NME6: a new member of the nm23 /nucleoside diphosphate kinase gene family located on human chromosome 3p21.3

Abstract

The NME (nm23/nucleoside diphosphate kinase) gene family in human is involved in the phosphorylation of nucleoside diphosphates and a variety of regulatory phenomena associated with development, oncogenic transformation, and metastasis. Here we report the cDNA sequence for a sixth member of this family, NME6. The cDNA sequence predicts a 186-residue protein that includes the characteristic active site motif of a nucleoside diphosphate (NDP) kinase, as well as the other residues previously identified as crucial for nucleotide binding and catalysis. The NME6 protein sequence is only 34-41% identical to the five previously reported human NME proteins, and is similarly related to prokaryotic and primitive eukaryotic NDP kinases. Compared to typical proteins of this family such as NME1 and NME2, NME6 has three additional residues located in the Kpn loop, and a 22-residue extension at the COOH-terminal. Using radiation hybrid mapping, the NME6 gene was localized to chromosome 3p21.3. The 1.3-kb transcript of NME6 is expressed at a moderately low level in many human tissues, and is most abundant in kidney, prostate, ovary, intestine, and spleen. Homologous cDNAs were also cloned and sequenced for rat and mouse. The sequence of the first 171 residues of the mouse homologue (Nm23-M6) is 94% identical to the deduced human NME6 protein.

The Human nm23-H4 Gene Product Is a Mitochondrial Nucleoside Diphosphate Kinase

“…All have very similar three-dimensional structures, and their subunits retain a characteristic fold with five helices packed on a four-stranded antiparallel ␤-sheet (2). In humans, six nm23 genes coding for NDP kinases or for homologous isoforms have been identified: nm23-H1 (3), nm23-H2 (4), DRnm23 (5), nm23-H4 (6), nm23-H5 (7), and nm23-H6 (8). The first gene, nm23-H1, was initially identified as a putative metastasis suppressor gene (9,3).…”

“…Recently, we also identified another nm23 homologous gene, nm23-H5, specifically expressed in testis germinal cells (7). nm23-H6 is ubiquitously expressed and does not possess a specific signal sequence for organelle import or vesicular trafficking (8).…”

Characterization of Human Thioredoxin-like 2

“…1A). This is not the first report of the presence of such a repetition in a member of the NDP kinase family as nm23-H6 mRNA also harbors an Alu sequence located in the 3Ј-UTR of its mRNA (21). Interestingly, both proteins are testis-specific.…”

“…Group II encompasses nm23-H5 to H8 genes, which are defined by a more divergent sequence, including a sequence of the active site which is not strictly conserved. Furthermore, nm23-H5, H7, and H8 have been shown to have a tissue-specific distribution mainly in testis/spermatozoa (14,20,21).…”

Cloning and characterization of NM23-Bbt2 gene from amphioxus Branchiostoma belcheri tsingtauense

“…For example, slime mold Dictyostelium dicoidium and worm Caenorhabditis elegans both have three NM23 genes, fruit fly D. melanogaster has four, higher invertebrate sea squirt Ciona intestinalis has at least five related genes (Dehal et al 2002). In all vertebrates, eight related genes have been found (Steeg et al 1988b;Kimura et al 1990;Stahl et al 1991;Urano et al 1992;Shimada et al 1993;Venturelli et al 1995;Milon et al 1997;Munier et al 1998;Mehus et al 1999;Tsuiki et al 1999;Kargul et al 2000;Masse et al 2002;). It thus seemed that the number and diversity of the gene family increased in association with the complexity of the body plan, and the ancestral genes corresponding to each of vertebrates NM23 genes probably occurred before the appearance of vertebrates.…”