MntH2

Target Synonyms and Classification: The divalent metal cation transporter MntH2 belongs to the Natural Resistance-Associated Macrophage Protein family (NRAMP family, TCDB: 2.A.55), which catalyze the cotransport of protons and divalent cations.

Function and Mechanism: MntH2 is only poorly characterized; members of the NRAMP family are responsible for the uptake of divalent transition metals such as iron and manganese into cells. NRAMP proteins have been identified due to their role in resistance to intracellular bacterial pathogens. With K_M values in the lower µM range for their main substrates they efficiently select against Ca²⁺ and Mg²⁺, which are several orders of magnitude more abundant. NRAMP family members usually act as H⁺ coupled symporters. One proposed mechanism involves individual translocation pathways for protons and metal ions.

Organism and Localization: MntH2 resides within the plasma membrane of Enterococcus faecalis. Eucaryotic homologues have been also found in endosomes and lysosomes.

Substrates and Inhibitors: NRAMP transporters transport a wide range of divalent metal cations. MntH2 transports divalent transition metals such as Mn(II), Co(II), Zn(II) and Cd(II) and does not transport the earth metals Cu(II), Fe(II) and Ni(II). However, these earth metals are able to inhibit Mn(II) transport.

Related Transporters: Members of the NRAMP family are found across all kingdoms. Humans and rodents possess two distinct NRAMPs: the broad specificity NRAMP2 (SLC11a2) transports Fe²⁺ and H⁺ in a 1:1 stoichiometry with apparent affinities of 6 µM and 1 µM, respectively. It transports in order of substrate preference: Fe²⁺> Zn²⁺> Mn²⁺> Co²⁺> Ca²⁺> Cu²⁺> Ni²⁺> Pb²⁺. NRAMP1 (SLC11a1) has preference for Mn²⁺ over Fe²⁺ and has been reported to function by metal:H⁺ antiport. Mutations in NRAMP1 have been associated with susceptibility to infectious diseases such as tuberculosis and leprosy, and inflammatory diseases such as rheumatoid arthritis and Crohn's disease.