Alternative titles; symbols
HGNC Approved Gene Symbol: NMT1
Cytogenetic location: 17q21.31 Genomic coordinates (GRCh38): 17:45,061,317-45,109,016 (from NCBI)
Myristate, a rare 14-carbon saturated fatty acid, is cotranslationally attached by an amide linkage to the N-terminal glycine residue of cellular and viral proteins with diverse functions. N-myristoyltransferase (NMT; EC 2.3.1.97) catalyzes the transfer of myristate from CoA to proteins. N-myristoylation appears to be irreversible and is required for full expression of the biologic activities of several N-myristoylated proteins, including the alpha subunit of the signal-transducing guanine nucleotide-binding protein (G protein) GO (GNAO1; 139311) (Duronio et al., 1992).
Insertional mutagenesis of the Nmt1 gene in Saccharomyces cerevisiae causes recessive lethality, indicating that N-myristoylation provides an essential function for one or more of the approximately 12 proteins of this yeast that are substrates for Nmt1. Duronio et al. (1992) isolated cDNAs encoding human NMT by complementing a point mutation of this gene in Saccharomyces cerevisiae that causes temperature-sensitive myristic acid auxotrophy. Human NMT is encoded by a single-copy gene, contains 416 amino acids, and is 44% identical to the yeast NMT.
Giang and Cravatt (1998) identified human and mouse cDNAs encoding NMT1 and NMT2 (603801). The predicted 496-amino acid human NMT1 protein shares 77% and 97% sequence identity with human NMT2 and mouse Nmt1, respectively. Western analysis revealed that there are 4 isoforms of NMT1 with apparent molecular masses ranging from 49 to 68 kD. In cell fractionation studies, the 68-kD NMT1 isoform and NMT2 were present in both membrane and cytoplasmic fractions, while the smaller NMT1 isoforms were predominantly cytoplasmic. The authors suggested that the membranous NMTs may reflect the association of these cotranslational processing proteins with ribosomes that are themselves bound to membranes. Northern blot analysis showed that both NMT1 and NMT2 were expressed in most human and mouse tissues.
Gross (2014) mapped the NMT1 gene to chromosome 17q21.31 based on an alignment of the NMT1 sequence (GenBank AF020500) with the genomic sequence (GRCh37).
Giang and Cravatt (1998) found that both NMT1 and NMT2 myristoylated several commonly studied peptide substrates with similar, but distinguishable, relative selectivities when expressed in mammalian cells.
In intercrosses of Nmt1 +/- mice, Yang et al. (2005) obtained no viable Nmt1 -/- pups, and Nmt1 +/- pups were born at less than predicted frequency. Nmt1 -/- embryos died between embryonic days 3.5 and 7.5. Stem cells developed from Nmt1 -/- embryos yielded small embryoid bodies in in vitro differentiation experiments and did not contribute normally to organogenesis in chimeric mice, indicating that they were functionally abnormal. Nmt2 expression was lower during early embryonic development than at later time points, and total Nmt activity levels were reduced by about 95% in Nmt1 -/- embryonic stem cells. Yang et al. (2005) concluded that NMT1 is the principal N-methyltransferase in early embryogenesis, and that NMT2 is unlikely to rescue NMT1 deficiency.
Duronio, R. J., Reed, S. I., Gordon, J. I. Mutations of human myristoyl-CoA:protein N-myristoyltransferase cause temperature-sensitive myristic acid auxotrophy in Saccharomyces cerevisiae. Proc. Nat. Acad. Sci. 89: 4129-4133, 1992. [PubMed: 1570339] [Full Text: https://doi.org/10.1073/pnas.89.9.4129]
Giang, D. K., Cravatt, B. F. A second mammalian N-myristoyltransferase. J. Biol. Chem. 273: 6595-6598, 1998. [PubMed: 9506952] [Full Text: https://doi.org/10.1074/jbc.273.12.6595]
Gross, M. B. Personal Communication. Baltimore, Md. 5/27/2014.
Yang, S. H., Shrivastav, A., Kosinski, C., Sharma, R. K., Chen, M.-H., Berthiaume, L. G., Peters, L. L., Chuang, P.-T., Young, S. G., Bergo, M. O. N-myristoyltransferase 1 is essential in early mouse development. J. Biol. Chem. 280: 18990-18995, 2005. [PubMed: 15753093] [Full Text: https://doi.org/10.1074/jbc.M412917200]