TCDB » SEARCH

TCID	Name	Domain	Kingdom/Phylum	Protein(s)
2.A.4.1.1	Cd²⁺, Zn²⁺, Co²⁺ efflux permease (also binds Cu²⁺ and Ni²⁺) (Anton et al., 2004)	Bacteria	Pseudomonadota	CzcD of Ralstonia metallidurans (previously Alcaligenes eutrophus)
2.A.4.1.2	Zn²⁺, Co²⁺ efflux permease	Bacteria	Bacillota	ZntA of Staphylococcus aureus
2.A.4.1.3	Cd²⁺ or Zn²⁺:H⁺ + K⁺ antiporter, CzcD	Bacteria	Bacillota	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	Pseudomonadota	ZitB of E. coli (P75757)
2.A.4.1.5	The major Zn²⁺ resistance determinant, ZitA (Grover and Sharma, 2006 Grover and Sharma, 2006)	Bacteria	Actinomycetota	ZitA of Mycobacterium smegmatis (A0QQH3)
2.A.4.1.6	Mitochondrial metal transporter 2	Eukaryota	Fungi, Ascomycota	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	Bacillota	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, Ascomycota	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, Ascomycota	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). Expression on the cell surface is controlled by cellular zinc levels (Nishito and Kambe 2019).	Eukaryota	Metazoa, Chordata	ZnT1 of Rattus norvegicus
2.A.4.2.4	Zn²⁺ exporter, CDF-1	Eukaryota	Metazoa, Nematoda	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). Residues involved in Mn²⁺ binding in the transmembrane domain have been identified, and they differ in position and nature from the Zn²⁺ binding site in Zn²⁺ transporting members of the CDF family (Zogzas and Mukhopadhyay 2018). Loss of ZnT10 expression caused by autosomal mutations in the ZnT10 gene leads to hypermanganesemia in multiple organs (Levy et al. 2019). The cellular transport of Mn²⁺ is coupled to a reciprocal movement of Ca²⁺. Replacing a single asparagine residue in ZnT10 (Asn-43) with threonine (ZnT10 N43T) converted the Mn²⁺/Ca²⁺ exchanger into an uncoupled channel permeable to both Ca²⁺ and Mn²⁺(Levy et al. 2019). It is expressed in the CNS (Sreedharan et al. 2011).	Eukaryota	Metazoa, Chordata	SLC30A10 or ZnT10 of Homo sapiens
2.A.4.2.6	Zinc transporter 1 (ZnT-1 or ZnT1) (Solute carrier family 30 member 1). The loss of the sialic acid transporter SLC35A1/CST (TC# 2.A.7.12.11) and the zinc transporter, ZnT1, affected cell survival upon infection with cytolytic vesicular stomatitis virus (VSV). Both of these transporters seem to play a role in the apoptotic response induced by VSV (Moskovskich et al. 2019). ZnT1 functions by Zn²⁺:H⁺ antiport and has a C-terminal hydrophilic domain that is a dimer in solution with a V-shaped core (Cotrim et al. 2021). There are 10 ZnT proteins in humans, but only ZnT1 is a zinc exporter in the plasma membrane, and only ZnT10 is a Mn²⁺ exporter; a reliable in vitro assay has been developed for measuring Zn²⁺ uptake (Ben Yosef et al. 2023). Somatic SLC30A1 mutations altering zinc transporter ZnT1 cause aldosterone-producing adenomas and primary aldosteronism (Rege et al. 2023).	Eukaryota	Metazoa, Chordata	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, Arthropoda	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, Basidiomycota	CDF1 of Russula atropurpurea
2.A.4.2.9	The plasma membrane zinc efflux system, ZnT-1, of 485 aas and 6 predicted TMSs with a large histidine-rich intracellular loop between TMSs 4 and 5 and intracellular C- and N-termini (Balesaria and Hogstrand 2006).	Eukaryota	Metazoa, Chordata	ZnT-1 of Takifugu rubripes (Japanese pufferfish) (Fugu rubripes)
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, Chordata	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, Chordata	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, Chordata	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). In Citrus sinensis, expression is induced by Cd²⁺ (Fu et al. 2017).	Eukaryota	Viridiplantae, Streptophyta	MTP1 of Arabidopsis thaliana (Q9ZT63)
