Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Mammalian myristoyl CoA: protein N-myristoyltransferase


Myristoyl CoA:Protein N-myristoyltransferase (NMT) is the enzyme which catalyses the covalent transfer of myristate from myristoyl CoA to the amino-terminal glycine residue of protein substrates. Although NMT is ubiquitous in eukaryotic cells, the enzyme levels and cellular distribution vary among tissues. In this article, we describe the properties of mammalian NMT(s) with reference to subcellular distribution, molecular weights, substrate specificity and the possible involvement of NMT in pathological processes. The cytosolic fraction of bovine brain contains multiple forms of NMT activity whereas bovine spleen contains only a single form. In bovine brain and spleen, the cytosol contained majority of NMT activity. In contrast, rabbit colon and rat liver NMT activity was predominantly particulate. Regional differences in NMT activity have been observed in both rabbit intestine and bovine brain. Results from our laboratory along with the existing knowledge, provide evidence for the existence of tissue specific isozymes of NMT.

This is a preview of subscription content, log in to check access.



myristoyl CoA: protein N-myristoyltransferase

NIP71 :

71 kDa heat stable N-myristoyltransferase inhibitor protein


human immunodeficiency virus 1


Moloney Murine Leukaemia virus


sodium dodecyl sulfate


  1. 1.

    Magee AI, Koyama AH, Mafler C, Wen D, Schlesinger MJ: Release of fatty acids from various glycoproteins by hydroxylamine. Biochim Biophys Acta 798: 156–166, 1984

  2. 2.

    Olson EM, Towler DA, Glaser L: Specificity of fatty acid acylation of cellular proteins. J Biol Chem 260: 3784–3790, 1985

  3. 3.

    Dunphy WG, Fries E, Urbani LJ, Rothman JE: Early and late functions associated with the Golgi apparatus reside in distinct compartments. Proc Natl Acad Sci USA 78: 7453–7457, 1981

  4. 4.

    Quinn P, Griffiths G, Warren G: Dissection of the Golgi complex II. Density separation of specific Golgi function in virally infected cells treated with monensin. J Cell Biol 96: 851–856, 1983

  5. 5.

    Schmidt MFG, Schlesinger MJ: Relation of fatty acid attachment to the translation and maturation of vesicular stomatitis and sindbis virus membrane glycoprotein. J Biol Chem 259: 3334–3339, 1980

  6. 6.

    Carr SA, Biemann K, Shoji S, Parmelee DC, Titani K:n-tetradeconyl is the NH2-terminal blocking group of the catalytic subunit of cyclic AMP dependent protein kinase from bovine cardiac muscle. Proc Natl Acad Sci USA 79: 6128–6131, 1982

  7. 7.

    Aitken A, Cohen P, Santikaran S, Williams DH, Calder AG, Smith A, Klee CB: Identification of the NH2 terminal blocking group of calcineurin B as myristic acid. FEBS Lett 150: 314–318, 1982

  8. 8.

    Schultz A, Henderson LE, Oroszlan S, Garber EA, Hanafusa H: Amino terminal myristoylation of protein kinase p60src a retroviral transforming protein. Science 227: 427–429, 1985

  9. 9.

    Boyle JJ, Ludwig EH: Analysis of fatty acids of continuously cultured mammalian cells by gas-liquid chromatography. Nature 196: 893–894, 1962

  10. 10.

    Towler DA, Gordon JI, Adams SP, Glaser L: The biology and enzymology of eukaryotic protein acylation. Annu Rev Biochem 57: 69–99, 1988

  11. 11.

    Rudnick DA, Mcwherter CA, Gokel GW, Gordon JI: Myristoyl CoA: protein N-myristoyltransferase. Adv Enzymol Relat Area Mol Biol 67: 375–430, 1993

  12. 12.

    Duronio RJ, Rudnick DA, Knoll LJ, Johnson DR, Gordon JI: N-myristoylation of proteins: Studies withSaccharomyces cerevisiae as a model system. In: M.J. Schlesinger (ed.). Lipid modification of proteins, CRC Press, London, Tokyo, pp 21–57, 1993

  13. 13.

    Grand RAJ: Acylation of viral and eukaryotic proteins. Biochem J 258: 625–628, 1989

  14. 14.

    Ozols J, Carr SA, Strittmatter P: Identification of the NH2 terminal blocking group of NADH-cytochrome b5 reductase as myristic acid and the complete amino acid sequence of the membrane-binding domain. J Biol Chem 259: 13349–13354, 1984

  15. 15.

