang J, Xu Y, Guarnaccia C, Herschman H, Pongor S, et al. Nerve growth factor-mediated increases in protein methylation occur predominantly at type I arginine methylation sites and involve protein arginine methyltransferase 1. J Neurosci Res. 2002;67:435-42 pubmed
    ..Finally, immunoprecipitation of PRMT1 from PC12 cells provides the first demonstration of an NGF-activated methyltransferase and implicates PRMT1 in NGF signal transduction. ..
  16. Goggins M, Scott J, Weir D. Regional differences in protein carboxymethylation in post-mortem human brain. Clin Sci (Lond). 1998;94:677-85 pubmed
    ..Post-mortem brain tissue can serve as a tool for the study of physiological or pathological factors which influence human brain protein methylation in vivo. ..
  17. Balaban C, O Callaghan J, Billingsley M. Trimethyltin-induced neuronal damage in the rat brain: comparative studies using silver degeneration stains, immunocytochemistry and immunoassay for neuronotypic and gliotypic proteins. Neuroscience. 1988;26:337-61 pubmed
  18. Stevenson C, Freel Meyers C, Walsh C, Lawson D. Crystallization and preliminary X-ray analysis of the O-methyltransferase NovP from the novobiocin-biosynthetic cluster of Streptomyces spheroides. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007;63:236-8 pubmed
    ..4 A were collected from a single crystal at the synchrotron. NovP is involved in the biosynthesis of the aminocoumarin antibiotic novobiocin that targets the essential bacterial enzyme DNA gyrase. ..
  19. Phelouzat M, Lawrence F, Moulay L, Borot C, Schaeverbeke J, Schaeverbeke M, et al. Leishmania donovani: antagonistic effect of S-adenosyl methionine on ultrastructural changes and growth inhibition induced by sinefungin. Exp Parasitol. 1992;74:177-87 pubmed
    ..Overall the results suggest that one of the main targets of sinefungin in exponentially growing cells is the protein carboxylmethylation involved in membrane transport. ..
  20. Wein M, Lavid N, Lunkenbein S, Lewinsohn E, Schwab W, Kaldenhoff R. Isolation, cloning and expression of a multifunctional O-methyltransferase capable of forming 2,5-dimethyl-4-methoxy-3(2H)-furanone, one of the key aroma compounds in strawberry fruits. Plant J. 2002;31:755-65 pubmed
    ..In addition, it is concluded that the Strawberry-OMT plays an important role in the biosynthesis of strawberry volatiles such as vanillin and DMMF...
  21. Chasman D, Adams R. Predicting the functional consequences of non-synonymous single nucleotide polymorphisms: structure-based assessment of amino acid variation. J Mol Biol. 2001;307:683-706 pubmed
    ..This estimate suggests that a typical person will have about 6240-12,800 heterozygous loci that encode proteins with functional variation due to natural amino acid polymorphism. ..
  22. Lee J, Pallas D. Leucine carboxyl methyltransferase-1 is necessary for normal progression through mitosis in mammalian cells. J Biol Chem. 2007;282:30974-84 pubmed
    ..Collectively, our results indicate that LCMT-1 is important for normal progression through mitosis and cell survival and is essential for embryonic development in mice. ..
  23. Xie H, Clarke S. Protein phosphatase 2A is reversibly modified by methyl esterification at its C-terminal leucine residue in bovine brain. J Biol Chem. 1994;269:1981-4 pubmed
    ..Because this modification reaction is readily reversible in extracts, it may represent a novel strategy of the cell to modulate the function of this protein phosphatase. ..
  24. Kopycki J, Rauh D, Chumanevich A, Neumann P, Vogt T, Stubbs M. Biochemical and structural analysis of substrate promiscuity in plant Mg2+-dependent O-methyltransferases. J Mol Biol. 2008;378:154-64 pubmed publisher
  25. Hackett S, Campochiaro P. Implication of protein carboxymethylation in retinal pigment epithelial cell chemotaxis. Ophthalmic Res. 1988;20:54-9 pubmed
    ..Migration of RPE cells has been implicated in the pathogenesis of proliferative vitreoretinopathy (PVR). Inhibition of protein carboxymethylation may provide a new target in the development of pharmacologic therapy for PVR. ..
  26. Solomon R, Katzir O, Egozi Y, Kloog Y. Identification of two distinct protein carboxyl methyltransferases in eucaryotic cells. FEBS Lett. 1988;241:131-5 pubmed
    ..The existence of at least two distinct PCMs in eucaryotic cells raises the possibility that these enzymes are involved in distinct transmethylation reactions. ..
  27. Pethe K, Bifani P, Drobecq H, Sergheraert C, Debrie A, Locht C, et al. Mycobacterial heparin-binding hemagglutinin and laminin-binding protein share antigenic methyllysines that confer resistance to proteolysis. Proc Natl Acad Sci U S A. 2002;99:10759-64 pubmed publisher
    ..This hypothesis was confirmed by the fact that HBHA produced by recombinant M. smegmatis was also methylated. These results show that mycobacteria use enzymatic methylation of lysines to ensure greater stability of their adhesins...