2.A.4.3.5	Homodimeric solute carrier family 30 (zinc transporter), member 8, ZnT8 or ZnT-8. 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 glucose tolerance (Mitchell et al. 2016). ZnT8 is one of four human vesicular zinc transporters. It supplies millimolar zinc concentrations to insulin granules in pancreatic beta-cells, affecting insulin processing, crystallisation, and secretion. ZnT8 has a transmembrane and a C-terminal cytosolic domain; the latter has important functions and purportedly mediates protein-protein interactions, senses cytosolic zinc, and channels zinc to the transport site in the transmembrane domain (Parsons et al. 2018). The variant, W325R, in the C-terminal domain (CTD) increases the risk to develop type 2 diabetes and affects autoantibody specificity in type 1 diabetes. The CTDs of the WT and mutant proteins form tetramers which are stabilized by zinc binding and exhibit negligible differences in their secondary structural content and zinc-binding affinities in solution (Ullah et al. 2020). Xue et al. 2020 described cryo-EM structures in both outward- and inward-facing conformations. HsZnT8 forms a dimeric structure with four Zn²⁺ binding sites within each subunit with a highly conserved primary site in the TMD housing the Zn²⁺ substrate. An interfacial site between the TMD and the CTD modulates the Zn²⁺ transport activity. Two adjacent sites buried in the cytosolic domain are chelated by conserved residues from CTD and the His-Cys-His (HCH) motif from the N-terminal segment of the neighboring subunit. A comparison of the outward- and inward-facing structures reveals that the TMD of each subunit undergoes a large structural rearrangement, allowing for alternating access to the primary Zn²⁺ site during the transport cycle (Xue et al. 2020). The C-terminal domain of the human zinc transporter hZnT8 Is structurally indistinguishable from its disease risk variant (R325W) (Ullah et al. 2020). The dynamics of ZnT8 have been studied (Sala et al. 2021), revealing that packing of the TMSs affects channel accessibility from the cytosol. The dimer interface that keeps the two TM channels in contact became looser in both variants upon zinc binding to the transport site, suggesting that this may be an important step toward the switch from the inward- to the outward-facing states of the protein (Sala et al. 2021). The C-terminal cysteines, which are part of the cytosolic domain, are involved in a metal chelation and/or acquisition mechanism, and provides the first example of metal-thiolate coordination chemistry in zinc transporters (Catapano et al. 2021). Human ZnT8 (SLC30A8) is a diabetes risk factor and a zinc transporter (Daniels et al. 2020). ZnT8 loss of function mutations increase resistance of human embryonic stem cell-derived beta cells to apoptosis unswe low zinc conditions (Sui et al. 2023). Protons may disrupt Zn²⁺ coordination at the transmembrane Zn²⁺-binding site in the lumen-facing state, thus facilitating Zn²⁺ release from ZnT8 into the lumen (based on the cryoEM structure of the Xenopus tropecalis ZnT8 (Zhang et al. 2023). .	Eukaryota	Metazoa, Chordata	SLC30A8 of Homo sapiens
2.A.4.3.6	solute carrier family 30 (zinc transporter), member 2	Eukaryota	Metazoa, Chordata	SLC30A2 of Homo sapiens
2.A.4.3.7	Zinc transporter 4 (ZnT-4) (Solute carrier family 30 member 4)	Eukaryota	Metazoa, Chordata	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, Streptophyta	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	Pseudomonadota	DmeF of Cupriavidus metallidurans (Ralstonia metallidurans)
2.A.4.3.10	CDF transporter, MTP1 of 640 aas and 6 TMSs. It transports zinc (Zn²⁺) and cobalt (Co²⁺) (Ibuot et al. 2020).	Eukaryota	Viridiplantae, Chlorophyta	MTP1 of Chlamydomonas reinhardtii
2.A.4.3.11	Zn²⁺Transporter, LbrM31, of 443 aas and 6 or 7 TMSs.	Eukaryota	Euglenozoa	LbrM31 of Leishmania braziliensis (A4HJM3)
2.A.4.3.12	Zinc transporter, Ttm-1, of 410 aas and 6 TMSs in a 2 + 2 + 2 TMS arrangement. It promotes excretion of zinc from intestinal cells into the intestinal lumen in response to increased dietary zinc (Roh et al. 2013). It is also involved in cadmium resistance, possibly by promoting its transport from cells (Huffman et al. 2004). It is also involved in resistance to B. thuringiensis pore-forming toxin Cry5B downstream of the sek-1 and pmk-1 MAPK kinase pathway.	Eukaryota	Metazoa, Nematoda	Ttm-1 of Caenorhabditis elegans
2.A.4.3.13	Zn²⁺, Fe²⁺ and Co²⁺ exporter, AitP, of 321 aas and 6 TMSs. The N₂-fixing bacteria, Sinorhizobium meliloti, is a suitable model to determine the roles of Co²⁺-transporting Co-eCDF in Fe²⁺ homeostasis because it has a putative member of this subfamily, AitP, and two specific Fe²⁺-export systems. An insertional mutant of AitP showed Co²⁺ sensitivity and accumulation, Fe accumulation and hydrogen peroxide sensitivity, but not Fe²⁺ sensitivity, despite AitP being a bona fide low affinity Fe²⁺ exporter as demonstrated by the kinetic analyses of Fe²⁺ uptake into everted membrane vesicles (Mihelj et al. 2023).	Eukaryota	Pseudomonadota
