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 MDPKLLLCLP QGDELFNPLN TMFIQMACIL VFSQLFYLLL KPCGQAGPVA QILAGIVLSP
 61 VLLSRIPKVK EFFLQKNAAD YYSFFSFALR TSFMFLIGLE VDLHFMRRNF KKAAVITLSS
121 FVVSGLLSFA SLMLFIPLFG IKEDYFTFFL VLLVTLSNTA SPVVVRSIAD WKLNTCEIGR
181 LTISCALFIE LTNVVLYTII MAFISGTIIL ELFLFLLATV ALILINMVLA PWLPKRNPKE
241 KYLSKAETLV FFIFLLIIGI TIESYDVNSS VSVFAIGIMF PRQGKTHRTL IQRLSYPIHE
301 FVLPVYFGYI GFRFSIIALT KRFYLGIVII VIVTIAGKFI GVISACMYLK IPKKYWLFLP
361 TILSVKGHVG LLLLDSNYSE KKWWTTTIHD MMVAALVITT LVSGVLASFL LKTREKDFAY
421 EKTSLESHNT NEELRILSCA YGVRHARGAI SLVSALSGSR GASDPFTPLL MHLVPLPKKR
481 KSELMYHEHD EDGGNANGDD EFGTNEGLEI NDSIDSFAKD SKILIQQVKL VTQMLNMHEE
541 ICNATEDLRV SIVFLPFHKH QRIDGKTTND GELFRQMNRN VLRHGPCSIG IFVDRNITGF
601 QQPHGFDSVQ HVATLFFGGP DDREALALCR WLANNTLIHL TVIQFVSEES KAETPVGNAM
661 TRDNNEVFME VLGRNQTEQE TDRSFLEEFY NRFVTTGQVG FIEKLVSNGP HTLTILREIG
721 EMYSLFVVGK STGDCPMTVR MKDWEECPEL GTVGDFLASS LDVNASVLVV QRQRHSHDSF
781 IDD