TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumExample
2.A.4.1.1









Cd2+, Zn2+, Co2+ efflux permease (also binds Cu2+ and Ni2+) (Anton et al., 2004)
Bacteria
Proteobacteria
CzcD of Ralstonia metallidurans (previously Alcaligenes eutrophus)
2.A.4.1.2









Zn2+, Co2+ efflux permease
Bacteria
Firmicutes
ZntA of Staphylococcus aureus
2.A.4.1.3









Cd2+ or Zn2+:H+ + K+ antiporter, CzcD
Bacteria
Firmicutes
CzcD of Bacillus subtilis
2.A.4.1.4









Zn2+ (Km=105 μM), Cd2+ (Km=90 μM):proton (Km=20 nM) antiport metal ion efflux permease, ZitB (Chao and Fu, 2004a); Zn2+ (Km=1.4 μM; Anton et al., 2004). It also takes up Ni2+ and Cu2+ (Rahman et al., 2008).
Bacteria
Proteobacteria
ZitB of E. coli (P75757)
2.A.4.1.5









The major Zn2+ resistance determinant, ZitA (Grover and Sharma, 2006Grover and Sharma, 2006)

Bacteria
Actinobacteria
ZitA of Mycobacterium smegmatis (A0QQH3)
2.A.4.1.6









Mitochondrial metal transporter 2
Eukaryota
Fungi
MMT2 of Saccharomyces cerevisiae
2.A.4.1.7









Dimeric Zn2+ efflux carrier of 299 aas and 5 TMSs, CzcD (Martin and Giedroc 2016).

Bacteria
Firmicutes
CzcD of Streptococcus pneumoniae
2.A.4.2.1









Mitochondrial Co2+/Zn2+ uptake (into mitochondria) permease.  A single mutation (N45I) increases the specificity for Fe2+ and decreases it for Co2+ (Lin et al., 2008).
Eukaryota
Fungi
Cotl of Saccharomyces cerevisiae
2.A.4.2.2









Vacuolar Zn2+, Cd2+ uptake (into vacuoles) permease (Zn2+/Cd2+:H+ antiporter). A single mutation (N44I) changes the specificity from Zn2+ to Fe2+ (Lin et al., 2008). Lin et al. (2009) have identified transmembrane residues that determine metal specificity.
Eukaryota
Fungi
Zrclp (ZnrP) of Saccharomyces cerevisiae
2.A.4.2.3









Plasma membrane Zn2+ efflux permease.  Substituing H43 with N (asn) changed the specificity from Zn2+ to Mn2+, and this difference was found in the Mn2+-specific metal ion exporter, ZnT10 (TC# 2.A.4.2.5) (Nishito et al. 2016).

Eukaryota
Metazoa
ZnT1 of Rattus norvegicus
2.A.4.2.4









Zn2+ exporter, CDF-1
Eukaryota
Metazoa
CDF-1 of Caenorhabditis elegans (Q95QW4)
2.A.4.2.5









Solute carrier family 30, member 10, ZnT10.  Manganese efflux transporteer of 485 aas and 6 TMSs in a 4 + 2 TMS arrangement with two long hydrophilic regions between residues 135 and 240, and residues 300 and 485 (Nishito et al. 2016).  Homozygous mutations lead to the development of familial manganese Mn2+-induced parkinsonism; it is a cell surface-localized Mn2+ efflux transporter, and parkinsonism-causing mutations block its trafficking and efflux activity. Residues in the transmembrane and C-terminal domains together confer optimal Mn2+ transport capability (Zogzas et al. 2016).

Eukaryota
Metazoa
SLC30A10 or ZnT10 of Homo sapiens
2.A.4.2.6









Zinc transporter 1 (ZnT-1) (Solute carrier family 30 member 1)
Eukaryota
Metazoa
SLC30A1 of Homo sapiens
2.A.4.2.7









ZnT63C Zinc exporter, ZnT1, of 545 aas and 5 putative TMSs (Lye et al. 2013; Dechen et al. 2015).

Eukaryota
Metazoa
ZnT63C of Drosophila melanogaster
2.A.4.2.8









Vacuolar CDF1 transporter.  Transports Zn2+, Co2+ and Cd2+ but not Mn2+, of 487 aas and 6 TMSs (Sácký et al. 2016).