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, Ascomycota	Msc2/Zrg17 heteromeric Zn²⁺ transporter of Saccharomyces cerevisiae Msc2 (Q03455) Zrg17 (P53735)
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, Chordata	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, Chordata	SLC30A6 of Homo sapiens
2.A.4.4.5	Golgi/secretory granule Zn²⁺ uptake (into Golgi or granules) permease, ZnT7 (Ishihara et al., 2006). Bui et al. 2023 presented the 2.2-3.1 Å-resolution cryo-EM structures of the human Zn²⁺/H⁺antiporter ZnT7 in Zn²⁺-bound and unbound forms. Cryo-EM analyses show that hZnT7 exists as a dimer via tight interactions in both the cytosolic and transmembrane (TM) domains of two protomers, each of which contains a single Zn²⁺-binding site in its TM domain. hZnT7 undergoes a TM-helix rearrangement to create a negatively charged cytosolic cavity for Zn²⁺ entry in the inward-facing conformation and widens the luminal cavity for Zn²⁺ release in the outward-facing conformation. An exceptionally long cytosolic histidine-rich loop, characteristic of hZnT7, binds two Zn²⁺ ions, seemingly facilitating Zn²⁺ recruitment to the TM metal transport pathway. These structures allow mechanisms of hZnT7-mediated Zn²⁺ uptake into the Golgi to be proposed (Bui et al. 2023).	Eukaryota	Metazoa, Chordata	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. In Citrus sinensis, expression is induced by Zn²⁺ in roots (Fu et al. 2017).	Eukaryota	Viridiplantae, Streptophyta	MTPC2 or MTP5 of Arabidopsis thaliana
2.A.4.4.7	Lead (Pb²⁺) efflux transporter of 211 aas, PbtF (Hložková et al. 2013).	Bacteria	Pseudomonadota	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, Ascomycota	UP of Eremothecium cymbalariae (Yeast)
2.A.4.4.9	Metal tolerance protein 12, MTP12 of 300 aas and 6 TMSs. In Citrus sinensis, expression is induced by Cd²⁺ in roots (Fu et al. 2017).	Eukaryota	Viridiplantae, Streptophyta	MTP12 of Arabidopsis thaliana
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, Streptophyta	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, Basidiomycota	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, Streptophyta	MTP8.1 of Hordeum vulgare (Barley)
2.A.4.5.4	Metal tolerance protein 8, MTP8, of 411 aas and 6 TMSs. In Citrus sinensis, expression is induced by Mn²⁺ in roots (Fu et al. 2017). In A. thaliana, MPT8 determines the localization of manganese and iron in seeds (Chu et al. 2017). The endodermal vacuole is the iron and manganese storage compartment in the A. thaliana embryo (Roschzttardtz et al. 2009).	Eukaryota	Viridiplantae, Streptophyta	MTP8 in Arabidopsis thaliana
2.A.4.5.5	Metal tolerance protein 11, MTP11, of 298 aas and 5 TMSs. In Citrus sinensis, expression is induced by Zn²⁺ in leaves (Fu et al. 2017).	Eukaryota	Viridiplantae, Streptophyta	MTP11 of Arabidopsis thaliana
2.A.4.5.6	CDF transporter, MTP3, of 458 aas and 7 TMSs. It transports Mn²⁺, Zn²⁺ and Co²⁺ (Ibuot et al. 2020).	Eukaryota	Viridiplantae, Chlorophyta	MTP3 of Chlamydomonas reinhardtii (Chlamydomonas smithii)
2.A.4.5.7	Mn²⁺ transporting CDF porter, MTP4, of 538 aas and 6 TMSs.	Eukaryota	Viridiplantae, Chlorophyta	MTP4 of Chlamydomonas reinhardtii (Chlamydomonas smithii)
2.A.4.5.8	Metal tolerance protein 4 (MTP4) of 412 aas and 6 central TMSs It has dual functions in maintaining zinc homeostasis in tea plants (Li et al. 2024).	Eukaryota	Viridiplantae, Streptophyta	MTP4 of Citrus unshi
2.A.4.6.1	CDF transporter, ZnT9 (568 aas) (Montanini et al., 2007). Mutations cause autosomal recessive cerebro-renal syndrome and affect intracellular Zinc homeostasis (Perez et al. 2017). Birk-Landau-Perez syndrome is a genetic disorder caused by biallelic pathogenic variants in SLC30A9, causing a complex movement disorder, developmental regression, oculomotor abnormalities, and renal impairment (Steel et al. 2023).	Eukaryota	Metazoa, Chordata	SLC30A9 of Homo sapiens
