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 MSKLDLEEVN SMQRGKVHGP FLVENMVCQK NHMLTSKGVF LGSDPLKYAM PLMLLQMSVI
 61 IITSRLLYRL LKPLKQGMIS AQVLAGIILG PSLFGQSSAY MQMFLPISGK ITLQTLSNLG
121 FFIHLFLLGL RIDASIIRKA GSKAILIGTA SYALPFSLGN LTVLFLKNTY NLPPDVVHCI
181 STVISLNAMT SFPVTTTVLA ELNILNSDLG RLATNCSIVC EAFSWIVALV FRMFLRDGTL
241 ASVWSFVWVT ALILVIFFVC RPAIIWLTER RSISIDKAGE IPFFPIIMVL LTISLTSEVL
301 GVHAAFGAFW LGVSLPDGPP LGTGLTTKLE MFATSLMLPC FISISGLQTN FFIIGESHVK
361 IIEAVILITY GCKFLGTAAA SAYCNIQIGD AFSLALLMCC QGVIEIYTCV MWKDEKVLNT
421 ECFNLLIITL LLVTGISRFL VVCLYDPSKR YRSKSKRTIL DTRQRNLQFR LLLCVYNVEN
481 VPSMVNLLEA SYPSRFSPIS VFTLHLVELK GRAHAVLVPH HQMNKLDPNT VQSTHIVNGF
541 QRFEQQNQGT LMAQHFTAAA PFSSINDDIC TLALDKKATL IVIPFHKQYA IDGTVDHVNP
601 SIRNINLNVL EKAPCSVGIF IDRGETEGRR SVLMSYTWRN VAVIFIEGRD DAEALAFSMR
661 IAEHPEVSVT MIHFRHKSSL QQNHVVDVES ELAESYLIND FKNFAMSKPK ISYREEIVRD
721 GVETTQVISS LGDSFDLVVV GRDHDLESSV LYGLTDWSEC PELGVIGDMF ASSDFHFSVL
781 VIHQQEGDSL AMDNSYKLPA SPHRVGDPRV HPRFSVEEGF TSVDLHSNR