Eukaryota
Fungi
CDF1 of Russula atropurpurea
2.A.4.3.1









Vesicular Zn2+ uptake (into endosomal/lysosomal vesicles) permease, ZnT2. There are two isoforms due to alternative splicing, 35 kDa (plasma membrane localized) and 42 kDa (endosome/secretory compartment localized) (Lopez and Kelleher, 2009).

Eukaryota
Metazoa
ZnT2 of Rattus norvegicus
2.A.4.3.2









Vesicular Zn2+ uptake (into synaptic vesicles) permease, ZnT3 (SLC30A subfamily). ZnT-3 regulates presynaptic Erk1/2 signaling and hippocampus-dependent memory (Sindreu et al., 2011).

Eukaryota
Metazoa
SLC30A3 of Homo sapiens
2.A.4.3.3









Mammary epithelia/brain Zn2+ transporter ZnT4 (the cause of inherited zinc deficiency in the lethal milk (lm) syndrome of mice, due to a nonsense mutation at codon 297 (arg) in the ZnT4 gene) (Huang and Gitschier, 1997).
Eukaryota
Metazoa
ZnT4 of Mus musculus
(O35149)
2.A.4.3.4









Plant root and leaf vacuolar Zn2+ transporter, ZAT-1 or MTP1 (metal tolerance protein 1) (Desbrosses-Fonrouge et al., 2005). Loss of the cytoplasmic histidine-rich loop, where 4 Zn2+ (or Ni2+ or Co2+) bind, stimulates transport activity (Kawachi et al., 2008), presumably providing a feedback sensor of cytoplasmic Zn2+ (Tanaka et al. 2013). The barley orthologue has broader metal specificity (Podar et al., 2012). Critical residues for function, ion selectivity and structure have been identified (Kawachi et al., 2012).

Eukaryota
Viridiplantae
MTP1 of Arabidopsis thaliana
(Q9ZT63)
2.A.4.3.5









Homodimeric solute carrier family 30 (zinc transporter), member 8, ZnT8.  An inherited R325W mutant gives aberant zinc transport in pancreatic beta cells (Weijers 2010). It is chiefly expressed in pancreatic islet cells, where it mediates zinc (Zn2+) uptake into secretory granules. It plays a role in gllucose tolerance (Mitchell et al. 2016).

Eukaryota
Metazoa
SLC30A8 of Homo sapiens
2.A.4.3.6









solute carrier family 30 (zinc transporter), member 2
Eukaryota
Metazoa
SLC30A2 of Homo sapiens
2.A.4.3.7









Zinc transporter 4 (ZnT-4) (Solute carrier family 30 member 4)
Eukaryota
Metazoa
SLC30A4 of Homo sapiens
2.A.4.3.8









Metal tolerance protein 4, MTP4, of 386 aas.  Exports Zn2+ and Cd2+ (Migocka et al. 2015).  MTP1 transports the same two ions but is less restrictive with respect to the tissues in which the protein is synthesized.

Eukaryota
Viridiplantae
MTP4 of Cucumis sativus (Cucumber)
2.A.4.3.9









Co2+ resistance protein, DmeF, of 382 aas and 6 TMSs. Co2+ export appears to be its dominant physiological function, but it may also export other heavy metal ions such as Zn2+ and Cd2+ (Munkelt et al. 2004).

Bacteria
Proteobacteria
DmeF of Cupriavidus metallidurans (Ralstonia metallidurans)
2.A.4.4.1









Heteromeric nuclear/ER Zn2+ uptake permease, Msc2/Zrg17 (Ellis et al., 2005).  Zrg17 is also called Meiotic sister-chromatid recombination-related protein or metal cation transporter Msc2p of 724 aas and 15 TMSs in a 7 + 2 + 6 TMS arrangement.  Only the last 6 TMSs are homologous to CDF transporters.

