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Gene Review

METAP1  -  methionyl aminopeptidase 1

Homo sapiens

Synonyms: KIAA0094, MAP 1, MAP1A, MetAP 1, MetAP1A, ...
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Disease relevance of METAP1

  • These findings suggest that there are two cobalt-dependent MetAP families, presently composed of the prokaryote and yeast sequences (and represented by the E. coli structure) (type I), on the one hand, and by human MetAP, the yeast open reading frame, and the partial prokaryotic sequence (type II), on the other [1].
  • The 1.15A crystal structure of the Staphylococcus aureus methionyl-aminopeptidase and complexes with triazole based inhibitors [2].
  • We demonstrate that the Salmonella typhimurium methionine aminopeptidase is totally inactive on an N-formyl-methionyl peptide in vitro, and present a detailed characterization of the substrate specificity of this key enzyme by use of a very sensitive and quantitative assay [3].
  • These results have demonstrated the possibility of developing MetAP inhibitors as antibacterial agents with minimum human toxicity [4].
  • Antisera against different Ehrlichiae recognize an immunodominant, cross-reacting approximately 28 kDa surface antigen defined as the MAP1 in Cowdria ruminantium [5].

High impact information on METAP1

  • Fumagillin-based drugs inhibit MetAP-2 but not MetAP-1, and the three-dimensional structure also indicates the likely determinants of this specificity [6].
  • Methionine aminopeptidase-1: the MAP of the mitochondrion [7]?
  • In addition, the linkage of tau and MAP1 turnover with the state of microtubule polymerization amplifies any change in their rate of synthesis, since tau and MAP1 promote microtubule polymerization [8].
  • We have found that contrary to previous suggestions, the major MAPs of adult brain, MAP1 and MAP2, are minor components of PC12 cells [9].
  • Nerve growth factor induces neurite process formation in pheochromacytoma (PC12) cells and causes the parallel increase in levels of the microtubule-associated proteins, tau and MAP1, as well as increases in tubulin levels [8].

Chemical compound and disease context of METAP1

  • The combination of these data suggests that the in vivo metal ions for the MetAP enzyme from E. coli are likely Fe(II) ions [10].

Biological context of METAP1

  • However, human MetAP was found to be much more similar to a yeast open reading frame that differed markedly from the previously reported yeast MetAP [1].
  • The C-terminal portion representing the catalytic domain shows limited identity with MetAP sequences from various prokaryotes and yeast, while the N terminus is rich in charged amino acids, including extended strings of basic and acidic residues [1].
  • The most potent of these compounds contained a singly-substituted triazole moiety which exhibited an IC50 of 8 nM (95% confidence limits 5 to 13 nM) and was highly selective for MetAP-2 over MetAP-1 (approximately 60-fold difference in IC50 values) [11].
  • Comparison of the Type I enzyme with the previously reported complex of ovalicin with Type II MetAP shows that the active site of the former is reduced in size and would incur steric clashes with the bound inhibitor [12].
  • The dependence of cell growth on methionine aminopeptidase (MetAP) function in bacteria and yeast is firmly established [13].

Anatomical context of METAP1

  • Both drug-sensitive and drug-insensitive cell lines express MetAP1 and MetAP2, indicating that drug sensitivity in mammalian cells is not simply due to the absence of compensating MetAP activity [14].
  • The degradation of tau, MAP1, and both tubulin polypeptides, however, are stimulated by microtubule depolymerization caused by colchicine, or nerve growth factor removal [8].
  • In contrast MAP1, which is characteristic of mature neurons, does not increase during PC12 cell differentiation [9].
  • High expression of methionine aminopeptidase type 2 in germinal center B cells and their neoplastic counterparts [15].
  • Our observations suggest that MAP1 B-phos plays an important role in regeneration processes in the central nervous system (CNS) of the fish [16].

Associations of METAP1 with chemical compounds


Physical interactions of METAP1


Other interactions of METAP1


Analytical, diagnostic and therapeutic context of METAP1

  • To study this in greater detail, MAP1.2 in PC12 cell lysates was resolved by SDS-PAGE in gels containing 3.25% acrylamide/4 M urea and identified by comigration with material immunoprecipitated from the lysates by MAP1 antibodies [25].
  • Immunofluorescence for MAP-1 occurred in the supporting cells of the cristae and maculae interpreted to be localized in the apical region adjacent to the sensory cells [26].


