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TCID	Name	Domain	Kingdom/Phylum	Protein(s)
1.A.112.1.1	Kidney metal (Mg²⁺) transporter, Cyclin (CNN) M2 isoform CRA_b (CNNM2). Defects cause hypomagnesemia. It has an extracellular N-terminus, an N-terminal TMS, a hydrophilic domain followed by 4 TMSs, another hydrophilic domain, and an intracellular C-terminus (de Baaij et al., 2012). CNNM2a forms heterodimers with the smaller isoform CNNM2b. The human splice variant 1 of CNNM2 (ACDP2; Q9H8M5) is a Mg²⁺ transporter (Brandao et al. 2012). The Bateman module is involved in AMP binding and Mg²⁺ sensing, and their binding causes a conformational change in the CBS module, transmitted to the transmembrane domain (Corral-Rodríguez et al. 2014). It may be able to transport divalent metal cations, Mg²⁺, Co²⁺, Mn²⁺, Sr²⁺, Ba²⁺, Cu²⁺, Fe²⁺ and monvalent cation, Na⁺. In prokaryotes, homologs are CorB/C.	Eukaryota	Metazoa	Cyclin M2, CNNM2, of Mus musculus (Q3TWN3)
1.A.112.1.2	Metal transporter CNNM3 (Ancient conserved domain-containing protein 3) (mACDP3) (Cyclin-M3) of 713 aas and probably 5 TMSs with one N-terminal, and four together in the first half of the protein (Chen et al. 2018). See the family description for the domain order of the CNNM proteins.	Eukaryota	Metazoa	CNNM3 of Mus musculus
1.A.112.1.3	Metal transporter CNNM3 (Ancient conserved domain-containing protein 3) (Cyclin-M3). As of 2018, the function of this protein as a Mg²⁺ transporter is under debate (Schäffers et al. 2018).	Eukaryota	Metazoa	CNNM3 of Homo sapiens
1.A.112.1.4	Metal transporter CNNM4 (Ancient conserved domain-containing protein 4) (Cyclin-M4). As of 2018, the function of this protein as a Mg²⁺ transporter was under debate (Schäffers et al. 2018).	Eukaryota	Metazoa	CNNM4 of Homo sapiens
1.A.112.1.5	Mg²⁺ exporter of 951 aas and 5 TMSs in a 1 + 4 TMS arrangement, CNNM1 (Chen et al. 2018).	Eukaryota	Metazoa	CNNM1 of Homo sapiens
1.A.112.1.6	Putative Mg²⁺ exporter of 875 aas and 5 TMSs, CNNM2 or ACDP2 (Chen et al. 2018). The bacterial CorC is involved in resistance to antibiotic exposure and to the survival of pathogenic microorganisms in their host environments. CorC possesses a cytoplasmic region containing the (regulatory ?) ATP-binding site (Huang et al. 2021). An inhibitor, IGN95a, targets the ATP-binding site and blocks both ATP binding and Mg²⁺ export. The cytoplasmic domain structure in complex with IGN95a was determined (Huang et al. 2021). With ATP bound to the cytoplasmic domain, the conformational equilibrium of CorC shifts toward the inward-facing state of the transmembrane domain (Huang et al. 2021). These considerations suggest that CorC may be an ATP-driven Mg²⁺ efflux porter, and if so, the family belongs in TC sub-class, 3.A. CorC homologs may be able to export Mg²⁺, Co²⁺, Mn²⁺, Sr²⁺, Ba²⁺, Cu²⁺ and Fe²⁺.	Eukaryota	Opisthokonta	CNNM2 of Homo sapiens
1.A.112.1.7	Uncharacterized protein of 734 aas and 5 N-terminal TMSs.	Eukaryota	Kinetoplastida	UP of Trypanosoma cruzi
1.A.112.1.8	CNNM Mg²⁺ transport protein of 494 aas and 5 TMSs in a 1 + 4 TMS arrangement. It has a CNNM domain (residues 1 - 220) and three CBS domains, CBS1, 2, and 3 (residues 230 - 425).	Eukaryota	Viridiplantae	CNNM Mg2+ transporter of Arabidopsis thaliana
1.A.112.1.9	CNNM putative Mg²⁺ transport channel of 527 aas with 5 TMSs. The hydrophobic CNNM domain is N-terminal followed by 3 CBS domains.	Eukaryota	Viridiplantae	CNNM of Arabidopsis thaliana
1.A.112.2.1	Uncharacterized protein of 384 aas and 4 TMSs. The region of sequence similarity with established CorC proteins is in a hydrophilic region following the TMSs, putting into question the assignment of this protein to family 9.A.40. The N-terminal domain of 100 aas and 2 TMSs does not show sequence similarity with anything outside of the Candidatus Saccharibacteria bacteria.	Bacteria	Candidatus Saccharibacteria	UP of Candidatus Saccharibacteria bacterium
1.A.112.2.2	Uncharacterized protein of 434 aas with an N-terminal 4 TMSs, YrkA.	Bacteria	Firmicutes	YrkA of Bacillus subtilis (Q45494)
1.A.112.2.3	Probable Mg²⁺ exporter of 452 aas. It does not exhibit hemolysin activity (Sałamaszyńska-Guz and Klimuszko 2008).	Bacteria	Proteobacteria	TylC-like protein of Campylobacter jejuni