Eukaryota
Fungi
Msc2/Zrg17 heteromeric Zn2+ transporter of Saccharomyces cerevisiae
Msc2 (Q03455)
Zrg17 (P53735)
2.A.4.4.2









Zn2 Transporter, LbrM31

Eukaryota
Kinetoplastida
LbrM31 of Leishmania braziliensis (A4HJM3)
2.A.4.4.3









Golgi/secretory granule Zn2 uptake (into Golgi or granules) permease, ZnT5 or ZTL1 (ZnT5 forms heterooligomers with ZnT6) (Ellis et al., 2005; Ishihara et al., 2006; Fukunaka et al. 2009) (Variant B catalyzes bidirectional transport (Valentine et al., 2007) )

Eukaryota
Metazoa
SLC30A5 or ZnT5 of Homo sapiens
2.A.4.4.4









Golgi/secretory granule/endoplasmic reticulum Zn2+ uptake (into Golgi, the ER, or granules) permease, ZnT6.  ZnT6 forms heterooligomers with ZnT5 (Ellis et al., 2005; Ishihara et al., 2006; Fukunaka et al. 2009).

Eukaryota
Metazoa
SLC30A6 of Homo sapiens
2.A.4.4.5









Golgi/secretory granule Zn2+ uptake (into Golgi or granules) permease, ZnT7 (Ishihara et al., 2006)
Eukaryota
Metazoa
SLC30A7 of Homo sapiens
2.A.4.4.6









Metal tolerance protein C2 (AtMTPc2) (AtMTP5).  Forms a large, active, heteromeric complex with MTP12 in the golgi and pumps Zn2+ into this organelle (Fujiwara et al. 2015).  MTP12 has 798 aas and 14 TMSs.  Its UniProt acc # is A0A0A8IL98.

Eukaryota
Viridiplantae
MTPC2 or MTP5 of Arabidopsis thaliana
2.A.4.4.7









Lead (Pb2+) efflux transporter of 211 aas, PbtF (HloĹžková et al. 2013).

Bacteria
Proteobacteria
PbtF of Achromobacter xylosoxidans
2.A.4.4.8









Uncharacterized protein of 701 aas and 16 TMSs, where the last 6 TMSs are homologous to CDF transporters.

Eukaryota
Fungi
UP of Eremothecium cymbalariae (Yeast)
2.A.4.5.1









Golgi/endomembrane Mn2+-specific CDF transporter (394 aas) (Peiter et al., 2007).  A rice homologue, MTP8.1, has been characterized (Chen et al. 2016).

Eukaryota
Viridiplantae
MTP11.1 of Populus trichocarpa (A4ZUV2)
2.A.4.5.2









CDF2 transporter for Zn2+ and Co2+ but not Cd2+ or Mn2+ of 417 aas and 5 TMSs (Sácký et al. 2016).

Eukaryota
Fungi
CDF2 of Russula atropurpurea
2.A.4.5.3









MTP8.1 is a tonoplast-localized manganese transporter of 400 aas and 6 TMSs. Critical residues for function in the rice orthologue have been identified (Chen et al. 2016).

Eukaryota
Viridiplantae
MTP8.1 of Hordeum vulgare (Barley)
2.A.4.6.1









CDF transporter, ZnT9 of unknown specificity (568 aas) (Montanini et al., 2007)
Eukaryota
Metazoa
SLC30A9 of Homo sapiens
2.A.4.7.1









Zn2+/Cd2+/Hg2+/Fe2+:H+ antiporter, YiiP or FieF (Chao and Fu, 2004b; Grass et al., 2005; Wei et al., 2004; Wei and Fu, 2006). The structure (3.8 Å resolution) reveals a homodimer interconnected at the cytoplasmic domain through four Zn2+ ions. A 6 TMS bundle features of a tetrahedral Zn2+ binding site (Lu and Fu, 2007). The gated water access to the transport site enables a stationary proton gradient to facilitate the conversion of zinc-binding energy to the kinetic power stroke of a vectorial zinc transport (Gupta et al. 2014).

Bacteria
Proteobacteria
YiiP of E. coli (P69380)
2.A.4.7.2









Metal tolerance protein C1 (AtMTPc1) (AtMTP6)
Eukaryota
Viridiplantae
MTPC1 of Arabidopsis thaliana
2.A.4.7.3









Putative magnetosome membrane iron transporter, MamB.  Forms a heterodimeric stable complex with MamM which stabilizes MamB.  MamB also interacts with other proteins including the PDZ1 domain of MamE (Q6NE61).  Both MamB and MamM are essential for magnetite biomineralization and are involved in several steps in magnetosome formation, but only MamB is essential for formation of magnetosome membrane vesicles (Uebe et al. 2011).  Implicated in iron uptake due to homology with other CDF transporters.

