TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameOrganismal TypeExample
2.A.55.1.1









High-affinity Me2+ (Fe2+, Mn2+, Zn2+, Cu2+, Cd2+, Ni2+, Co2+) uptake transporter, Smf1p.  Important for oxidative stress protection.

Eukaryotes, bacteria, archaea

Smf1p of Saccharomyces cerevisiae
2.A.55.1.2









Low-affinity Me2+ (Mn2+, Cu2+) uptake transporter, Smf2p.  Essential for manganese uptake.

Eukaryotes, bacteria, archaea

Smf2p of Saccharomyces cerevisiae
2.A.55.1.3









Intracellular (Golgi?) heavy metal transporter, Smf3p
Yeast
Smf3p of Saccharomyces cerevisiae (NP_013134)
2.A.55.1.4









Manganese transporter Pdt1

Yeast
Pdt1 of Schizosaccharomyces pombe
2.A.55.2.1









Heavy metal (Fe2+, Zn2+, Mn2+, Cu2+, Cd2+, Co2+, Ni2+ and Pb2+) ion:H+ symporter, Nramp2 or divalent metal transporter, DMT1. A 12 TMS topology with intracellular N- and C- termini is established. Two-fold structural symmetry in the arrangement of membrane helices for TM1-5 and TM6-10 (conserved Slc11 hydrophobic core) is suggested (Czachorowski et al., 2009).  A conserved motif in a central flexible region of TMS1 (DPGN) binds the metal ion (Wang et al. 2011).  Upregulated by iron deficiency and downregulated by iron loading (Nam et al. 2013).  NRAMP2 also serves as the Sindbis alpha virus receptor (Rose et al. 2011).

Animals

DMT1 (SLC11A2) of Homo sapiens
2.A.55.2.2









Me2+ (Fe2+, Cd2+, Co2+):H+ symporter, DCT1 (Nramp2) (Splice variant isoforms serve different functions). The stoichiometry between metal ion and proton in the symport process catalyzed by DCT1 varies under different conditions due to mechanistic proton slip. A single reciprocal mutation, I144F, in TMS2 of DCT1 abolished the metal ion transport activity, increased the slip currents, and generated sodium slip currents (Nevo, 2007). A double mutation, adding F227I in TMS4 to I144F restored the uptake activity of DCT1 and reduced the slip currents. Thus, these regions are important in coupling metal ion and proton symport (Nevo, 2007).  NRAMP2 also serves as the Sindbis alpha virus receptor (Rose et al. 2011).  Three isoforms are expressed differentially in different cell types and are developmentally regulated (Ding et al. 2013).

Animals

DCT1 of Rattus norvegicus
2.A.55.2.3









Macrophage divalent cation (Mn2+ > Fe2+):H+ antiporter (catalyzes divalent cation efflux and regulates cation homeostasis), NRAMP1 or Slc11a2. (Techau et al., 2007). The G212V mutation leads to microcytic anemia and liver iron overload (Bardou-Jacquet et al., 2011). Multiple targeting motifs direct NRAMP1 into lysosomes (Cheng and Wang, 2012). The structure and topology has been studied revealing a symmetric but inversely oriented arrangement (Li et al., 2012).

Animals
SLC11A1 of Homo sapiens
2.A.55.2.4









The major root plasma membrane high affinity Me2+(Fe2+ Co2+ Mn2+) uptake transporter, NRAMP-1 (stimulated by Mn2+ deficiency) (Cailliatte et al., 2010)

Plants

NRAMP-1 of Arabidopsis thaliana (Q9SAH8)
2.A.55.2.5









Nramp aluminum transporter 1, Nrat1; specific for trivalent Al ion in rice (Xia et al., 2010; Xia et al. 2011).

Plants

Nrat1 of Oryza sativa (Q6ZG85)
2.A.55.2.6









Mn2+ transporter, MntH (Hohle and O'Brian, 2009)

Bacteria 

MntH of Bradyrhizobium japonicum (Q89K67) 
2.A.55.2.7









Iron transporter, NRAMP isoform III (Lin et al., 2011).

Protozoa (Alveolata)

NRAMP isoform III of Perkinsus marinus (D5FGJ2)
2.A.55.2.8









Ethylene-insensitive protein 2 (AtEIN2) (EIN-2) (Cytokinin-resistant protein AtCKR1)
Plants
EIN2 of Arabidopsis thaliana
2.A.55.2.9









NRAMP1 (SLC11a1) of 533 aas and 11 TMSs.  Regulates iron homeostasis and bacterial infection; present in phagosomes and macroinosomes (Peracino et al. 2013).

Slime molds

NRAMP1 of Dictyostelium discoideum
2.A.55.2.10









NRAMP2 (SLC11a2) of 552 aas and 10 TMSs.  Inovoled in iron hoemeostasis and infectivity together with NRAMP1 (TC#2.A.55.2.9).  Present in the contractile vacuole which regulates osmolarity and possible stores iron (Peracino et al. 2013).

Slime molds

NRAMP2 of Dictyostelium discoideum
2.A.55.2.11









NRAMP2 of 596 aas and 12 TMSs.  NRAMP2 also serves as the Sindbis alpha virus receptor (Rose et al. 2011).

Insects

NRAMP2 of Drosophila melanogaster
2.A.55.2.12









VO2+ (vanidate) NRAMP uptake system in vacuoles of vanadocytes (587 aas; Ueki et al. 2011).

Ascidians

Vanidate transporter of Ascidia sydneiensis samea (Vanadium-rich ascidian)

 
2.A.55.2.13










Enterocyte iron uptake system, NRAMP or DMT1 of 558 aas and 13 TMSs.  Inhibited by lead and cadmium ions competitively (Kwong et al. 2010).

Animals

DMT1 of Oncorhynchus mykiss (Rainbow trout) (Salmo gairdneri)
2.A.55.2.14









NRAMP3 iron/cadmium transporter of 512 aas (Wei et al. 2009).

Plants

NRAMP3 of Noccaea caerulescens
2.A.55.2.15









Divalent and aluminum transporter, Smf3.  Mediates aluminum-induced dopamine neuron degeneration (VanDuyn et al. 2013).

Animals

Smf3 of Caenorhabditis elegans
2.A.55.2.16









Fe2+/Mn2+ transporter, Smf1

Animals

Smf1 of Caenorhabditis elegans
2.A.55.3.1









Me2+ (Mn2+, Fe2+, Cd2+, Co2+, Zn2+, Ni2+):H+ symporter, MntH (Mn2+ · MntR and Fe2+ · Fur repressible). Specific resides in TMS1 and 6 line the pore and play a role in pH regulation (Courville et al., 2004; Haemig et al. 2010). Important for virulence in Salmonella (Haemig et al. 2010). Important for virulence in Salmonella (Karlinsey et al., 2010).

Bacteria

MntH (YfeP) of E. coli (P0A769)
2.A.55.3.2









MntH homologue (20% I) of unknown function
Bacteria
YcsG of Bacillus subtilis (P42964)
2.A.55.3.3









Manganese transport protein MntH
Bacilli
MntH of Bacillus subtilis
2.A.55.3.4









Actinobacteria

2.A.55.3.5









Uncharqacterized permease of 406 aas

Proteobacteria

UP of Pseudomonas stutzeri