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TCID	Name	Domain	Kingdom/Phylum	Protein(s)
1.A.77.1.1	Inner membrane 40KD mitochondrial Ca²⁺channel-forming uniporter, MCU or MICU2 (DUF607; 350 aas; coiled coil domain protein 109 A) (De Stefani et al., 2011; Drago et al., 2011). It functions with MICU1, an essential component of the system, as well as the gatekeeper for Ca²⁺uptake (Mallilankaraman et al. 2012a; Mallilankaraman et al. 2012b). It contributes to metabolism-insulin secretion coupling in clonal pancreatic beta-cells (Alam et al. 2012). MCU-mediated Ca²⁺ uptake in beta cells is essential to establish a nutrient-induced mitochondrial pH gradient which is critical for sustained ATP synthesis and metabolism-secretion coupling in insulin-releasing cells (Quan et al. 2015). The mitochondrial calcium uniporter of pulmonary type 2 cells determines the severity of acute lung injury (Islam et al. 2022). Regulation of mitochondrial calcium uptake by the mitochondrial calcium uniporter complex is crucial for heart function. It has been demonstrated that mitochondrial calcium uptake (MICU)1 and MICU2, regulatory subunits of the complex, help maintain calcium homeostasis in cardiac mitochondria, provide potential targets for therapies aimed at improving mitochondrial function in heart disease (Ozkurede et al. 2024).	Eukaryota	Metazoa, Chordata	MCU of Mus musculus (Q3UMR5)
1.A.77.1.2	MCU homologue of 338 aas and 2 TMSs.	Eukaryota	Viridiplantae, Streptophyta	MCU homologue of Arabidopsis thaliana (Q1PE15)
1.A.77.1.3	Algal MCU homologue (300 aas; 2 TMSs)	Eukaryota	Viridiplantae, Chlorophyta	MCU homologue of Chlamydomonas reinhardtii (A8J6W0)
1.A.77.1.4	Slime mold MCU homologue of 275 aas and 2 TMSs. The structure of the N-terminal domain (NTD) has been solved at 1.7 A resolution (Yuan et al. 2020). The oligomeric DdMCU-NTD contains four helices and two strands arranged in a fold that is completely different from the known structures of other MCU-NTD homologues. This domain may regulate channel activity (Yuan et al. 2020).	Eukaryota	Evosea	MCU homologue of Dictyostellium discoideum (Q54LT0)
1.A.77.1.5	Fungal MCU homologue of 493 aas and 2 TMS. The cryo-electron microscopy structure of the full-length MCU to an overall resolution of ~3.7 Å has been determined (Yoo et al. 2018). The structure reveals a tetrameric architecture, with the soluble and transmembrane domains adopting different symmetric arrangements within the channel. The conserved W-D-Phi-Phi-E-P-V-T-Y sequence motif of the MCU pore forms a selectivity filter comprising two acidic rings separated by one helical turn along the central axis of the channel pore (Yoo et al. 2018).	Eukaryota	Fungi, Ascomycota	MCU homologue of Neurospora crassa (Q7S4I4)
1.A.77.1.6	MCU homologue of 355 aas; 4 TMSs (2+2) (Docampo et al. 2013).	Eukaryota	Euglenozoa	MCU homologue of Trypanosoma cruzi (E7KWU4)