Bacteria
Proteobacteria
MamB of Magnetospirillum gryphiswaldense
2.A.4.7.4









Putative magnetosome membrane iron transporter, MamM.  Forms a heterodimeric stable complex with MamB which it stabilizes.  MamB; see 2.A.4.7.3) also interacts with other proteins including the PDZ1 domain of MamE (Q6NE61).  Both MamB and MamM are essential for magnetite biomineralization and are involved in several steps in magnetosome formation, but only MamB is essential for formation of magnetosome membrane vesicles (Uebe et al. 2011).  Implicated in iron uptake due to homology with other CDF transporters.

Bacteria
Proteobacteria
MamM of Magnetospirillum gryphiswaldense
2.A.4.7.5









Cd2+/Zn2+ efflux pump, YiiP or FieF. A low resolution structure in the open configuration has been determined by cryoelectron microscopy (Coudray et al. 2013).

Bacteria
Proteobacteria
YiiP of Shewanella oneidensis (Q8E919)
2.A.4.7.6









Bacteria
Firmicutes
MntE of Streptococcus pneumoniae
2.A.4.7.7









Mn2+ efflux pump, YiiP, probably a Mn2+:H+ antiporter.  Necessary for efficient nodulation of alfalfa plants (Raimunda and Elso-Berberián 2014)

Bacteria
Proteobacteria
YiiP of Sinorhizobium meliloti  
2.A.4.7.8









CDF protein, exporting Zn2+ and Cd2+ (323 aas). It lacks the C-terminal hydrophilic domain (CTD) common to many CDF homologues (Kolaj-Robin et al. 2015).

Bacteria
Proteobacteria
CDF homologue of Maricaulis maris
2.A.4.7.9









Ferrous iron detoxifying protein, FieF, of 337 aas and 6 TMSs.  Also probably exports Zn2+, Co2+, Cd2+ and Ni2+ (Munkelt et al. 2004).

Bacteria
Proteobacteria
FieF of Cupriavidus metallidurans (Ralstonia metallidurans)
2.A.4.7.10









Cobalt/zinc resistance protein B, CzrB, of 291 aas and 6 TMSs.  It has a cytosolic extramembranal C-terminus. This 92-residue fragment may function independently of the full-length integral membrane protein. X-ray analyses of this fragment to 2.2 A resolution with and 1.7 A without zinc ions have been solved. The former has at least two zinc ions bound per monomer (Höfer et al. 2007).  Full-length variants of CzrB in the apo and zinc-loaded states were generated by homology modeling with the Zn2+/H+ antiporter YiiP. The model suggests a way in which zinc binding to the cytoplasmic fragment creates a docking site to which a metallochaperone can bind for delivery and transport of zinc. A proposal was advanced that it functions as a metallochaperone and regulates the zinc-transporting activity of the full-length protein. The latter requires that zinc binding becomes uncoupled from the creation of a metallochaperone-docking site on CzrB (Cherezov et al. 2008).

Bacteria
Deinococcus-Thermus
CzrB of Thermus thermophilus
2.A.4.8.1









CDF Family homologue with MMT1 domain

Bacteria
Actinobacteria
CDF porter of Streptomyces coelicolor
2.A.4.8.2









CDF Family member

Bacteria
Actinobacteria
CDF cation efflux carrier of Mycobacterium tuberculosis
2.A.4.8.3









Zn2+ transporter, TMEM163, of 289 aas and 6 TMSs.  Interacts with TrpML1 (TC# 1.A.5.3.1) to influence Zn2+ homeostasis, possibly by pumping out Zn2+.  May be involved in the human lipid storage disorder, mucolipidosis type IV (MLIV), caused by Zn2+ overload (Cuajungco et al. 2014). TMEM163 is found in synaptic vesicles where it is called SV31 (Burré et al. 2007). It plays a role in Zn2+ uptake into lysosomes (Cuajungco and Kiselyov 2017).

Eukaryota
Metazoa
TMEM163 of Homo sapiens