DMT1

SLC11A2
Identifiers
Aliases SLC11A2, DCT1, DMT1, NRAMP2, AHMIO1, solute carrier family 11 member 2
External IDs OMIM: 600523 MGI: 1345279 HomoloGene: 55471 GeneCards: SLC11A2
RNA expression pattern




More reference expression data
Orthologs
Species Human Mouse
Entrez

4891

18174

Ensembl

ENSG00000110911

ENSMUSG00000023030

UniProt

P49281

P49282

RefSeq (mRNA)

NM_001146161
NM_008732

RefSeq (protein)

NP_001139633.1
NP_032758.2

Location (UCSC) Chr 12: 50.98 – 51.03 Mb Chr 15: 100.39 – 100.43 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/Edit Mouse

The divalent metal transporter 1 (DMT1), also known as natural resistance-associated macrophage protein 2 (NRAMP 2), and divalent cation transporter 1 (DCT1),[3] is a protein that in humans is encoded by the SLC11A2 (solute carrier family 11, member 2) gene.[4] DMT1 represents a large family of orthologous metal ion transporter proteins that are highly conserved from bacteria to humans.[5]

As its name suggests, DMT1 binds a variety of divalent metals including cadmium (Cd2+), copper (Cu2+), and zinc (Zn2+,,) however it is best known for its role in transporting ferrous iron (Fe2+); DMT1 expression is regulated by body iron stores to maintain iron homeostasis. DMT1 is also important in the absorption and transport of manganese (Mn2+).[6] In the digestive tract, it is located on the apical membrane of enterocytes, where it carries out H+ coupled transport of divalent metal cations from the intestinal lumen into the cell.

Role in neurodegenerative diseases

Toxic accumulation of divalent metals, especially iron and/or manganese, are frequently discussed aetiological factors in a variety of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. DMT1 may be the major transporter of manganese across the blood brain barrier and expression of this protein in the nasal epithelium provides a route for direct absorption of metals into the brain.[7] DMT1 expression in the brain may increase with age,[8] increasing susceptibility to metal induced pathologies. DMT1 expression is found to be increased in the substantia nigra of Parkinson's patients and in the ventral mesencephalon of animal models intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) - a neurotoxin widely used experimentally to produce Parkinsonian symptoms.

The DMT1 encoding gene SLC11A2 is located on the long arm of chromosome 12 (12q13) close to susceptibility regions for Alzheimer's disease[9] and restless legs syndrome. The C allele of SNP rs407135 on the DMT1 encoding gene SLC11A2 is associated with shorter disease duration in cases of spinal onset amyotrophic lateral sclerosis,[10] and is implicated in Alzheimer's disease onset in males as well.[9] The CC haplotype for SNPs 1254T/C IVS34+44C/A is associated with Parkinson's disease susceptibility.[11] Finally, variant alleles on several SLC11A2 SNPs are associated with iron anemia, a risk factor for manganese intoxication and restless legs syndrome.[12]

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. ↑ "Solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2". GeneCards. Retrieved 2011-12-16.
  4. ↑ Vidal S, Belouchi AM, Cellier M, Beatty B, Gros P (April 1995). "Cloning and characterization of a second human NRAMP gene on chromosome 12q13". Mamm. Genome. 6 (4): 224–30. doi:10.1007/BF00352405. PMID 7613023.
  5. ↑ Au C, Benedetto A, Aschner M (July 2008). "Manganese transport in eukaryotes: the role of DMT1". Neurotoxicology. 29 (4): 569–76. doi:10.1016/j.neuro.2008.04.022. PMC 2501114Freely accessible. PMID 18565586.
  6. ↑ Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA (July 1997). "Cloning and characterization of a mammalian proton-coupled metal-ion transporter". Nature. 388 (6641): 482–8. doi:10.1038/41343. PMID 9242408.
  7. ↑ Aschner M (May 2006). "The transport of manganese across the blood–brain barrier". Neurotoxicology. 27 (3): 311–4. doi:10.1016/j.neuro.2005.09.002. PMID 16460806.
  8. ↑ Ke Y, Chang YZ, Duan XL, Du JR, Zhu L, Wang K, Yang XD, Ho KP, Qian ZM (May 2005). "Age-dependent and iron-independent expression of two mRNA isoforms of divalent metal transporter 1 in rat brain". Neurobiol. Aging. 26 (5): 739–48. doi:10.1016/j.neurobiolaging.2004.06.002. PMID 15708449.
  9. 1 2 Jamieson SE, White JK, Howson JM, Pask R, Smith AN, Brayne C, Evans JG, Xuereb J, Cairns NJ, Rubinsztein DC, Blackwell JM (February 2005). "Candidate gene association study of solute carrier family 11a members 1 (SLC11A1) and 2 (SLC11A2) genes in Alzheimer's disease". Neurosci. Lett. 374 (2): 124–8. doi:10.1016/j.neulet.2004.10.038. PMID 15644277.
  10. ↑ Blasco H, Vourc'h P, Nadjar Y, Ribourtout B, Gordon PH, Guettard YO, Camu W, Praline J, Meininger V, Andres CR, Corcia P (April 2011). "Association between divalent metal transport 1 encoding gene (SLC11A2) and disease duration in amyotrophic lateral sclerosis". J. Neurol. Sci. 303 (1-2): 124–7. doi:10.1016/j.jns.2010.12.018. PMID 21276595.
  11. ↑ He Q, Du T, Yu X, Xie A, Song N, Kang Q, Yu J, Tan L, Xie J, Jiang H (September 2011). "DMT1 polymorphism and risk of Parkinson's disease". Neurosci. Lett. 501 (3): 128–31. doi:10.1016/j.neulet.2011.07.001. PMID 21777657.
  12. ↑ Xiong L, Dion P, Montplaisir J, Levchenko A, Thibodeau P, Karemera L, Rivière JB, St-Onge J, Gaspar C, Dubé MP, Desautels A, Turecki G, Rouleau GA (October 2007). "Molecular genetic studies of DMT1 on 12q in French-Canadian restless legs syndrome patients and families". Am. J. Med. Genet. B Neuropsychiatr. Genet. 144B (7): 911–7. doi:10.1002/ajmg.b.30528. PMID 17510944.

Further reading

External links

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