1.A.77.1.7	Mitochondrial Ca²⁺ Uniporter, a channel complex. MCU is a putative 5TMS protein (307 aas) with homology to MCU Ca²⁺/Mg²⁺ channels in the C-terminal 2TMS domain. The N-terminal domain is found only in Trypanosoma and Leishmania species. The TbMCU complex possesses four subunits, MCU (307 aas), MCUb (214 aas), MCUc (254 aas) and MCUd (249 aas)), present only in trypanosomatids and required for Ca²⁺ transport. These four subunits interact through their transmembrane helices to form hetero-oligomers in a ~380 KDa complex (Huang and Docampo 2018).	Eukaryota	Euglenozoa	Channel homologues of Trypanosoma brucei MCU MCUb MCUc MCUd
1.A.77.1.8	Ciliate MCU homologue 362 aas; 2 TMSs	Eukaryota	Ciliophora	MCU homologue of Paramecium tetraurelia (A0E7U6)
1.A.77.1.9	MCU homologue (766 aas; 2 TMSs)	Bacteria	Bacteroidota	MCU homologue of Cytophaga hutchinsonii (Q11Z39)
1.A.77.1.10	MCU homologue (355 aas; 2 TMSs)	Bacteria	Chlorobiota	MCU homologue of Chlorobium phaeobacteroides (A1BIL6)
1.A.77.1.11	Mitochondrial calcium uniporter, MCU, of 362 aas	Eukaryota	Ciliophora	MCU of Tetrahymena thermophila
1.A.77.1.12	The mitochondrial calcium uniporter regulatory subunit MCUb of 336 aas; part of the MCU complex (Sancak et al. 2013). MCU regulates procoagulant platelet formation (Kholmukhamedov et al. 2018) and interacts with the c-subunit of the mitochondrial ATPase (Huang and Docampo 2020). It functions in animals (but not in fungi or protozoans) with another protein, EMRE or SMDT1 of 107 aas (TC# 8.A.45.1.1) that interacts with and renders the channel functional (MacEwen et al. 2020). The mitochondrial calcium uniporter of pulmonary type 2 cells determines the severity of acute lung injury (Islam et al. 2022). Metal coordination complexes, particularly multinuclear ruthenium complexes, are the most widely investigated MCU inhibitors due to both their potent inhibitory activities as well as their longstanding use for this application (Huang and Wilson 2023).	Eukaryota	Metazoa, Chordata	MCUb of Homo sapiens
1.A.77.1.13	Mitochondrial calcium uniporter of 658 aas (Docampo et al. 2013).	Eukaryota		MCU of Monosiga brevicollis
1.A.77.1.14	Mitochondrial calcium uniporter of 297 aas.	Eukaryota	Euglenozoa	MCU of Leishmania donovani
1.A.77.1.15	MCU of 488 aas and 2 TMSs. The 3.8 Å cryoEM structure has been solved (Nguyen et al. 2018). The channel is a homotetramer with two-fold symmetry in its amino-terminal domain (NTD) that adopts a structure similar to that of human MCU. The NTD assembles as a dimer of dimers to form a tetrameric ring that connects to the transmembrane domain through an elongated coiled-coil domain. The ion-conducting pore domain maintains four-fold symmetry, with the selectivity filter positioned at the start of the pore-forming TM2 helix. The aspartate and glutamate sidechains of the conserved DIME motif are oriented towards the central axis and separated by one helical turn (Nguyen et al. 2018).	Eukaryota	Fungi, Ascomycota	MCU of the fungus, Neosartorya fischeri
1.A.77.1.16	Mitochondrial calcium uniporter protein, MCU, of 302 aas and 2 TMSs. It interacts with subunit c of the ATP synthase (Huang and Docampo 2020).	Eukaryota	Euglenozoa	MCU of Trypanosoma cruzi
