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

Abstract

Several lines of independent evidence suggest that human Natural Resistance Associated Macrophage Protein 1 gene (NRAMP1) is an important regulator of susceptibility to infectious diseases caused by certain intracellular pathogens. Here, we report the nucleotide sequence of 32198 bp of genomic DNA overlapping NRAMP1 on chromosomal region 2q35. The NRAMP1 gene spans 13604 bp. The gene and its 5′ genomic region are highly enriched for DNA repeat sequences. A second gene was identified in the immediate vicinity of NRAMP1 and was tentatively named Nuclear LIM Interactor-Interacting Factor (NLI-IF) by analogy to its closest ortholog. The human NLI-IF gene begins 4721 bp downstream of the NRAMP1 stop codon and is composed of seven exons varying in size from 57 bp to 1644 bp. The gene gives rise to a 2655-bp mRNA transcript that contains a 783-bp open reading frame. The predicted molecular weight 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, including consensus binding sequences for Sp1, AP-2, NF-kappa B, and PU 1. The NLI-IF amino acid sequence has homology to proteins that have a high degree 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 four related proteins of unknown function. Northern 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 transcript with estimated size of 7 kb was expressed only in the placenta. Our data 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.