CLONING AND CHARACTERIZATION OF A 2ND HUMAN NRAMP GENE ON CHROMOSOME-12Q13

The mouse Nramp1 gene was initially identified by positional cloning as a candidate for the host resistance locus Beg on mouse Chromosome (Chr) 1. Subsequent studies have shown that Nramp is a small gene family of at least three members in the mouse genome. We report the isolation and characterization of a cDNA clone corresponding to the second member of the human NRAMP family, NRAMP2. Predicted amino acid sequence analysis of the NRAMP2 polypeptide identifies a polytopic membrane protein highly homologous to NRAMP1, with 66% identical residues (80% overall homology), resulting in identical predicted secondary structures for the two proteins. Sequence conservation is particularly high in the predicted transmembrane domains (90%), suggesting that these regions play a key role in the structural and functional aspects common to both proteins. As opposed to its NRAMP1 counterpart, whose expression is restricted to phagocytic cells, Northern blotting analyses indicate that NRAMP2 mRNA transcripts are expressed at low levels in all tissues analyzed. Fluorescence in situ hybridization has identified 12q13 as the chromosomal location for human NRAMP2.