1.A.77.1.17	CMU of 248 aas and 2 TMSs. It functions together with the EMRE regulatory protein (TC#8.A.45.1.6). MCU and EMRE form the minimal functional unit of the mitochondrial calcium uniporter complex in metazoans. Wang et al. 2020 functionally reconstituted an MCU-EMRE complex from the red flour beetle, Tribolium castaneum, and determined a cryo-EM structure of the complex at 3.5 Å resolution. They demonstrated Ca²⁺ uptake into proteoliposomes containing the purified complex. Uptake depended on EMRE as well as cardiolipin. The structure revealed a tetrameric channel with a single ion pore. EMRE was located at the periphery of the transmembrane domain and associates primarily with the first TMS of MCU. Coiled-coil and juxtamembrane domains within the matrix portion of the complex adopt markedly different conformations than in a structure of a human MCU-EMRE complex, suggesting that the structures represent different conformations of these functionally similar metazoan channels (Wang et al. 2020).	Eukaryota	Metazoa, Arthropoda	Mcu of Tribolium castaneum
1.A.77.2.1	Putative Mg²⁺ transporter, AtpZ	Bacteria	Campylobacterota	AtpZ of Helicobacter pylori (Q1CUJ6)
1.A.77.2.2	AtpZ homologue (125 aas; 2 TMSs)	Bacteria	Myxococcota	AtpZ homologue of Anaeromyxobacter sp. Fw109-5 (A7HIX1)
1.A.77.2.3	AtpZ of 92 aas	Bacteria	Thermodesulfobacteriota	AtpZ of Desulfovibrio vulgaris (A1VF64)
1.A.77.2.4	AtpZ of 106 aas	Bacteria	Chlorobiota	AtpZ of Chlorobium tepidum (Q8KGE5)
1.A.77.2.5	AtpZ of 105 aas			AtpZ of Rhodomicrobium vannielii (E3I7U2)
1.A.77.2.6	AtpZ of 108 aas	Bacteria	Pseudomonadota	AtpZ of Maricaulis maris (Q0AMJ5)
1.A.77.2.7	ATP synthase protein Z of 114 aas	Bacteria	Pseudomonadota	AtpZ of Rhodobacter capsulatus
1.A.77.2.8	The Mg²⁺ uptake channel, AtpZ. Postulated to form homo- and/or hetero oligomers [(AtpZ)n-x (AtpI)x] (Hicks et al., 2003). The AtpI homologue (P22475) is in subfamily 1.A.77.3 and has TC# 1.A.77.3.1.	Bacteria	Bacillota	The AtpZI Mg²⁺/Ca²⁺ channel of Bacillus pseudofirmus AtpZ (Q9EXJ9)
1.A.77.2.9	AtpZ of 112 aas.	Archaea	Euryarchaeota	AtpI of Methanosarcina acetivorans (Q8TN54)
1.A.77.2.10	AtpZ homologue of 87 aas.	Bacteria	Campylobacterota	AtpZ of Hippea maritima
1.A.77.2.11	AtpZ homologue of 90 aas	Bacteria	Campylobacterota	AtpZ of Campylobacter curvus
1.A.77.2.12	AtpZ homologue of 60 aas	Archaea	Euryarchaeota	AtpZ homologue of Methanothermococcus okinawensis
1.A.77.2.13	AtpZ homologue of 80 aas	Bacteria	Thermodesulfobacteriota	AtpZ of Geobacter metallireducens
1.A.77.2.14	AtpZ homologue of 105 aas	Bacteria	Pseudomonadota	AtpZ of Acidophilium multivorum
1.A.77.2.15	AtpZ homologue of 96 aas	Bacteria	Pseudomonadota	AtpZ of Tistrella mobilis
1.A.77.2.16	Putative Mg²⁺ channel of 113 aas and 2 TMSs. Part of the F-type ATPase (Morales-Rios et al. 2015).	Bacteria	Pseudomonadota	Magnesium channel of Paracoccus denitrificans
1.A.77.2.17	Putative Mg²⁺ channel, AtpI, that functions with a Na⁺-transporting F-type ATPase (Soontharapirakkul et al. 2011).	Bacteria	Cyanobacteriota	AtpI of Aphanothece halophytica