1.A.112.2.4	Uncharacterized protein of 444 aas and 4 TMSs, YhdP. Mutations in yhdP increase the activity of sigmaW (Turner and Helmann 2000).	Bacteria	Firmicutes	YhdP of Bacillus subtilis
1.A.112.2.5	CorC homologue, YfjD or YpjE, of 428 aas and 4 TMSs in a 1 + 3 TMS arrangement at the N-terminus of the protein. This hydrophobic region is followed by a larger hydrophilic domain. It is encoded within a two gene operon with YpjD (CorE), a putative cytochrome c assembly protein of 8 or 9 TMSs (P64432; TC# 9.B.14.3.6) (Huang et al. 2021).	Bacteria	Proteobacteria	YfjD of E. coli
1.A.112.2.6	Uncharacterized CorC protein of 327 aas and 3 N-terminal TMSs. The region of sequence similarity with HlyC proteins (TC# 1.C.126) is in a hydrophilic C-terminal region following the TMSs.	Bacteria	Candidatus Saccharibacteria	UP of Candidatus Saccharibacteria bacterium
1.A.112.2.7	Mg²⁺ and Co²⁺ transporter, CorB, of 413 aas and 3 TMSs. It contains DUF21, CBS pair, and CorC-HlyC domainsin succession.	Bacteria	Proteobacteria	CorB of Pseudomonas bauzanensis
1.A.112.2.8	HlyC/CorC family transporter of 354 aas and 4 TMSs.	Bacteria	Actinobacteria	CorC domain protein of Micromonospora peucetia
1.A.112.2.9	Uncharacterized protein of 329 aas and 4 TMSs.	Bacteria	Verrucomicrobia	UP of Verrucomicrobia bacterium
1.A.112.2.10	Magnesium and cobalt efflux protein, CorC or MpfA (Magnesium Protection Factor A) of 449 aas and 4 N-terminal TMSs, apparently in a 2 + 2 TMS arrangement. Evidence has been presented that this protein catalyzes active Mg²⁺ extrusion from the cell (Armitano et al. 2016). If so, It must be an active transporter, either a secondary carrier (TC subclass 2.A) or an ATP hydrolysis-driven exporter (TC subclass 3.A).	Bacteria	Firmicutes	MpfA of Staphylococcus aureus
1.A.112.2.11	PaeA, YtfL, UPF0053 inner membrane protein, Duf21 domain containing protein, HlyC/CorC family transporter, hemolysin homolog of 447 aas and 4 N-terminal TMSs (residues 1 - 200) followed by a large hydrophilic domain (cystathionine beta-synthase, CBS, residues 201 - 447), possibly with a single TMS at about residue 320. It transports cadaverine and putrescine. In fact, Salmonella, Klebsiella pneumoniae (TC# 1.A.112.1.12) and E. coli synthesize, import, and export cadaverine, putrescine, and spermidine to maintain physiological levels of polyamines and provide pH homeostasis. Both low and high intracellular levels of polyamines confer pleiotropic phenotypes or lethality. Iwadate et al. 2021 demonstrated that PaeA (YtfL) is required for reducing cytoplasmic cadaverine and putrescine concentrations. PaeA is involved in stationary phase survival when cells are grown in acidic medium in which they produce cadaverine. The paeA mutant is sensitive to putrescine, but not spermidine or spermine. Sensitivity to external cadaverine in stationary phase is only observed at pH > 8, suggesting that the polyamines need to be deprotonated to passively diffuse into the cell. In the absence of PaeA, intracellular polyamine levels increase and the cells lose viability. Ectopic expression of the known cadaverine exporter, CadB, in stationary phase partially suppresses the paeA mutant phenotype, and overexpression of paeA in exponential phase partially complements a cadB mutant grown in acidic medium. Thus, PaeA is a cadaverine/putrescine exporter, reducing potentially toxic levels under certain stress conditions (Iwadate et al. 2021).	Bacteria	Proteobacteria	PaeA of E. coli
1.A.112.2.12	YtfA, DUF21 domain-containing protein, HlyC/CorC family transporter, magnesium and cobalt efflux protein CorC_2 or CorC_3, of 445 aas and 4 N-terminal TMSs plus a large hydrophilic domain as the C-terminal 250 residues. Based on the E. coli ortholog, it probably transports putrescine and canavanine (Iwadate et al. 2021). Klebsiella pneumoniae is a source of widespread contamination of medical equipment, causing pneumonia as well as other multiorgan metastatic infections. During K. pneumoniae infections of lung epithelia, microtubules are severed and then eliminated, and YtfA plays a role, probably by secreting a relevant compound (Chua et al. 2019).	Bacteria	Proteobacteria	YtfL of Klebsiella pneumoniae