Monovalent cation:proton antiporter-3
The Monovalent Cation (K or Na):Proton Antiporter-3 (CPA3) Family (TC# 2.A.63) is a member of the Na transporting Mrp superfamily. The CPA3 family consists of bacterial multicomponent K:H and Na:H antiporters. The best characterized systems are the PhaABCDEFG system of "Sinorhizobium meliloti" (TC# 2.A.63.1.1) that functions in pH adaptation and as a K efflux system, and the MnhABCDEFG system of "Staphylococcus aureus" (TC# 2.A.63.1.3) that functions as a Na efflux Na:H antiporter. Homology. A homologous, but only partially sequenced, system was earlier reported to catalyze Na:H antiport in an alkalophilic "Bacillus" strain . PhaA and PhaD are respectively homologous to the ND5 and ND4 subunits of the H-pumping (TC #3.D.1). Homologous protein subunits from "E. coli" NADH:quinone oxidoreductase can functionally replace MrpA and MrpD in "Bacillus subtilis." Homologues of PhaA, B, C and D and Nha1, 2, 3 and 4 of an alkalophilic "Bacillus" strain are the Yuf(Mrp)T, U, V and D genes of "Bacillus subtilis". In this system, YufT is believed to be responsible for Na:H antiporter activity, but it does not have activity in the absence of other constituents of the operon. Structure. The seven Pha proteins are  of the following sizes (in #aas) and exhibit the following putative numbers of transmembrane α-helical spanners (TMSs): All are predicted to be integral membrane proteins. Corresponding values for the "S. aureus" Mnh system are: In view of the complexity of the system, large variation in subunit structure, and the homology with NDH family protein constituents, a complicated energy coupling mechanism, possibly involving a redox reaction, cannot be ruled out. Function. Na or Li does, but K, Ca, and Mg do not, support significant antiport by the Gram-positive bacterial systems (TC# 2.A.6.3.1.2 and TC# 2.A.6.3.1.3). Na(Li)/H antiporters have  alkaline pH optima and apparent K values for Na that are among the lowest reported for bacterial Na/H antiporters. Na/Hantiport consumes the pmf and therefore is probably electrogenic. YufF (MrpF) appears to catalyze cholate efflux, possibly by a Na symport mechanism. It plays a major role in Na extrusion and is required for initiation of sporulation. Additionally, another component of the operon, MrpF (equivalent to PhaF of "R. meliloti") has been implicated in choline and Na efflux. The MrpA-G proteins of "B. subtilis" have been shown to be present in a single multicomponent complex. They provide Na /H antiport activity and function in multiple compound resistance and pH homeostasis. Transport Reaction. The generalized reaction believed to be catalyzed by CPA3 family members is:[K or Na] (in) + H (out) ⇌ [K or Na] (out) + H (in).