1.A.77.3.1	AtpI of 133 aas, This protein is a part of a two component channel and as such is also listed with TC# 1.A.77.2.8.	Bacteria	Bacillota	AtpI of Bacillus pseudofirmus
1.A.77.3.2	ATP synthase protein I	Bacteria	Bacillota	AtpI of Bacillus subtilis
1.A.77.3.3	ATP synthase subunit I	Bacteria	Thermodesulfobacteriota	AtpI of Desulfococcus oleovorans
1.A.77.3.4	ATP synthase protein I	Bacteria	Bacillota	AtpI of Bacillus megaterium
1.A.77.3.5	AtpI homologue	Bacteria	Bacillota	AtpI homologue of Coprococcus catus
1.A.77.3.6	AtpI homologue of 122aas and 4 TMSs	Bacteria	Bacillota	AtpI homologue of Paenibacillus mucilaginosus
1.A.77.3.7	ATP synthase protein I	Bacteria	Pseudomonadota	AtpI of Vibrio cholerae serotype O1
1.A.77.3.8	AtpI homologue of 150 aas	Bacteria	Pseudomonadota	AtpI of Klebsiella pneumoniae
1.A.77.3.9	AtpI homologue of 135 aas	Bacteria	Pseudomonadota	AtpI of Pseudomonas putida
1.A.77.3.10	AtpI homologue of 126 aas	Bacteria	Pseudomonadota	AtpI of Ferrimonas balearica
1.A.77.3.11	AtpI of 126 aas	Bacteria	Pseudomonadota	AtpI of E. coli
1.A.77.3.12	AtpI homologue of 185 aas	Bacteria	Pseudomonadota	AtpI of Ralstonia solanacearum
1.A.77.3.13	ATP synthase protein I	Bacteria	Mycoplasmatota	AtpI of Mycoplasma gallisepticum )
1.A.77.3.14	ATP synthase I, AtpI	Bacteria	Bacillota	AtpI of Acetohalobium arabaticum
1.A.77.3.15	ATP synthase subunit I	Bacteria	Thermodesulfobacteriota	AtpI of Geobacter uraniireducens
1.A.77.3.16	ATP synthase I	Bacteria	Thermotogota	AtpI of Fervidobacterium pennivorans
1.A.77.3.17	AtpI of the Na⁺ ATPase. Essential for assembly of the c-ring of the rotor (Brandt et al. 2013).	Bacteria	Bacillota	AtpI of Acetobacterium woodii
1.A.77.3.18	AtpI homologue of 122 aas and 4 TMSs	Bacteria	Bacillota	AtpI homologue of Clostridium sticklandii
1.A.77.3.19	AtpI homologue of 109 aas	Bacteria	Thermotogota	AtpI of Thermatoga thermarum
1.A.77.3.20	ATP synthase, subunit I of 117 aas and 4 TMSs	Bacteria	Bacillota	AtpI of Staphylococcus aureus
1.A.77.3.21		Bacteria	Cyanobacteriota	AtpI of Synechococcus sp.
1.A.77.3.22	ATP snthase subunit I, AtpI of 147 aas	Bacteria	Bacillota	AtpI of Halothermothrix orenii
1.A.77.3.23	ATP synthase, subunit I, AtpI of 153 aas	Bacteria	Actinomycetota	AtpI of Mycobacterium leprae
1.A.77.3.24	AtpI of 255 aas and 4 TM	Eukaryota	Rhodophyta	AtpI of Galdieria sulfuraria
1.A.77.3.25	Putative AtpI of 122 aas and 4 TMSs	Bacteria	Deferribacterota	AtpI of Denitrovibrio acetophilus
1.A.77.3.26	Uncharacterized protein of 189 aas and 5 TMSs	Bacteria	Myxococcota	UP of Anaeromyxobacter dehalogenans
1.A.77.3.27	AtpI homologue of 133 aas	Bacteria	Fusobacteriota	AtpI of Leptotrichia buccalis
1.A.77.3.28	AtpI homologue of 126 aas	Bacteria	Fusobacteriota	AtpI of Ilyobacter polytrophus
1.A.77.3.29	AtpI homologue of 127 aas	Bacteria	Fusobacteriota	AtpI of Propionigenium modestum
1.A.77.3.30	AtpI homologue of 135 aas	Bacteria	Fusobacteriota	AtpI of Sebaldella termitidis
1.A.77.3.31	AtpI homologue of 164aas and 4 TMSs	Bacteria	Mycoplasmatota	AtpI of Mycoplasma fermentans