    Marchildon GA, Casnellie JE, Walsh KA, Krebs EG: Covalently bound myristate in a lymphoma tyrosine protein kinase. Proc Natl Acad Sci USA 81: 7679–7682, 1984

  16. 16.

    Sukegawa J, Semba K, Yamanashi Y, Nishizawa M, Miyajima N, Yamamoto T, Toyoshima K: Characterization of cDNA clones for the human c-yes gene. Mol Cell Biol 7: 41–47, 1987

  17. 17.

    Semba K, Nishizawa M, Miyajima N, Yoshida MC, Sukegawa J, Yamanashi Y, Saski M, Yamamoto T, Yoyoshima K:yes-related protooncogene,syn, belongs to the protein tyrosine kinase family. Proc Natl Acad Sci USA 83: 5459–5463, 1986

  18. 18.

    Schutz AM, Tsai SC, Kung HF, Oroszlan S, Moss J, Vaughan M: Hydroxylamine-stable covalent linkage of myristic acid in Goα, a guanine nucleotide-binding protein of bovine brain. Biochem Biophys Res Commun 146: 1234–1239, 1987

  19. 19.

    Liu J, Sessa WC: Identification of covalently bound aminoterminal myristic acid in endothelial nitric oxide synthase. J Biol Chem 269: 11691–11694, 1994

  20. 20.

    Aderem AA, Albert KA, Keum Mm, Wang JKT, Greengard P, Cohn ZA: Stimulus-dependent myristoylation of a major substrate for protein kinase C. Nature 332: 362–364, 1988

  21. 21.

    Wice BM, Gordon JI: A strategy for isolation of cDNA encoding proteins affecting human intestinal epithelial cell growth and differentiation: Characterization of a novel gut-specific N-myristoylated annexin. J Cell Biol 116: 405–422, 1992

  22. 22.

    Takamatsu K, Noguchi T: Hippocalcin: a calcium-binding protein of the EF-hand superfamily dominantly expressed in the hippocampus. Neurosci Res 17: 291–294, 1993

  23. 23.

    Brown HA, Gutowski S, Moomaw CR, Slaughter C, Sternweis PC: ADP-ribosylation factor, a small GTP-dependent regulatory protein stimulates phospholipase D activity. Cell 75: 1137–1144, 1993

  24. 24.

    Van Etten RA, Jackson PK, Baltimore D, Sanders MC, Matsudaira PT, Janmey PA: The COOH terminus of the c-Abl tyrosine kinase contains distinct F-and G-actin binding domains with bundling activity. J Cell Biol 124: 325–340, 1994

  25. 25.

    Kataoka M, Mihara K, Tokunaga F: Recoverin alters its surface properties depending on both calcium-binding and N-terminal myristoylation. J Biochem (Tokyo) 114: 535–540, 1993

  26. 26.

    Kitamoto Y, Yuan X, Wu Q, McCourt DW, Sadler JE: Enterokinase, the initiator of intestinal digestion, is a mosaic protease composed of a distinctive assortment of domains. Proc Natl Acad Sci USA 91: 7588–7592, 1994

  27. 27.

    Kobayashi M, Takamatsu K, Fujishiro M, Saitoh S, Noguchi T: Molecular cloning of a novel calcium-binding protein structurally related to hippocalcin from human brain and chromosomal mapping of its gene. Biochim Biophys Acta 1222: 515–518, 1994

  28. 28.

    Maekawa S, Matsuura Y, Nakamura S: Expression and myristoylation of NAP-22 using a baculovirus transfer vector system. Biochim Biophys Acta 1218: 119–122, 1994

  29. 29.

    Pullman WE, Bodmer WF: Cloning and characterization of a gene that regulates cell adhesion. Nature 356: 529–532, 1992

  30. 30.

    Henderson LF, Krutzsch HC, Oroszlan S: Myristoyl amino-terminal acylation of murine retrovirus proteins: An unusual post translational protein modification. Proc Natl Acad Sci USA 80: 339–343, 1983

  31. 31.

    Veronese FD, Copeland TD, Oroszland S, Gallo RC, Sarangadharan MG: Biochemical and immunological analysis of human immunodeficiency virus gag gene products p17 and p24. J Virol 62: 795–801, 1988

  32. 32.

    Persing DH, Varmus HE, Ganem D: The preS1 protein of hepatitis B virus is acylated at its amino teminus with myristic acid. J Virol 61: 1672–1677, 1987

  33. 33.

    Streuli CH, Griffin BE: Myristic acid is coupled to a structural protein of polyoma virus and SV40. Nature 326: 619–622, 1987

  34. 34.

