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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
The family of proton-coupled metal ion transporters are responsible for movements of divalent cations, particularly ferrous and manganese ions, across the cell membrane (SLC11A2/DMT1) and across endosomal (SLC11A2/DMT1) or lysosomal/phagosomal membranes (SLC11A1/NRAMP1), dependent on proton transport. Both proteins appear to have 12 TM regions and cytoplasmic N- and C- termini. NRAMP1 is involved in antimicrobial action in macrophages, although its precise mechanism is undefined. Facilitated diffusion of divalent cations into phagosomes may increase intravesicular free radicals to damage the pathogen. Alternatively, export of divalent cations from the phagosome may deprive the pathogen of essential enzyme cofactors. SLC11A1/DMT1 is more widely expressed and appears to assist in divalent cation assimilation from the diet, as well as in phagocytotic cells.
* Key recommended reading is highlighted with an asterisk
* Codazzi F, Pelizzoni I, Zacchetti D, Grohovaz F. (2015) Iron entry in neurons and astrocytes: a link with synaptic activity. Front Mol Neurosci, 8: 18. [PMID:26089776]
* Li X, Yang Y, Zhou F, Zhang Y, Lu H, Jin Q, Gao L. (2011) SLC11A1 (NRAMP1) polymorphisms and tuberculosis susceptibility: updated systematic review and meta-analysis. PLoS ONE, 6 (1): e15831. [PMID:21283567]
* Mackenzie B, Hediger MA. (2004) SLC11 family of H+-coupled metal-ion transporters NRAMP1 and DMT1. Pflugers Arch., 447 (5): 571-9. [PMID:14530973]
* Montalbetti N, Simonin A, Kovacs G, Hediger MA. (2013) Mammalian iron transporters: families SLC11 and SLC40. Mol. Aspects Med., 34 (2-3): 270-87. [PMID:23506870]
* Nevo Y, Nelson N. (2006) The NRAMP family of metal-ion transporters. Biochim. Biophys. Acta, 1763 (7): 609-20. [PMID:16908340]
* Skjørringe T, Burkhart A, Johnsen KB, Moos T. (2015) Divalent metal transporter 1 (DMT1) in the brain: implications for a role in iron transport at the blood-brain barrier, and neuronal and glial pathology. Front Mol Neurosci, 8: 19. [PMID:26106291]
* Wessling-Resnick M. (2015) Nramp1 and Other Transporters Involved in Metal Withholding during Infection. J. Biol. Chem., 290 (31): 18984-90. [PMID:26055722]
* Zheng W, Monnot AD. (2012) Regulation of brain iron and copper homeostasis by brain barrier systems: implication in neurodegenerative diseases. Pharmacol. Ther., 133 (2): 177-88. [PMID:22115751]
1. Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA. (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature, 388 (6641): 482-8. [PMID:9242408]
2. Zhang Z, Kodumuru V, Sviridov S, Liu S, Chafeev M, Chowdhury S, Chakka N, Sun J, Gauthier SJ, Mattice M et al.. (2012) Discovery of benzylisothioureas as potent divalent metal transporter 1 (DMT1) inhibitors. Bioorg. Med. Chem. Lett., 22 (15): 5108-13. [PMID:22749870]
Database page citation:
SLC11 family of proton-coupled metal ion transporters. Accessed on 23/03/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=183.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Transporters. Br J Pharmacol. 172: 6110-6202.