Complete nucleotide sequence and genomic structure of the human NRAMP1 gene region on Chromosome region 2q35

Several lines of independent evidence suggest that human Natural Resistance Associated Macrophage Protein I gene (NRAMP1) is an important regulator of susceptibility to infectious diseases caused by certain intracellular path ogens. Here, we report the nucleotide sequence of 32198 bp of genomic DNA o verlapping NRAMP1 on chromosomal region 2q35. The NRAMP1 gene spans 13604 b p. The gene and its 5' genomic region are highly enriched for DNA repeat se quences. A second gene was identified in the immediate vicinity of NRAMP1 a nd was tentatively named Nuclear LIM Interactor-Interacting Factor (NLI-IF) by analogy to its closest ortholog. The human NLI-IF gene begins 4721 bp d ownstream of the NRAMP1 stop codon and is composed of seven exons varying i n size from 57 bp to 1644 bp. The gene gives rise to a 2655-bp, mRNA transc ript that contains a 783-bp open leading frame. The predicted molecular wei ght of the 261-amino acid NLI-IF protein is 29.2 kDa. Several putative gene regulatory elements were identified in the 5' upstream region of NLI-IF, i ncluding consensus binding sequences fur Sp]. AP-2, NF-kappa B, and PU 1. T he NLI-IF amino acid sequence has homology to proteins that have a high deg ree of homology with the NLI-interacting factor from Gallus gallus and are found in divergent species ranging from yeast to plants. NLI-IF is part of a human gene family encoding foul related proteins of unknown function. Nor thern blot analysis of 15 different human tissues revealed a 2.6-kb NLI-IF mRNA that was ubiquitously expressed, but at varying levels. A second trans cript with estimated size of 7 kb was expressed only in the placenta. Our d ata provide new sequence information about the NRAMP1 gene region that will be useful in the search for genetic variants causally involved in altered susceptibility to infectious diseases.