  28. Uson I, Stevenson C, Lawson D, Sheldrick G. Structure determination of the O-methyltransferase NovP using the 'free lunch algorithm' as implemented in SHELXE. Acta Crystallogr D Biol Crystallogr. 2007;63:1069-74 pubmed
    ..The resulting phases have a mean phase error of 17 degrees relative to a refined model. ..
  29. Metz S, Rabaglia M, Stock J, Kowluru A. Modulation of insulin secretion from normal rat islets by inhibitors of the post-translational modifications of GTP-binding proteins. Biochem J. 1993;295 ( Pt 1):31-40 pubmed
  30. Lindquist J, Barofsky E, McFadden P. Determination of two sites of automethylation in bovine erythrocyte protein (D-aspartyl/L-isoaspartyl) carboxyl methyltransferase. J Protein Chem. 1996;15:115-22 pubmed
    ..The identification of more than one site of automethylation shows that alpha PCM is not a homogeneous population of damaged PCM molecules, but rather a complex population of molecules with a variety of age-altered damage sites. ..
  31. Lee S, Cho Y. Induction of apoptosis in leukemia U937 cells by 5'-deoxy-5'-methylthioadenosine, a potent inhibitor of protein carboxylmethyltransferase. Exp Cell Res. 1998;240:282-92 pubmed
  32. Gingras D, Menard P, Beliveau R. Protein carboxyl methylation in kidney brush-border membranes. Biochim Biophys Acta. 1991;1066:261-7 pubmed
  33. Ota I, Clarke S. Enzymatic methylation of 23-29-kDa bovine retinal rod outer segment membrane proteins. Evidence for methyl ester formation at carboxyl-terminal cysteinyl residues. J Biol Chem. 1989;264:12879-84 pubmed
    ..Vogel, J. P., Deschenes, R. J., and Stock, J. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 4643-4647). ..
  34. Cooke H, Guenther E, Luo Y, Shen B, Bruner S. Molecular basis of substrate promiscuity for the SAM-dependent O-methyltransferase NcsB1, involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin. Biochemistry. 2009;48:9590-8 pubmed publisher
    ..In addition, residues important for substrate discrimination were predicted and probed through site-directed mutagenesis and in vitro biochemical characterization. ..
  35. Romanik E, O Connor C. Methylation of microinjected isoaspartyl peptides in Xenopus oocytes. Competition with protein carboxyl methylation reactions. J Biol Chem. 1989;264:14050-6 pubmed
    ..This excess capability may have physiological significance when structurally abnormal proteins accumulate as a result of cellular stress and or aging. ..
  36. Lunkenbein S, Salentijn E, Coiner H, Boone M, Krens F, Schwab W. Up- and down-regulation of Fragaria x ananassa O-methyltransferase: impacts on furanone and phenylpropanoid metabolism. J Exp Bot. 2006;57:2445-53 pubmed
    ..Thus, FaOMT is involved in at least two different biochemical pathways in ripe strawberry fruit. ..
  37. Avila J, Avila A. Correlation of sinefungin susceptibility and drug-affinity for protein carboxymethyltransferase activity in American Leishmania species. Mol Biochem Parasitol. 1987;26:69-75 pubmed
  38. Longin S, Jordens J, Martens E, Stevens I, Janssens V, Rondelez E, et al. An inactive protein phosphatase 2A population is associated with methylesterase and can be re-activated by the phosphotyrosyl phosphatase activator. Biochem J. 2004;380:111-9 pubmed
    ..We discuss a potential new function for PME-1 as an enzyme that stabilizes an inactivated pool of PP2A. ..
  39. Johnson B, Shirokawa J, Aswad D. Deamidation of calmodulin at neutral and alkaline pH: quantitative relationships between ammonia loss and the susceptibility of calmodulin to modification by protein carboxyl methyltransferase. Arch Biochem Biophys. 1989;268:276-86 pubmed
    ..A. Johnson, N. E. Freitag, and D. W. Aswad, (1985) J. Biol. Chem. 260, 10913-10916) that deamidation occurs preferentially at Asn-60 and/or Asn-97, each of which resides in a distinct Ca2+-binding domain. ..
  40. Henzel W, Bourell J, Stults J. Analysis of protein digests by capillary high-performance liquid chromatography and on-line fast atom bombardment mass spectrometry. Anal Biochem. 1990;187:228-33 pubmed
    ..Detection limits of 0.5-5 pmol are routine. Proteolytic digests of recombinant human methionyl growth hormone and protein carboxyl methyltransferase have been used to demonstrate the HPLC and mass spectrometer performance. ..
