Table 8 APC family member representation in Sco and Mxa TC # Family Sco Mxa 2.A.3 Amino Acid-Polyamine-Organocation (APC) Superfamily 17 2 2.A.15 Betaine/PND-1186 mw Carnitine/Choline Transporter (BCCT) Family 1   2.A.18 Amino Acid/Auxin Permease (AAAP) Family     2.A.21 Solute:Sodium

Symporter (SSS) Family 8 4 2.A.22 Neurotransmitter:Sodium Symporter (NSS) Family     2.A.25 Alanine or Glycine:Cation Symporter (AGCS) Family 1   2.A.30 Cation-Chloride Cotransporter (CCC) Family     2.A.39 Nucleobase:Cation Symporter-1 (NCS1) Family 5   2.A.42 Hydroxy/Aromatic Amino Acid Permease (HAAAP) Family     Numbers of APC Superfamily proteins in Sco and Mxa are arranged by family. The SSS Family of solute:Na+ symporters, a constituent BACE inhibitor member of the APC Superfamily [59], transports a wide variety of solutes. Of the eight SSS family members in Sco, five probably transport short monocarboxylic acids (acetate, lactate, pyruvate, etc.), while three probably transport sugars. Of the four hits in Mxa, two may be monocarboxylate transporters while the other two are probably

non-transporting signal transduction proteins with C-terminal sensor kinase domains. Only one of them is homologous to SSS transporters in its transmembrane domain. Heavy metal carriers Both Sco and Mxa have members (five and three members, respectively) of the heavy metal efflux Cation Diffusion Facilitator (CDF) Family 2.A.4; [60], but only Mxa has members (two) of the metal uptake Zinc-Iron Permease (ZIP) Family 2.A.5; [61]. Only Sco has a member of the Nramp Family Proteases inhibitor of divalent cation transporters. These proteins exhibit varying specificities for heavy metals and are involved in metal ion homeostasis. Heavy metal transporters are also found in other families such as the RND very Superfamily. The RND superfamily The RND Superfamily 2.A.6; [62, 63] is well represented in both Sco and Mxa with 16 members in Sco and 20 in Mxa. Family 1 (Heavy Metal Efflux (HME)) is prevalent in Mxa with six members (see TCDB; 2.A.6.1.7-11 and 2.A.6.3.2), but absent in Sco. Based on induction properties, one may export

Zn2+, two may export heavy metals (one of these is induced under starvation conditions), and three may export copper [64]. Similarly, the (largely Gram-negative bacterial) Hydrophobe/Amphiphile Efflux-1 (HAE1) Family (Family 2), usually considered to be concerned with drug export, is found in Mxa (four members) but not Sco. Surprisingly, the lipooligosaccharide Nodulation Factor Exporter (NFE) Family (Family 3) is represented in both organisms, but with six members in Mxa and only one in Sco. These proteins may transport substrates resembling rhizobial nodulation factor lipooligosaccharides, which are the substrates of the only characterized member of the NFE Family [65]. Such substrates are not known to be present in myxobacteria or actinobacteria.