    Chow M, Newman JFE, Filman D, Hogle JM, Rowlands DJ, Brown F: Myristoylation of picornavirus capsid protein VP4 and its structural significance. Nature 327: 482–486, 1987

  35. 35.

    Buss JE, Mumby SM, Casey PJ, Gillman AG, Sefton BM: Myristoylated α-subunits of guanine nucleotide binding regulatory proteins. Proc Natl Acad Sci USA 84: 7493–7497, 1987

  36. 36.

    Rein A, McClure MR, Rice NR, Luftig RB, Schultz AM: Myristoylation site in pr65gag is essential for virus particle formation by Moloney murine leukaemia virus. Proc Natl Acad Sci USA 83: 7246–7250, 1986

  37. 37.

    Marc D, Drugeon G, Haenni AL, Girard M, Van der Werf S: Role of myristoylation of poliovirus capsid protein VP4 as determined by site directed mutagenesis of its N-terminal sequence. EMBO J 8: 2661–2668, 1989

  38. 38.

    Bryant ML, Ratner L: Myristoylation dependent replication and assembly of human immunodeficiency virus 1. Proc Natl Acad Sci USA 87: 523–527, 1990

  39. 39.

    Towler DA, Eubanks SR, Towery DS, Adams SP, Glaser L: Amino terminal processing of proteins by N-myristoylation: Substrate specificity of N-myristoyltransferase. J Biol Chem 262: 1030–1036, 1987

  40. 40.

    Kamps MP, Buss JE, Sefton BM: Mutation of NH2-terminal glycine of p60src prevents both myristoylation and morphological transformation. Proc Natl Acad Sci USA 82: 4625–4628, 1985

  41. 41.

    Kemps MP, Buss JE, Sefton BM: Rous sarcoma virus transforming protein lacking myristic acid phosphorylates known polypeptide susbstrates without inducing transformation. Cell 45: 105–112, 1986

  42. 42.

    Resh MD, Ling H: Identification of a 32K plasma membrane protein that binds to the myristoylated amino-terminal sequence of p60v-src. Nature 364: 84–86, 1990

  43. 43.

    Alland L, Peseckis SM, Atherton RE, Berthiaume L, Resh MD: Dual myristylation and palmitylation of Src family member p59fym affects subcellular localization. J Biol Chem 269: 16701–16705, 1994

  44. 44.

    Schmidt MFG: Fatty acylation of proteins. Biochim Biophys Acta 988: 411–426, 1989

  45. 45.

    Clegg CH, Ran W, Uhler MD, McKnight GS: A mutation in the catalytic subunit of protein kinase A prevents myristoylation but does not inhibit biological activity. J Biol Chem 264: 20140–20146 1989

  46. 46.

    Wiemann C, Wider G, von Freyberg B, Traber R, Braun W, Widmer H, Wuthrich K: The NMR structure of cyclosporin A bound to cyclophilin in aqueous solution. Biochemistry 30: 6563–6574, 1991

  47. 47.

    Manenti S, Sorokine O, Van Dorsselaer A, Taniguchi H: Isolation of the non-myristoylated form of a major substrate of protein kinase-C (MARCKS) from bovine brain. J Biol Chem 268: 6878–6881, 1993

  48. 48.

    McIlhinney RAJ, McGlone K: Evidence for a non-myristoylated pool of the 80 kDa protein kinase substrate of rat brain. Biochem J 271: 681–685, 1990

  49. 49.

    Towler DA, Adams SP, Eubanks SR, Towery DS, Jackson-Machelski E, Glaser L, Gordon JI: Purification and characterization of myristoyl CoA: protein N-myristoyltransferase. Proc Natl Acad Sci USA 84: 2708–2712, 1987

  50. 50.

    Duronio RJ, Towler DA, Heuckeroth RO, Gordon JI: Disruption of the yeast N-myristoyl transferase gene causes recessive lethality. Science 243: 796–800, 1989

  51. 51.

    Towler DA, Glaser L: Protein fatty acid acylation. Enzymatic synthesis of an N-myristoylglycyl peptide. Proc Natl Acad Sci USA 83: 2812–2816, 1986

  52. 52.

    Towler DA, Adams SP, Eubanks SR, Towery DS, Jackson-Machelski E, Glaser L, Gordon JI: Myristoyl CoA: protein N-myristoyl-transferase activities from rat liver and yeast possess overlapping yet distinct peptide substrate specificities. J Biol Chem 263: 1784–1790, 1988

  53. 53.

