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Important in metal transport, in particular iron. Can also transport manganese, cobalt, cadmium, nickel, vanadium and lead. Involved in apical iron uptake into duodenal enterocytes. Involved in iron transport from acidified endosomes into the cytoplasm of erythroid precursor cells. May play an important role in hepatic iron accumulation and tissue iron distribution. May serve to import iron into the mitochondria.
Gene References into Functions
DMT1 was increased in myelodysplastic syndrome patients. PMID: 28714470
SLC11A2 expression is increased in the intestine of patients with type 2 diabetes in association with iron stores and serum hepcidin levels. PMID: 29082606
Results indicate that there is a dysregulation of DMT1 + IRE in IA testes, which might due to the up-regulation of IRP1 and HIF-1A. PMID: 28762519
celiac disease may unmask the contribution of the DMT1 IVS4+44C>A polymorphism to the risk of anemia. PMID: 29023457
These results suggest that the increased expression of DMT1 induces iron overload and iron overload induces osteoblast autophagy and apoptosis, thus affecting the pathological processes of osteoporosis. Clarifying the mechanisms underlying the effects of DMT1 will allow the identification of novel targets for the prevention and treatment of osteoporosis. PMID: 28367088
the cellular iron importer, divalent metal transporter 1 (DMT1), is highly expressed in colorectal cancer through hypoxia-inducible factor 2alpha-dependent transcription. PMID: 27546461
Divalent metal transporter-1 overexpression in endometriosis patients' endometrium can increase iron influx to endometrial cells, inducing oxidative stress-mediated proinflammatory signaling. In turn, endometriosis-related conditions, as iron overload and inflammation (IL-1beta), enhance endometriosis patients endometrial DMT1 expression, creating a vicious circle on DMT-1-modulated pathways. PMID: 27117373
X-ray crystallographic analysis of a 4-component complex comprising the VPS26 & VPS35 subunits of retromer, sorting nexin SNX3, & recycling signal from the divalent cation transporter DMT1-II; analysis identifies a binding site for canonical recycling signals at the interface between VPS26 & SNX3; shows cooperative interactions among the VPS subunits, SNX3 & cargo that couple signal-recognition to membrane recruitment. PMID: 27889239
Gene silencing of either CTR1 or DMT1 did not affect copper accumulation in cells, but deficiency in both CTR1 and DMT1 resulted in a complete inhibition of copper uptake. PMID: 26067577
These data suggest that iron uptake induces the production of ROS, which modify DMT1 endocytic cycling, thus changing the iron transport activity at the apical membrane. PMID: 26289753
We propose that DMT1 deficiency negatively affects metabolism and life span of mature erythrocytes; two other aspects of defective erythropoiesis which contribute to the pathophysiology of the disease PMID: 25562168
the TT genotype and T allele of the 1254T>C polymorphism may be a risk factor for Parkinson disease PMID: 25817364
Suggest role for divalent cation transporter DMT1 in the entry of Hg(II) into the intestinal epithelium. PMID: 25772431
Six months after RYGB surgery, patients exhibit an increase in DMT1 expression in the enterocytes of the tips of the villi at the proximal jejunum PMID: 24914374
In Parkinson's disease, increased iron levels are associated with increased Ndfip1 expression for the regulation of DMT1, including abnormal Ndfip1 activation in non-neuronal cell types such as astrocytes. PMID: 24475238
The DMT1 IVS4 C(+) allele occurred more frequently in WND than in the healthy controls. PMID: 24120082
DMT1 not only exports iron from endosomes, but also serves to import the metal into the mitochondria PMID: 24448823
Manganese (Mn) transport carriers DMT1 and FPN1 mediate the apical uptake and basolateral exit of Mn in colonic epithelial Caco-2 cells. PMID: 23996061
DMT1 is likely involved in endosomal iron transport in placental STB and placental DMT1 + IRE expression was primarily regulated by the IRE/IRP mechanism PMID: 21947861
Identification and characterization of the first SLC11A2 isoform 1a mutation causing a defect in splicing process and an hypomorphic allele expression of the SLC11A2 gene. PMID: 23016933
Data suggest that DMT-1 in enterocytes is delocalized from plasma membrane upon iron or zinc depletion; apical abundance of DMT-1 increases with zinc supplementation. PMID: 22137264
sequenced exons and exon-intron boundaries of SLC11A2 and TMPRSS6 in all 6 family members with iron-refractory iron deficiency anaemia; cannot exclude or confirm a gene-gene interaction between SLC11A2 and TMPRSS6; gene sequencing did not reveal causative rare mutations PMID: 22509377
Substrate profile and metal-ion selectivity of human divalent metal-ion transporter-1. PMID: 22736759