2.A.4.6.2	Metal tolerance protein C4, MTPC4 of 457 aas and 6 TMSs. It is involved in sequestration of excess metal ions, including Zn²⁺ in the cytoplasm into vacuoles to maintain metal homeostasis.	Eukaryota	Viridiplantae, Streptophyta	MTPC4 of Arabidopsis thaliana (Mouse-ear cress)
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). Of the two cavities of the dimer, only one was accessible from the cytosol during transport. Zinc(II) binding to D49 of the transport site triggered a rearrangement of the TMS that closed the accessible cavity. The free-energy profiles of metal transit in the channel suggested the existence of a high barrier preventing release from the transport site (Sala et al. 2019). The mechanism of zinc transport through YiiP has been proposed (Sharma and Merz 2022).	Bacteria	Pseudomonadota	YiiP of E. coli (P69380)
2.A.4.7.2	Metal tolerance protein C1 (AtMTPc1) (AtMTP6)	Eukaryota	Viridiplantae, Streptophyta	MTPC1 of Arabidopsis thaliana
2.A.4.7.3	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. MamM was used to probe the role of the hydrophilic C-terminal domain (CTD) in metal recognition and selectivity. Different metals bind to MamM CTD, suggesting a varying level of functional discrimination between CDF domains. Thus, CDF CTDs play a role in metal selectivity. MamM's CTD discriminates against Mn²⁺, supporting a role in preventing magnetite formation poisoning in magnetotactic bacteria via Mn²⁺ incorporation (Barber-Zucker et al. 2020).	Bacteria	Pseudomonadota	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 TC# 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). Most CDF proteins contain two domains, the cation transporting transmembrane domain and the regulatory cytoplasmic C-terminal domain (CTD). A MamM M250P mutation that is synonymous with the disease-related mutation L349P of the human CDF protein, ZnT-10 causes severe structural changes in its CTD, resulting in abnormally reduced function.Thus, the CTD fold is critical for the CDF proteins' proper function and suggest that the CDF cytoplasmic domain is a CDF regulatory element (Barber-Zucker et al. 2016). MamM's CTD can discriminate against Mn²⁺, supporting its postulated role in preventing magnetite formation poisoning in magnetotactic bacteria via Mn²⁺ incorporation (Barber-Zucker et al. 2020).	Bacteria	Pseudomonadota	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	Pseudomonadota	YiiP of Shewanella oneidensis (Q8E919)
2.A.4.7.6	Dimeric Mn²⁺ efflux transporter, MntE of 394 aas (Rosch et al. 2009; Lisher et al. 2013 ; Jakubovics and Valentine 2009; Martin and Giedroc 2016).	Bacteria	Bacillota	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	Pseudomonadota	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	Pseudomonadota	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	Pseudomonadota	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	Deinococcota	CzrB of Thermus thermophilus
2.A.4.7.11	Magnetosome protein, MamV, of 322 aas and 5 TMSs. Putative Co/Zn/Cd cation transporter (Smalley et al. 2015).	Bacteria	Proteobacteria	MamV of Magnetospirillum magnetotacticum MS-1
2.A.4.8.1	CDF Family homologue with MMT1 domain	Bacteria	Actinomycetota	CDF porter of Streptomyces coelicolor
2.A.4.8.2	CDF Family member	Bacteria	Actinomycetota	CDF cation efflux carrier of Mycobacterium tuberculosis
2.A.4.8.3	Zn²⁺ transporter, TMEM163 or Znt11, of 289 aas and 6 TMSs. It interacts with TrpML1 (TC# 1.A.5.3.1), but by itself, it can pump out Zn²⁺ (Sanchez et al. 2019). It 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). TMEM163 proteins catalyze Zn²⁺ efflux from cells and are critical for the biogenesis of platelet dense granules in mice (Yuan et al. 2021). TMEM163's discovery, transport feature, protein interactome, and similarities, as well as differences, with known SLC30 (ZnT) protein family members have been reviewed (Styrpejko and Cuajungco 2021). These authors also examined recent reports that implicate TMEM163 directly or indirectly in various human diseases such as Parkinson's disease, Mucolipidosis type IV and diabetes. TMEM163 is a dimer that catalyzes Zn²⁺efflux from cells, or uptake into intracellular vesicles including lysosomes. TMEM163 dimerizes with itself, but it also heterodimerizes with ZNT1, ZNT2, ZNT3, and ZNT4 proteins (Escobar et al. 2022).	Eukaryota	Metazoa, Chordata	TMEM163 of Homo sapiens