    Heuckeroth RO, Towler DA, Adams SP, Glaser L, Gordon JI: 11-(Ethylthio)undecanoic acid. A myristic acid analog of altered hydrophobicity which is functional for peptide N-myristoylation with wheat germ and yeast acyltransferase. J Biol Chem 263: 2127–2133, 1988

  54. 54.

    Boutin JA, Ferry G, Ernould AP, Maes P, Remond G, Vincent M, Atassi G: Myristoyl CoA: protein N-myristoyltransferase activity in cancer cells. Purification and characterization of a cytosolic isoform from the murine leukaemia cell line L1210. Eur J Biochem 214: 853–867, 1993

  55. 55.

    McIlhinney RAJ, McGlone K: Characterization of myristoyl CoA: glycylpeptide N-myristoyltransferase activity in rat brain: Subcellular and regional distribution. J Neurochem 54: 110–117, 1990

  56. 56.

    Glover CJ, Goddard C, Felsted RL: N-myristoylation of p60src. Biochem J 250: 485–491, 1988

  57. 57.

    King MJ, Sharma RK: N-myristoyl transferase assay using phosphocellulose paper binding. Anal Biochem 199: 149–153, 1991

  58. 58.

    King MJ, Sharma RK: Demonstration of multiple forms of bovine brain myristoyl CoA: protein N-myristoyltransferase. Mol Cell Biochem 113: 77–81, 1992

  59. 59.

    Duronio RJ, Reed SI, Gordon JI: Mutations of human myristoyl CoA: protein N-myristoyltransferase cause temperature-sensitive myristic acid auxotrophy inSaccharomyces cerevisiae. Proc Natl Acad Sci USA 89: 4129–4133, 1992

  60. 60.

    McIlhinney RAJ, McGlone K, Willis AC: Purification and partial sequencing of myristoyl CoA: protein N-myristoyltransferase from bovine brain. Biochem J 290: 405–410, 1993

  61. 61.

    Raju RVS, Kalra J, Sharma RK: Purification and properties of bovine spleen N-myristoyl CoA: protein N-myristoyltransferase. J Biol Chem 269: 12080–12083, 1994

  62. 62.

    McIlhinney RAJ, Patel PB, McGlone K: Characterization of a polyhistidine-tagged form of human myristoyl-CoA: protein N-myristoyltransferase produced inEscherichia coli. Eur J Biochem 222: 137–146, 1994

  63. 63.

    King MJ, Pugazhenthi S, Khandelwal RL, Sharma RK: Elevated N-myristoyltransferase activity is reversed by sodium orthovanadate in streptozotocin induced diabetic rat. Biochim Biophys Acta 1165: 259–262, 1993

  64. 64.

    Knoll LJ, Levy MA, Stahl PD, Gordon JI: Analysis of the compartmentalization of myristoyl CoA: protein N-myristoyltransferase inSaccharomyces cerevisiae. J Biol Chem 267: 5366–5373, 1992

  65. 65.

    Wilcox C, Hu JS, Olson EN: Acylation of proteins with myristic acid occurs cotranslationally. Science 238: 1275–1278, 1987

  66. 66.

    Magnuson BA, Raju RVS, Sharma RK: N-myristoyltransferase activity in normal rabbit intestine. Faseb J 8: A2024, 1994

  67. 67.

    King MJ, Sharma RK: Mechanisms of action of NIP71 on N-myristoyltransferase activity. Mol Cell Biochem 141: 79–86, 1994

  68. 68.

    Iozzo RV, Kovalszky I, Hacobian N, Schick PK, Ellingson JS, Dodge GR: Fatty acylation of heparin sulfate proteoglycan from human colon carcinoma cells. J Biol Chem 265: 19980–19989, 1990

  69. 69.

    Rosque WJ, McWherter CA, Wood DC, Gordon JI: A comparative analysis of the kinetic mechanism and peptide substrate specificity of human andSaccharomyces cerevisiae myristoyl CoA: protein N-myristoyltransferase. J Biol Chem 268: 9964–9971, 1993

  70. 70.

    King MJ, Sharma RK: Identification, purification and characterization of a membrane-associated N-myristoyltransferase inhibitor protein from bovine brain. Biochem J 291: 635–639, 1993

  71. 71.

    Hatefi Y, Hanstein WG: Destabilization of membranes with chaotropic ions. Methods Enzymol 31: 770–790, 1974

  72. 72.

