DMT1/SLC11A2 Antibody [C16J1] Datasheet

Biological Description

Specificity	DMT1/SLC11A2 Antibody [C16J1] detects endogenous levels of total DMT1/SLC11A2 protein.
Background	DMT1 (SLC11A2/NRAMP2) is a proton‑coupled divalent metal transporter of the SLC11 family that provides the major route for non‑heme iron entry into enterocytes and for transferrin‑derived iron exit from endosomes in erythroid precursors and other cells, thereby linking luminal, endosomal, and cytosolic iron pools to systemic iron homeostasis and intracellular metal balance. The polytopic transporter spans the membrane with multiple transmembrane helices that form a substrate translocation pathway and couple inward movement of Fe²⁺ and other divalent cations to the proton gradient, operating on the apical brush‑border membrane of duodenal enterocytes to import Fe²⁺ released from dietary sources and on endosomal membranes in erythroblasts to move Fe²⁺ from acidified transferrin‑containing endosomes into the cytosol for heme synthesis. Four main DMT1 isoforms arise from alternative promoter usage and 3′ UTR splicing, differing in N‑terminal sequence and presence or absence of an iron‑responsive element (IRE) in the 3′ UTR; these isoforms show distinct tissue and subcellular distributions and are differentially regulated by systemic iron status via HIF2α‑dependent transcription and IRE/IRP‑mediated post‑transcriptional control, allowing DMT1 expression to increase in iron deficiency and decrease when iron stores are replete. Functionally, DMT1 is selective for divalent cations and transports Fe²⁺ with high preference but also mediates uptake of Mn²⁺, Co²⁺, Cd²⁺, and other metals, which makes it central not only to physiological iron absorption and erythropoiesis but also to manganese handling and potential accumulation of toxic metals under environmental or therapeutic exposure. Biallelic loss‑of‑function mutations in SLC11A2 cause an ultra‑rare hypochromic microcytic anemia with iron overload (AHMIO1), where impaired DMT1 activity in erythroblasts reduces endosomal iron delivery to the cytosol, producing iron‑restricted erythropoiesis despite high serum iron, while compensatory upregulation of intestinal DMT1 and continued iron absorption promote hepatic iron overload, leading to anemia with paradoxically elevated serum iron and liver dysfunction. Missense mutations such as G75R and N491S impair DMT1 trafficking and stability, causing mislocalization to lysosomes, reduced transporter levels in patient lymphoblasts, and diminished Fe²⁺ transport, and clinical reports indicate that recombinant erythropoietin can improve the anemic phenotype and may help mobilize hepatic iron in such patients, making SLC11A2 a mechanistically informative genetic cause of combined anemia and iron overload. In the nervous system, DMT1 expression is detected in dopaminergic neurons of the substantia nigra, and the IRE‑containing isoform (DMT1+IRE) is upregulated in toxin‑based Parkinson’s disease models and in postmortem PD nigra, where increased DMT1 correlates with elevated nigral iron, enhanced Fe²⁺ uptake, reactive oxygen species generation, and oxidative stress; iron chelation attenuates these effects, supporting a pathogenic role for DMT1‑mediated iron accumulation in nigral neurodegeneration.

Specificity

DMT1/SLC11A2 Antibody [C16J1] detects endogenous levels of total DMT1/SLC11A2 protein.

Background

DMT1 (SLC11A2/NRAMP2) is a proton‑coupled divalent metal transporter of the SLC11 family that provides the major route for non‑heme iron entry into enterocytes and for transferrin‑derived iron exit from endosomes in erythroid precursors and other cells, thereby linking luminal, endosomal, and cytosolic iron pools to systemic iron homeostasis and intracellular metal balance. The polytopic transporter spans the membrane with multiple transmembrane helices that form a substrate translocation pathway and couple inward movement of Fe²⁺ and other divalent cations to the proton gradient, operating on the apical brush‑border membrane of duodenal enterocytes to import Fe²⁺ released from dietary sources and on endosomal membranes in erythroblasts to move Fe²⁺ from acidified transferrin‑containing endosomes into the cytosol for heme synthesis. Four main DMT1 isoforms arise from alternative promoter usage and 3′ UTR splicing, differing in N‑terminal sequence and presence or absence of an iron‑responsive element (IRE) in the 3′ UTR; these isoforms show distinct tissue and subcellular distributions and are differentially regulated by systemic iron status via HIF2α‑dependent transcription and IRE/IRP‑mediated post‑transcriptional control, allowing DMT1 expression to increase in iron deficiency and decrease when iron stores are replete. Functionally, DMT1 is selective for divalent cations and transports Fe²⁺ with high preference but also mediates uptake of Mn²⁺, Co²⁺, Cd²⁺, and other metals, which makes it central not only to physiological iron absorption and erythropoiesis but also to manganese handling and potential accumulation of toxic metals under environmental or therapeutic exposure. Biallelic loss‑of‑function mutations in SLC11A2 cause an ultra‑rare hypochromic microcytic anemia with iron overload (AHMIO1), where impaired DMT1 activity in erythroblasts reduces endosomal iron delivery to the cytosol, producing iron‑restricted erythropoiesis despite high serum iron, while compensatory upregulation of intestinal DMT1 and continued iron absorption promote hepatic iron overload, leading to anemia with paradoxically elevated serum iron and liver dysfunction. Missense mutations such as G75R and N491S impair DMT1 trafficking and stability, causing mislocalization to lysosomes, reduced transporter levels in patient lymphoblasts, and diminished Fe²⁺ transport, and clinical reports indicate that recombinant erythropoietin can improve the anemic phenotype and may help mobilize hepatic iron in such patients, making SLC11A2 a mechanistically informative genetic cause of combined anemia and iron overload. In the nervous system, DMT1 expression is detected in dopaminergic neurons of the substantia nigra, and the IRE‑containing isoform (DMT1+IRE) is upregulated in toxin‑based Parkinson’s disease models and in postmortem PD nigra, where increased DMT1 correlates with elevated nigral iron, enhanced Fe²⁺ uptake, reactive oxygen species generation, and oxidative stress; iron chelation attenuates these effects, supporting a pathogenic role for DMT1‑mediated iron accumulation in nigral neurodegeneration.

Usage Information

Application

WB, IP

Dilution

WB	IP
1:1000	1:50

Reactivity

Human

Source

Rabbit Monoclonal Antibody

MW

62 kDa

Storage Buffer

PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage
(from the date of receipt)

-20°C (avoid freeze-thaw cycles), 2 years

References

https://pubmed.ncbi.nlm.nih.gov/20357807/
https://pubmed.ncbi.nlm.nih.gov/19011085/

DMT1/SLC11A2 Antibody [C16J1]

Biological Description

Usage Information

References

Application Data