DMT1

Solute carrier family 11 (proton-coupled divalent metal ion transporter), member 2
Identifiers
Symbols	SLC11A2 ; DCT1; DMT1; NRAMP2
External IDs	OMIM: 600523 MGI: 1345279 HomoloGene: 55471 GeneCards: SLC11A2 Gene
Gene ontology Molecular function • copper ion transmembrane transporter activity • manganese ion transmembrane transporter activity • zinc ion transmembrane transporter activity • iron ion binding • copper ion binding • protein binding • zinc ion binding • hydrogen ion transmembrane transporter activity • calcium ion transmembrane transporter activity • cadmium ion transmembrane transporter activity • cobalt ion transmembrane transporter activity • ferrous iron transmembrane transporter activity • lead ion transmembrane transporter activity • nickel cation transmembrane transporter activity • vanadium ion transmembrane transporter activity • solute:proton symporter activity • ferrous iron uptake transmembrane transporter activity • nickel cation binding • inorganic cation transmembrane transporter activity • manganese ion binding • transferrin transmembrane transporter activity • cadmium ion binding • transition metal ion transmembrane transporter activity • cobalt ion binding • chromium ion transmembrane transporter activity Cellular component • nucleus • cytoplasm • mitochondrial outer membrane • lysosome • lysosomal membrane • early endosome • late endosome • vacuole • trans-Golgi network • plasma membrane • integral component of plasma membrane • brush border • cell surface • membrane • apical plasma membrane • retromer complex • cytoplasmic vesicle • late endosome membrane • apical part of cell • basal part of cell • perinuclear region of cytoplasm • recycling endosome • paraferritin complex Biological process • response to hypoxia • detection of oxygen • heme biosynthetic process • cobalt ion transport • copper ion transport • manganese ion transport • cellular copper ion homeostasis • cellular iron ion homeostasis • activation of cysteine-type endopeptidase activity involved in apoptotic process • learning or memory • response to iron ion • response to manganese ion • response to lead ion • nickel cation transport • vanadium ion transport • ferrous iron transport • lead ion transport • transferrin transport • cellular response to oxidative stress • copper ion transmembrane transport • nickel cation transmembrane transport • response to cadmium ion • dendrite morphogenesis • erythrocyte development • transmembrane transport • multicellular organismal iron ion homeostasis • cadmium ion transmembrane transport • ferrous iron import • cellular response to iron ion • cellular response to tumor necrosis factor • manganese ion transmembrane transport • cellular response to hypoxia • zinc II ion transmembrane transport • cation transmembrane transport • hydrogen ion transmembrane transport • copper ion import into cell • ferrous iron transmembrane transport Sources: Amigo / QuickGO
RNA expression pattern
File:PBB GE SLC11A2 203123 s at tn.png
File:PBB GE SLC11A2 203124 s at tn.png
File:PBB GE SLC11A2 203125 x at tn.png
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4891	18174
Ensembl	ENSG00000110911	ENSMUSG00000023030
UniProt	P49281	P49282
RefSeq (mRNA)	NM_000617	NM_001146161
RefSeq (protein)	NP_000608	NP_001139633
Location (UCSC)	Chr 12: 50.98 – 51.03 Mb	Chr 15: 100.39 – 100.43 Mb
PubMed search	[1]	[2]

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

As its name suggests, DMT1 binds a variety of divalent metals including cadmium (Cd²⁺), copper (Cu²⁺), and zinc (Zn^2+,,) 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⁺).

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. DMT1 expression in the brain may increase with age, 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 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, and is implicated in Alzheimer's disease onset in males as well. The CC haplotype for SNPs 1254T/C IVS34+44C/A is associated with Parkinson's disease susceptibility. Finally, variant alleles on several SLC11A2 SNPs are associated with iron anemia, a risk factor for manganese intoxication and restless legs syndrome.

External links

• DMT1 protein (iron transporter) at the US National Library of Medicine Medical Subject Headings (MeSH)