nm23 -H4, a new member of the family of human nm23 /nucleoside diphosphate kinase genes localised on chromosome 16p13

Abstract

A novel human nm23/nucleoside diphosphate (NDP) kinase gene, called nm23-H4, was identified by screening a human stomach cDNA library with a probe generated by amplification by reverse transcription-polymerase chain reaction. The primers were designed from publicly available database cDNA sequences selected according to their homology to the human nn23-H1 putative metastasis suppressor gene. The full-length cDNA sequence predicts a 187 amino acid protein possessing the region homologous to NDP kinases with all residues crucial for nucleotide binding and catalysis, strongly suggesting that Nm23-H4 possesses NDP kinase activity. It shares 56, 55 and 60% identity with Nm23-H1, Nm23-H2 and DR-Nm23, respectively, the other human Nm23 proteins isolated so far. Compared with these proteins, Nm23-H4 contains an additional NH2-terminal region that is rich in positively charged residues and could indicate routing to mitochondria. The nm23-H4 gene has been localised to human chromosomal band 16p13.3. The corresponding 1.2 kb mRNA is widely distributed and expressed in a tissue-dependent manner, being found at very high levels in prostate, heart, liver, small intestine and skeletal muscle tissues and in low amounts in the brain and in blood leucocytes. Nm23-H4 naturally possesses the Pro-Ser substitution equivalent to the K-pn mutation (P97S) of Drosophila.

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

“…The product of the third gene, DR-nm23, inhibits granulocyte differentiation and induces apoptosis of 32Dc13 myeloid cells (5). The nm23-H4 gene was identified in our laboratory (6), and the Nm23-H4 protein, the object of the present study, possesses characteristics for mitochondrial targeting. Recently, we also identified another nm23 homologous gene, nm23-H5, specifically expressed in testis germinal cells (7).…”

“…The K-pn mutation substitutes a serine for a proline in a surface loop, named for this reason the K-pn loop, that makes subunit contacts in the hexamer and plays an important part in the stability of the hexamers (17,18). The proline residue is conserved in most NDP kinases, but it is a serine in Nm23-H4 (6) and in the NDP kinase of pigeon liver mitochondria (19).…”

Single Strand DNA Specificity Analysis of Human Nucleoside Diphosphate Kinase B

“…In human cells, four members of the NDP kinase family encoded by the genes nm23-H 1 (8), nm23-H 2 (9), DR-nm23 (10), and nm23-H 4 (11) have been identified so far. A fifth isoform, nm23-H 5 was isolated very recently but it does not exhibit NDP kinase activity when overexpressed in bacteria (12).…”

Elevated plasma level of differentiation inhibitory factor nm23-H1 protein correlates with risk factors for myelodysplastic syndrome

“…[10][11][12][13][14][15][16] The nm23 proteins are involved in tumor metastasis regulation and have nucleoside diphosphate kinase enzyme activity that catalyzes the ATP-dependent synthesis of nucleoside diphosphates. [17][18][19][20][21][22][23][24] The expression of nm23-H1 has been reported to have an inverse relationship with metastatic potential and in various malignancies. 18 The inhibition of differentiation may be associated with the aggressive behavior of leukemia.…”