Electrochemical Potential-driven Transporters - Class 3-- Secondary carrier-type facilitators. Transport systems are included in this category if they utilize a carrier-mediated process to catalyze uniport (a single species is transported by facilitated diffusion in a process not coupled to the utilization of a primary source of energy), antiport (two or more species are transported in opposite directions in a tightly coupled process not directly linked to a form of energy other than chemiosmotic energy) and/or symport (two or more species are transported together in the same direction in a tightly coupled process not directly linked to a form of energy other than chemiosmotic energy). These systems are usually stereospecific. Solute:solute countertransport is a characteristic feature of secondary carriers.

Porters(uniporters,symporters,antiporters)-- Transport systems are included in this subclass if they utilize a carrier-mediated process to catalyze uniport (a single species is transported either by facilitated diffusion or in a membrane potential-dependent process if the solute is char ged), antiport (two or more species are transported in opposite directions in a tightly coupled process, not coupled to a direct form of energy other than chemiosmotic energy) and/or symport (two or more species are transported together in th e same direction in a tightly coupled process, not coupled to a direct form of energy other than chemiosmotic energy).

2.A.37 The Monovalent Cation:Proton Antiporter-2 Family-- The CPA2 family is a moderately large family (over 100 sequenced members) from bacteria, archaea and eukaryotes. Among the functionally well-characterized members of the family are (1) the KefB/KefC K+ efflux proteins of E. coli which may be capable of catalyzing both K+/H+ antiport and K+ uniport, depending on conditions (Bakker et al., 1987; Booth et al., 1996; Munro et al., 1991), (2) the Na+/H+ antiporter of Enterococcus hirae(Waser et al., 1992) and (3) the K+/H+ antiporter of S. cerevisiae. It has been proposed that under normal physiological conditions, these proteins may function by essentially the same mechanism (Reizer et al., 1992). KefC and KefB of E. coli are responsible for glutathione-gated K+ efflux (Ferguson et al., 1993, 1997). Each of these proteins consists of a transmembrane hydrophobic N-terminal domain, and a less well-conserved C-terminal hydrophilic domain. Each protein interacts with a second protein encoded by genes that overlap the gene encoding the primary transporter. The KefC ancillary protein is YabF while the KefB ancillary protein is YheR. These ancillary proteins stimulate transport activity about 10-fold (Miller et al., 2000). These proteins are important for cell survival during exposure to toxic metabolites, possibly because they can release K+, allowing H+ uptake. Activation of the KefB or KefC K+ efflux system only occurs in the presence of glutathione and a reactive electrophile such as methylglyoxal or N-ethylmaleimide. Formation of the methylglyoxal-glutathione conjugate, S-lactoylglutathione, is catalyzed by glyoxalase I, and S-lactoylglutathione activates KefB and KefC (MacLean et al., 1998). H+ uptake (acidification of the cytoplasm) accompanying or following K+ efflux may serve as a further protective mechanism against electrophile toxicity (Booth et al., 1996; Ferguson et al., 1993, 1997; Stumpe et al., 1996).

  1 MNSTTTKNVC GDKWYLNLDR PEEALKILVF IAIFVVRTLL HYLMKPLGQP YLTTDFAIGL
 61 ILGNIPRFRG AFSGPYSITL NNIIEFGMIC HMFVMGLEMN PSVLLRPPTK DAFIAYTSMI
121 TTFVLAFVTT PFLHYTKTSP YIFSLALSLM ASSTGSPILT RVIANLKIRK SDLGKLASAA
181 GVHTDMISTL LYCFGFIFFP TEKPLARPLH RFFRALLMFC LFLAQVTFTS IVSPIFLNWV
241 NNENPEGKPL KGSHLVMSLA FVVLICSFPT WPPESMYNPI LSAFTAGLFL PNKGRMSKWI
301 INKINYLLST VFYPIFFFWV GFIIHMRNFD ITDKMAWVRF FSLLGTVIAG KVTGTVLCGL
361 LLGYHVPETA SLGLLLTTKG HFHVYLAALA IRTNRVKSTT GALIIFIIVF TVVYSPFVVM
421 DIIKRARKRV PVHIMALQWL DPTTELRILI GLHGPHNIGS TLNVMEICHG GREPGSIFYA
481 TDMVELTDEI AATLKKGGGA GQSNDSVTVT DRSVTEMRES ITAAVNGYGE LRNGQGVTVR
541 RMLALSTFVT MAHDVCGLAD ELMVSIIILP FHKRLNPDGT LDAGHAGFRH VNRKILKNAP
601 CSVGILVDRS FGQTEEAWRP GASMGIAIIF IGGRDDREAL AFAAQVARHP AVKLKVIRFL
661 EDKSSQNAQK RSSILNRASV VDQEEEMKLD DECFAEFYER YIAGGGRVSY MEKHLTNSSE
721 TFTALKSLDG EYGLVIVGRG GGRASSGLTT GLNDWQQCPE LGPIGDVLSG SDFSHNTSML
781 IIQQQRTRGQ LEGLHDDFTI L