Human natural resistance-associated macrophage protein: cDNA cloning, chromosomal mapping, genomic organization, and tissue-specific expression.

• DOI: 10.1084/jem.180.5.1741
• Publication Date: 2004-06-24T07:56:10Z
• Authors: M Cellier; G Govoni; S Vidal; T Kwan; N Groulx; J Liu; F Sanchez; E Skamene; E Schurr; P Gros
• Keywords: genomic DNA

Natural resistance to infection with unrelated intracellular parasites such as Mycobacteria, Salmonella, and Leishmania is controlled in the mouse by a single gene on chromosome 1, designated Bcg, Ity, or Lsh. A candidate for natural resistance-associated macrophage protein (Nramp), has been isolated shown encode novel macrophage-specific membrane protein, which altered susceptible animals. We have cloned characterized cDNA clones corresponding human NRAMP gene. Nucleotide predicted amino acid sequence analyses indicate that polypeptide encodes 550-amino residue 10-12 putative transmembrane domains, two N-linked glycosylation sites, an evolutionary conserved consensus transport motif. Identification of genomic indicates maps 2q35 within group syntenic loci proximal 1. The composed at least 15 exons, several exons encoding discrete structural domains protein. These studies also identified alternatively spliced exon encoded Alu element present intron 4. Although this was found expressed vivo, it would introduce termination codon downstream V, resulting severely truncated Northern blot mRNA expression tightly tissue-specific fashion, highest sites being peripheral blood leukocytes, lungs, spleen. Additional RNA cultured cells site indicated increased correlated advanced state differentiation lineage.