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SLC11A2 Membrane Protein Introduction

Introduction of SLC11A2

Solute carrier family 11 member 2 (SLC11A2), also known as divalent metal transporter 1 (DMT1) or divalent cation transporter 1 (DCT1), is a protein that in humans is encoded by the SLC11A2 gene. SLC11A2 represents a large family of orthologous metal ion transporter proteins that are highly conserved from bacteria to humans. SLC11A2 can bind with a variety of divalent metals including cadmium (Cd2+), copper (Cu2+), and zinc (Zn2+), and it is best known for its role in transporting ferrous iron (Fe2+). SLC11A2 expression is regulated by body iron stores to maintain iron homeostasis. SLC11A2 is also important in the absorption and transport of manganese (Mn2+). It is located on the apical membrane of enterocytes in digestive tract, where it carries out H+ coupled transport of divalent metal cations from the intestinal lumen into the cell.

Basic Information of SLC11A2
Protein Name Natural resistance-associated macrophage protein 2
Gene Name SLC11A2
Aliases Divalent cation transporter 1, Divalent metal transporter 1(DMT-1), Solute carrier family 11 member 2
Organism Homo sapiens (Human)
UniProt ID P49281
Transmembrane Times 12
Length (aa) 568
Sequence MVLGPEQKMSDDSVSGDHGESASLGNINPAYSNPSLSQSPGDSEEYFATYFNEKISIPEEEYSCFSFRKLWAFTGPGFLMSIAYLDPGNIESDLQSGAVAGFKLLWILLLATLVGLLLQRLAARLGVVTGLHLAEVCHRQYPKVPRVILWLMVELAIIGSDMQEVIGSAIAINLLSVGRIPLWGGVLITIADTFVFLFLDKYGLRKLEAFFGFLITIMALTFGYEYVTVKPSQSQVLKGMFVPSCSGCRTPQIEQAVGIVGAVIMPHNMYLHSALVKSRQVNRNNKQEVREANKYFFIESCIALFVSFIINVFVVSVFAEAFFGKTNEQVVEVCTNTSSPHAGLFPKDNSTLAVDIYKGGVVLGCYFGPAALYIWAVGILAAGQSSTMTGTYSGQFVMEGFLNLKWSRFARVVLTRSIAIIPTLLVAVFQDVEHLTGMNDFLNVLQSLQLPFALIPILTFTSLRPVMSDFANGLGWRIAGGILVLIICSINMYFVVVYVRDLGHVALYVVAAVVSVAYLGFVFYLGWQCLIALGMSFLDCGHTCHLGLTAQPELYLLNTMDADSLVSR

Function of SLC11A2 Membrane Protein

Toxic accumulation of divalent metal has an influence on a variety of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. SLC11A2 is the major transporter of manganese across the blood brain barrier. This protein in the nasal epithelium provides a route for direct absorption of metals into the brain. SLC11A2 expression in the brain may increase with age, increasing susceptibility to metal-induced pathologies. SLC11A2 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.

SLC11A2 Membrane Protein Introduction

Application of SLC11A2 Membrane Protein in Literature

  1. Gunshin H. Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver. J Clin Invest. 2005, 115(5):1258-66. PubMed ID: 15849611

    The authors inactivate the murine gene that encodes SLC11A2. The fetal Slc11a2 is not necessary for materno-fetal iron transfer but that Slc11a2 activity is essential for intestinal non-heme iron absorption after birth. Slc11a2 is also required for normal hemoglobin production during the development of erythroid precursors.

  2. Lam-Yuk-Tseung S., et al. Distinct targeting and recycling properties of two isoforms of the iron transporter DMT1 (NRAMP2, Slc11A2). Biochemistry. 2006, 45(7):2294-301. PubMed ID: 16475818

    This article indicates that alternative splicing of DMT1 exerts a role in the regulation of the subcellular localization and site of Fe(2+) transport.

  3. Lam-Yuk-Tseung S., et al. A novel R416C mutation in human DMT1 (SLC11A2) displays pleiotropic effects on function and causes microcytic anemia and hepatic iron overload. Blood Cells Mol Dis. 2006, 36(3):347-54. PubMed ID: 16584902

    In this article, authors propose that DMT1(C1246T) (R416C) displays a complete loss-of-function, and the decreased DMT1 expression may lead to the microcytic anemia and iron overload in the patient.

  4. Priwitzerova M., et al. Functional consequences of the human DMT1 (SLC11A2) mutation on protein expression and iron uptake. Blood. 2005, 106(12):3985-7. PubMed ID: 16091455

    In this article, authors hypothesize that the iron uptake activity of DMT1 in the patient's erythroid cells is severely inhibited because of the quantitative reduction of DMT1.

SLC11A2 Preparation Options

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