that 1B/(-)IRE DMT1 expression and intracellular iron influx are early downstream responses to NF-kappaB/RelA activation and acetylation during brain ischemia and contribute to the pathogenesis of stroke-induced neuronal damage PMID: 22666436
DMT1 regulation in an isoform specific fashion can occur by ubiquitination and the events involved have implications for DMT1 function and disease processes. PMID: 22310887
These results suggest that the VS4+44C>A polymorphism of the DMT1 gene may interact with place of living and gender to modulate the risk of age-related macular degeneration (AMD). PMID: 22371024
Data show that both shRNA-DMT1 and shRNA-hCTR1 cells had lower apical Fe uptake, Cu uptake, and Zn content compared to control cells. PMID: 22068728
analysis of synthesis and biological evaluation of substituted pyrazoles as blockers of divalent metal transporter 1 (DMT1) PMID: 22154351
The data were consistent with PAP7 interacting with DMT1 and regulating DMT1 expression in K562 cells by modulating expression of DMT1 protein. PMID: 22383495
CC haplotype in DMT1 gene is a possible risk factor for Parkinson disease in this Han Chinese population. PMID: 21777657
Our data confirm the major role of SLC11A2 in the maintenance of iron homeostasis in humans and demonstrate that the mutation contributes to the development of anemia and hepatic iron overload. PMID: 21871825
Homology implies that inverted structural symmetry facilitates Slc11 H(+)-driven Me(2+) import and provides a 3D framework to test structure-activity relationships in macrophages and study functional evolution of MntH/Nramp (Slc11) carriers. PMID: 21948377
Data show that the peptide can bind to Mn2+ and Co2+ ions by the side chains of the negatively charged residues in the motif and the C-terminal part of DMT1-TMD1. PMID: 21074515
Our findings support an implication for iron metabolism in amyotrophic lateral sclerosis and suggest that the genotype of the SLC11A2 gene could modulate the duration of the disease PMID: 21276595
An acute increase in hepcidin concentration reduces intestinal iron absorption through ubiquitin-dependent proteasome degradation of DMT1 PMID: 21199652
Data suggest that miR-Let-7d participates in the finely tuned regulation of iron metabolism by targeting DMT1-IRE isoform in erythroid cells. PMID: 20410187
Findings demonstrate that the retromer recognizes the recycling signal of DMT1-II and ensures its proper endosomal recycling. PMID: 20164305
Ca2+ is a low-affinity noncompetitive inhibitor--but not a transported substrate--of DMT1, explaining in part the effect of high dietary calcium on iron bioavailability. PMID: 20152801
Suggest a novel mechanism of regulation of intestinal iron absorption based on inward and outward fluxes at both membrane domains, and repositioning of DMT1 and FPN between membrane and intracellular compartments as a function of iron supply. PMID: 20007457
These findings suggest both that DMT1 plays a critical role in ion-mediated neuropathogenesis in Alzheimer's disease (AD) and that pharmacological blockage of DMT1 may provide novel therapeutic strategies against AD. PMID: 19679638
location was observed on or near the cell surface suggesting it might participate in surface membrane transport of iron PMID: 11891802
expression levels of human DCT1 mRNA, and to a lesser extent IREG1 mRNA, are regulated in an iron-dependent manner PMID: 11897618
airway epithelial cells increase mRNA and expression of the Nramp2/DMT1/DCT1 without an IRE after exposure to iron. The increase results in an elevated transport of iron and its probable detoxification by these cells. PMID: 11943663
iron regulation of DMT1 involves the expression of a previously unrecognized upstream 5' exon (exon 1A) of the human and murine DMT1 gene PMID: 12209011
Using the Xenopus oocyte expression system, human Nramp2, a human intestinal iron transporter, was shown to work as a cadmium transporter PMID: 12662899
These results demonstrate that DMT1 is a physiologically relevant Cu(1+) transporter in intestinal cells, indicating that intestinal absorption of copper and iron are intertwined. PMID: 12734107
in iron deficiency DMT-1 and mobilferrin concentrated in apical surface of duodenal villae; increase due to increased binding to mucin in vesicles near surfacel; localized in goblet cells and outside cell in luminal mucin PMID: 12949888
divalent metal ion transporter-1 may be of pivotal importance for the regulation of metal ion homeostasis within organs involved in absorption and excretion of ions PMID: 12973678
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Involvement in disease
Anemia, hypochromic microcytic, with iron overload 1 (AHMIO1)
Ubiquitously expressed. Isoform 1 is highly expressed in brain. Isoform 2 is highly expressed in spleen, thymus and pancreas. Isoform 3 and isoform 4 are abundantly expressed in duodenum and kidney.