    Davis KA, Hatefi Y: Kinetics of the resolution of complex I (Reduced Diphosphopyridine Nucleotide — Coenzyme Q Reductase) of the mitochondrial electron transport system by chaotropic agents. Biochemistry 8: 3355–3361, 1969

  73. 73.

    Holtzer A, Wang TY, Noelken ME: The effect of various monovalent anions on myosin B solutions. The identification of actin as a product of ATP action. Biochim Biophys Acta 42: 453–461, 1960

  74. 74.

    Wolff J: The effect of thyroxine on isolated dehydrogenase. J Biol Chem 237: 230–235, 1962

  75. 75.

    Cammack RR, Rao KK, Hall DO: Effect of chaotropic agents on the spectroscopic properties of spinach ferredoxin. Biochem Biophys Res Commun 44: 8–14, 1971

  76. 76.

    Gordon JA: Denaturation of globular proteins. Interaction of guanidinium salts with three proteins. Biochemistry 11: 1862–1870, 1972

  77. 77.

    Nicolau J, Bacila M: N-Acylsarcosines as inhibitors of respiration and glycolysis and glycolytic enzymes. Arch Biochem Biophys 129: 357–361, 1969

  78. 78.

    Raju RVS, King MJ, Kalra J, Sharma RK: Demonstration of two forms of myristoyl CoA: protein N-myristoyltransferase in bovine heart. Faseb J 7: A1196, 1993

  79. 79.

    Stevenson FT, Bursten SL, Loclsley RM, Lovett DH: Myristoyl acylation of the tumour necrosis factor a precursor on specific lysine residues. J Exp Med 176: 1053–1062, 1992

  80. 80.

    Muszbek L, Laposata M: Myristoylation of proteins in platelets occurs predominantly through thioester linkages. J Biol Chem 268: 8251–8255, 1993

  81. 81.

    da Silva AM, Klein CA: Rapid posttraslational myristoylation of 68 kDa protein inD. discoidedum. J Cell Biol 111: 401–407, 1990

  82. 82.

    Manenti S, Sorokine O, Dorsselaer AV, Taniguchi H: Demyristoylation of the major substrate of protein kinase C (MARCKS) by the cytoplasmic fraction of brain synaptosomes. J Biol Chem 269: 8309–8313, 1994

  83. 83.

    McIlhinney RAJ, McGlone K: A simple assay for the enzyme responsible for the attachment of myristic acid to the N-terminal glycine residue of proteins, myristoyl CoA: glycylpeptide N-myristoyltransferase. Biochem J 263: 387–391, 1989

  84. 84.

    Felsted RL, Goddard C, Glover CJ: N-myristoylation as a novel molecular target for the design of chemotherapeutic drugs. In: Cancer chemotherapy, Vol II, CRC Press Inc, pp 95–115

  85. 85.

    King MJ, Pugazhenthi S, Khandelwal RL, Sharma RK: Membrane associated N-myristoyltransferase activity is reduced in obese (fa/fa) Zucker rat liver. Biochem Biophys Res Commun 197: 665–670, 1993

  86. 86.

    Bryant ML, Heuckeroth RO, Kimata JT, Ratner L, Gordon JI: Replication of human immunodeficiency virus 1 and Moloney murine leukaemia virus is inhibited by different heteroatom containing analogs of myristic acid. Proc Natl Acad Sci USA 86: 8655–8659, 1989

  87. 87.

    Zheng GQ, Hu X, Cassady JM, Paige LA, Geahlen RL: Synthesis of myristoyl CoA analogues and myristoyl peptides as inhibitors of myristoyl CoA: protein N-myristoyltransferase. J Pharm Sci 82: 233–238, 1994

  88. 88.

    Aderem AA, Keum MM, Pure E, Cohn ZA: bacterial lipopolysaccharides, phorbol myristate acetate, and zymosan induce the myristoylation of specific macrophage proteins. Proc Natl Acad Sci USA 83: 5817–5821, 1986

  89. 89.

    Malvoisin E, Wild F, Zwingelstein G: 12-O-Tetradecanoyl phorbol 13-acetate stimulates the myristoylation of an 82 kDa protein in HL-60 cells. FEBS Lett 215: 175–178, 1987

Download references

Author information

Correspondence to Rajendra K. Sharma.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Raju, R.V.S., Magnuson, B.A. & Sharma, R.K. Mammalian myristoyl CoA: protein N-myristoyltransferase. Mol Cell Biochem 149, 191–202 (1995). https://doi.org/10.1007/BF01076577

Download citation

Key words

  • covalent modification
  • myristoyl CoA
  • myristate
  • protein myristoylation
  • N-myristoyltransferase