Genomic organization of human myristoyl-CoA : protein N-myristoyltransferase-1

Myristoylation is a biochemical modification of proteins in which the lipid myristate becomes covalently bound to various cellular, viral, and oncopro teins catalyzed by a monomeric enzyme myristoyl-CoA:protein N-myristoyltran sferase (NMT). This modification is important for the biological activity o f several proteins, especially the regulation of several oncoproteins invol ved in various types of cancers. Complementary DNA encoding human NMT-1 (hN MT-1) has been previously reported; however, the genomic organization of hN MT-1 has not been available. Attempts to amplify genomic fragments correspo nding to hNMT-1 cDNA sequence yielded only one fragment, We have searched d atabases using both the cDNA and sequence of one of the intron sequence and this identified a human BAC clone sequence from chromosome 17. Alignment o f hNMT-1 cDNA coding information on human chromosome 17 resulted in the com plete structural identity of 23,960 bp of the hNMT-1 gene. The hNMT-1 gene is composed of 11 exons and 10 introns with consensus GT/AG boundaries. Fin ally, we show that 140 bp from the 5' end of recently reported full-length cDNA of hNMT-1 was not part of this genomic region raising the possibility for posttranscriptional modification in generating larger transcripts likel y by trans splicing. Further, the availability of this genomic sequence wil l assist in unraveling the molecular basis for several observed NMT isoform s. (C) 1999 Academic Press.