  41. Yoon H, Park H, Jhon G. GM3 affects carboxyl methylation in the human erythrocyte membrane. Biochem Int. 1992;28:393-9 pubmed
    ..Thus conformational difference of membrane according to localization of GM3 in intact human erythrocyte membrane or liposome possibly increases the methylatability and activity of glucose transporter itself. ..
  42. Longin S, Zwaenepoel K, Martens E, Louis J, Rondelez E, Goris J, et al. Spatial control of protein phosphatase 2A (de)methylation. Exp Cell Res. 2008;314:68-81 pubmed
    ..PME-1 associates with an inactive PP2A population, regardless of its esterase activity or localization. We propose that stabilization of this inactive, nuclear PP2A pool is a major in vivo function of PME-1. ..
  43. Jonczyk R, Schmidt H, Osterrieder A, Fiesselmann A, Schullehner K, Haslbeck M, et al. Elucidation of the final reactions of DIMBOA-glucoside biosynthesis in maize: characterization of Bx6 and Bx7. Plant Physiol. 2008;146:1053-63 pubmed publisher
    ..At present, Bx6 and Bx7 have no close relatives among the members of their respective gene families. Bx6 and Bx7 map to the cluster of Bx genes on the short arm of chromosome 4...
  44. Boivin D, Gingras D, Beliveau R. Purification and characterization of a membrane-bound protein carboxyl methyltransferase from rat kidney cortex. J Biol Chem. 1993;268:2610-5 pubmed
  45. Kim B, Lee Y, Hur H, Lim Y, Ahn J. Flavonoid 3'-O-methyltransferase from rice: cDNA cloning, characterization and functional expression. Phytochemistry. 2006;67:387-94 pubmed publisher
  46. Li C, Gershon P. pKa of the mRNA cap-specific 2'-O-methyltransferase catalytic lysine by HSQC NMR detection of a two-carbon probe. Biochemistry. 2006;45:907-17 pubmed
    ..5, consistent with a perturbed pKa for the catalytic lysine and a model in which the surrounding charged groups direct the lysine epsilon-amino pKa via both local electrostatic environment and orbital directionality. ..
  47. Dayan F, Kagan I, Rimando A. Elucidation of the biosynthetic pathway of the allelochemical sorgoleone using retrobiosynthetic NMR analysis. J Biol Chem. 2003;278:28607-11 pubmed
    ..The lipid resorcinol intermediate is then methylated by a S-adenosylmethionine-dependent O-methyltransferase and subsequently dihydroxylated by a P450 monooxygenase to yield the reduced form of sorgoleone. ..
  48. Drake J, Link C, Butterfield D. Oxidative stress precedes fibrillar deposition of Alzheimer's disease amyloid beta-peptide (1-42) in a transgenic Caenorhabditis elegans model. Neurobiol Aging. 2003;24:415-20 pubmed
    ..These results are discussed with reference to Alzheimer's disease. ..
  49. Saido T, Toyoshima S, Osawa T. Protein-O-carboxylmethyltransferase from cytosol and membranes of chicken erythrocytes. J Biochem. 1987;102:319-26 pubmed
    ..5 and 0.71 microM. This report deals with the biochemical differences between purified cytosolic and membrane-associated protein carboxymethylase from the same cell source. ..
  50. Ohta K, Seo N, Yoshida T, Hiraga K, Tuboi S. Tubulin and high molecular weight microtubule-associated proteins as endogenous substrates for protein carboxymethyltransferase in brain. Biochimie. 1987;69:1227-34 pubmed
  51. Li S, Anzai Y, Kinoshita K, Kato F, Sherman D. Functional analysis of MycE and MycF, two O-methyltransferases involved in the biosynthesis of mycinamicin macrolide antibiotics. Chembiochem. 2009;10:1297-301 pubmed publisher
    ..With the reconstituted in vitro assays, the order of mycinamicin VI-->III-->IV in the post-PKS (polyketide synthase) tailoring pathway of mycinamicin was unambiguously determined. ..
  52. Sellinger O, Wolfson M. Carboxylmethylation affects the proteolysis of myelin basic protein by Staphylococcus aureus V8 proteinase. Biochim Biophys Acta. 1991;1080:110-8 pubmed
    ..8, also disclose that the proteinase totally failed to recognize and hence cleave the two Glu-X bonds (Glu-82-Asn-83 and Glu-118-Gly-119) of MBP, preferring to cleave the protein at a number of hitherto unreported sites. ..
  53. Gómez García I, Stevenson C, Uson I, Freel Meyers C, Walsh C, Lawson D. The crystal structure of the novobiocin biosynthetic enzyme NovP: the first representative structure for the TylF O-methyltransferase superfamily. J Mol Biol. 2010;395:390-407 pubmed publisher
    ..These observations could inform future attempts to utilize NovP for methylating a range of glycosylated compounds. ..