9f6p

Structural highlights

Disease

NRAM1_HUMAN Cystic fibrosis;Tuberculosis.

Function

NRAM1_HUMAN Macrophage-specific antiporter that fluxes metal ions in either direction against a proton gradient. Localized to late endosomal lysosomal membranes, delivers bivalent cations from the cytosol into these acidic compartments where they may directly affect antimicrobial activity (PubMed:11237855). Involved in iron metabolism and host natural resistance to infection with intracellular parasites. Pathogen resistance involves sequestration of Fe(2+) and Mn(2+), cofactors of both prokaryotic and eukaryotic catalases and superoxide dismutases, not only to protect the macrophage against its own generation of reactive oxygen species, but to deny the cations to the pathogen for synthesis of its protective enzymes (Probable).^{[1] [2] [3]}

References

1. ↑ Goswami T, Bhattacharjee A, Babal P, Searle S, Moore E, Li M, Blackwell JM. Natural-resistance-associated macrophage protein 1 is an H+/bivalent cation antiporter. Biochem J. 2001 Mar 15;354(Pt 3):511-9. PMID:11237855 doi:10.1042/0264-6021:3540511
2. ↑ Malik S, Abel L, Tooker H, Poon A, Simkin L, Girard M, Adams GJ, Starke JR, Smith KC, Graviss EA, Musser JM, Schurr E. Alleles of the NRAMP1 gene are risk factors for pediatric tuberculosis disease. Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12183-8. PMID:16103355 doi:10.1073/pnas.0503368102
3. ↑ Stienstra Y, van der Werf TS, Oosterom E, Nolte IM, van der Graaf WT, Etuaful S, Raghunathan PL, Whitney EA, Ampadu EO, Asamoa K, Klutse EY, te Meerman GJ, Tappero JW, Ashford DA, van der Steege G. Susceptibility to Buruli ulcer is associated with the SLC11A1 (NRAMP1) D543N polymorphism. Genes Immun. 2006 Apr;7(3):185-9. PMID:16395392 doi:10.1038/sj.gene.6364281