  1. Eukaryotic methionyl aminopeptidases: two classes of cobalt-dependent enzymes. Arfin, S.M., Kendall, R.L., Hall, L., Weaver, L.H., Stewart, A.E., Matthews, B.W., Bradshaw, R.A. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  2. The 1.15A crystal structure of the Staphylococcus aureus methionyl-aminopeptidase and complexes with triazole based inhibitors. Oefner, C., Douangamath, A., D'Arcy, A., Häfeli, S., Mareque, D., Mac Sweeney, A., Padilla, J., Pierau, S., Schulz, H., Thormann, M., Wadman, S., Dale, G.E. J. Mol. Biol. (2003) [Pubmed]
  3. Processing of the N termini of nascent polypeptide chains requires deformylation prior to methionine removal. Solbiati, J., Chapman-Smith, A., Miller, J.L., Miller, C.G., Cronan, J.E. J. Mol. Biol. (1999) [Pubmed]
  4. Characterization of full length and truncated type I human methionine aminopeptidases expressed from Escherichia coli. Li, J.Y., Chen, L.L., Cui, Y.M., Luo, Q.L., Gu, M., Nan, F.J., Ye, Q.Z. Biochemistry (2004) [Pubmed]
  5. Molecular characterization of a 28 kDa surface antigen gene family of the tribe Ehrlichiae. Reddy, G.R., Sulsona, C.R., Barbet, A.F., Mahan, S.M., Burridge, M.J., Alleman, A.R. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  6. Structure of human methionine aminopeptidase-2 complexed with fumagillin. Liu, S., Widom, J., Kemp, C.W., Crews, C.M., Clardy, J. Science (1998) [Pubmed]
  7. Methionine aminopeptidase-1: the MAP of the mitochondrion? Keeling, P.J., Doolittle, W.F. Trends Biochem. Sci. (1996) [Pubmed]
  8. Regulation of microtubule protein levels during cellular morphogenesis in nerve growth factor-treated PC12 cells. Drubin, D., Kobayashi, S., Kellogg, D., Kirschner, M. J. Cell Biol. (1988) [Pubmed]
  9. PC12 cells express juvenile microtubule-associated proteins during nerve growth factor-induced neurite outgrowth. Brugg, B., Matus, A. J. Cell Biol. (1988) [Pubmed]
  10. The methionyl aminopeptidase from Escherichia coli can function as an iron(II) enzyme. D'souza, V.M., Holz, R.C. Biochemistry (1999) [Pubmed]
  11. Small molecule inhibitors of methionine aminopeptidase type 2 (MetAP-2). Garrabrant, T., Tuman, R.W., Ludovici, D., Tominovich, R., Simoneaux, R.L., Galemmo, R.A., Johnson, D.L. Angiogenesis (2004) [Pubmed]
  12. Structural basis for the functional differences between type I and type II human methionine aminopeptidases. Addlagatta, A., Hu, X., Liu, J.O., Matthews, B.W. Biochemistry (2005) [Pubmed]
  13. Methionine aminopeptidases type I and type II are essential to control cell proliferation. Bernier, S.G., Taghizadeh, N., Thompson, C.D., Westlin, W.F., Hannig, G. J. Cell. Biochem. (2005) [Pubmed]
  14. Selective inhibition of amino-terminal methionine processing by TNP-470 and ovalicin in endothelial cells. Turk, B.E., Griffith, E.C., Wolf, S., Biemann, K., Chang, Y.H., Liu, J.O. Chem. Biol. (1999) [Pubmed]
  15. High expression of methionine aminopeptidase type 2 in germinal center B cells and their neoplastic counterparts. Kanno, T., Endo, H., Takeuchi, K., Morishita, Y., Fukayama, M., Mori, S. Lab. Invest. (2002) [Pubmed]
  16. The phosphorylated isoform of microtubule associated protein 1B (MAP1B) is expressed in the visual system of the tench (Tinca tinca, L) during optic nerve regeneration. Vecino, E., Ulloa, L., Avila, J. Neurosci. Lett. (1998) [Pubmed]
  17. Human methionine aminopeptidase type 2 in complex with L- and D-methionine. Nonato, M.C., Widom, J., Clardy, J. Bioorg. Med. Chem. Lett. (2006) [Pubmed]
  18. Methionine aminopeptidase 2 is a new target for the metastasis-associated protein, S100A4. Endo, H., Takenaga, K., Kanno, T., Satoh, H., Mori, S. J. Biol. Chem. (2002) [Pubmed]
  19. A single amino acid residue defines the difference in ovalicin sensitivity between type I and II methionine aminopeptidases. Brdlik, C.M., Crews, C.M. J. Biol. Chem. (2004) [Pubmed]
  20. Two continuous spectrophotometric assays for methionine aminopeptidase. Zhou, Y., Guo, X.C., Yi, T., Yoshimoto, T., Pei, D. Anal. Biochem. (2000) [Pubmed]
  21. The human spiral ganglion. Anniko, M., Arnold, W., Stigbrand, T., Ström, A. ORL J. Otorhinolaryngol. Relat. Spec. (1995) [Pubmed]
  22. Human extravillous trophoblasts express laeverin, a novel protein that belongs to membrane-bound gluzincin metallopeptidases. Fujiwara, H., Higuchi, T., Yamada, S., Hirano, T., Sato, Y., Nishioka, Y., Yoshioka, S., Tatsumi, K., Ueda, M., Maeda, M., Fujii, S. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  23. Expression of soluble human beta-globin chains in bacteria and assembly in vitro with alpha-globin chains. Yamaguchi, T., Pang, J., Reddy, K.S., Witkowska, H.E., Surrey, S., Adachi, K. J. Biol. Chem. (1996) [Pubmed]
  24. A new approach to the design of uniquely folded thermally stable proteins. Jiang, X., Farid, H., Pistor, E., Farid, R.S. Protein Sci. (2000) [Pubmed]
  25. Nerve growth factor regulates both the phosphorylation and steady-state levels of microtubule-associated protein 1.2 (MAP1.2). Aletta, J.M., Lewis, S.A., Cowan, N.J., Greene, L.A. J. Cell Biol. (1988) [Pubmed]
  26. Microtubule-associated proteins in adult human sensory organs. Anniko, M., Arnold, W. ORL J. Otorhinolaryngol. Relat. Spec. (1995) [Pubmed]
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