1.A.77.3.32	AtpI homologue of 150 aas	Bacteria	Mycoplasmatota	AtpI of Mycoplasma arthritidis
1.A.77.3.33	AtpI homologue of 161 aas. Immunogenic proteins have been evaluated as vaccine candidates against Mycoplasma synoviae (Zhang et al. 2023).	Bacteria	Mycoplasmatota	AtpI of Mycoplasma synoviae
1.A.77.3.34	AtpI of 140 aas and 4 TMSs	Bacteria	Thermodesulfobacteriota	AtpI of Desulfotalea psychrophila
1.A.77.3.35	Putative AtpI of 129 aas and 4 TMSs	Bacteria	Bacillota	AtpI of Heliobacterium modesticaldum
1.A.77.3.36	Putative AtpI of 139 aas and 4 TMSs	Bacteria	Acidobacteriota	AtpI of Candidatus Koribacter versatilis
1.A.77.3.37	Putative AtpI of 133 aas and 4 TMSs	Bacteria	Thermodesulfobacteriota	AtpI of Desulfobacula toluolica
1.A.77.3.38	Putative AtpI of 140 aas and 4 TMSs	Bacteria	Thermodesulfobacteriota	AtpI of Syntrophus aciditrophicus
1.A.77.3.39	Putative AtpI of 256 aas and 4 or 5 TMSs. The N-terminus may include a single TMS plus a hydrophilic domain before the C-terminal AtpI domain.	Eukaryota	Rhodophyta	AtpI of Chondrus crispus
1.A.77.3.40	AtpI of 156 aas and 4 TMSs	Eukaryota	Cercozoa	AtpI of Paulinella chromatophora
1.A.77.3.41	Putative AtpI of 119 aas and 4 TMSs	Bacteria	Deferribacterota	AtpI of Deferribacter desulfuricans
1.A.77.3.42	Putative AtpI of 138 aas and 4 TMSs	Bacteria	Fibrobacteres/Acidobacteria group	AtpI of Granulicella tundricola
1.A.77.3.43	Putative AtpI of 121 aas and 4 TMSs	Bacteria	Nitrospirota	AtpI of Thermodesulfovibrio yellowstonii
1.A.77.3.44	Putative AtpI of 160 aas and 4 TMSs	Bacteria	Mycoplasmatota	AtpI of Mycoplasma mobile
1.A.77.3.45	ATP synthase I-like protein, AtpI, of 385 aas amd 3 - 4 TMSs.	Eukaryota	Viridiplantae, Chlorophyta	AtpI of Chlamydomonas reinhardtii (Chlamydomonas smithii)
1.A.77.4.1	Fusion protein with N-terminal 4 TMS AtpI domain and large soluble C-terminal α/β-hydrolase domain.	Eukaryota	Rhodophyta	Fusion protein of Galdieria sulphuraria
1.A.77.4.2	Fusion protein with N-terminal 4 TMS AtpI domain and large soluble C-terminal α/β-hydrolase domain.	Eukaryota	Evosea	Fusion protein of Dictyostelium discoideum
1.A.77.4.3	Fusion protein with N-terminal 4 TMS AtpI domain and large soluble C-terminal α/β-hydrolase domain.	Eukaryota	Evosea	Fusion protein of Entamoeba histolytica
1.A.77.5.1	AtpI homologue of 147 aas and 4 TMSs. Deletion of the gene encoding the ortholog, cg1360, affects ATP synthase function and enhances production of L-Valine in Corynebacterium glutamicum (Wang et al. 2019).	Bacteria	Actinomycetota	AtpI of Corynebacterium diphtheriae
1.A.77.5.2	AtpI homologue of 137 aas	Bacteria	Actinomycetota	AtpI of Streptomyces avermitilis
1.A.77.5.3	AtpI homologue of 145 aas	Bacteria	Actinomycetota	AtpI of Frankia alni
1.A.77.5.4	Putative AtpI of 177 aas and 4 TMSs	Bacteria	Actinomycetota	AtpI of Saccharomonospora cyanea
1.A.77.5.5	Putative ATP synthase protein I2 of 161 aas and 4 TMSs	Bacteria	Actinomycetota	Putative reductase of Actinokineospora spheciospongiae
1.A.77.5.6	Uncharacterized protein of 157 aas and 3-4 TMSs	Bacteria	Actinomycetota	UP of Cellulomonas fimi