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.30 The Cation-Chloride Cotransporter Family-- Members of the CCC family, found in animals, plants, fungi and bacteria, can catalyze NaCl/KCl symport, NaCl symport, or KCl symport depending on the system. The NaCl/KCl symporters are specifically inhibited by bumetanide while the NaCl symporters are specifically inhibited by thiazide. Most characterized CCC family proteins are from higher animals, but one has been partially characterized from Nicotiana tabacum (a plant), and homologous ORFs have been sequenced from Caenorhabditis elegans (worm), Saccharomyces cerevisiae (yeast) and Synechococcus sp. (blue green bacterium). The latter proteins are of unknown function. These proteins show some sequence similarity to members of the APC family (TC #2.A.3), but this sequence similarity is insufficient to establish homology. CCC family proteins are usually large (between 1000 and 1200 amino acyl residues), and possess 12 putative transmembrane spanners flanked by large N-terminal and C-terminal hydrophilic domains. Each of the major types of CCC family members in mammals exist as paralogous isoforms. These may differ in substrates transported. For example, of the four currently recognized KCl transporters, KCC1 and KCC4 both recognize KCl with similar affinities, but KCC1 exhibits anion selectivity: Cl- > SCN- = Br- > PO4-3 > I-, while KCl4 exhibits anion selectivity: Cl- > Br- > PO4-3 = I- > SCN-. Both are activated by cell swelling under hypotonic conditions (Mercado et al., 2000).

  1 MDSGDIEEAG GNGEEEFRSG PRLGGSKYRP VVAHDRAVVE MSSIDPGSSS STLKNIKVVA
 61 PGDVGAGVRG PEDGVNGHQK ESKLELFGFD SLVNILGLKS MTGEQIQAPS SPRDGEDISI
121 TQGHPKPPAL KMGTMMGVFV PCLQNILGII YYIRFTWIVG MAGIGQGLVL VFLCGLCTFL
181 TTISLSAIAT NGAMKGGGPY YLIGRALGPE VGISIGLCFF LGNAVAGALY VLGAVETFLK
241 AFPAAGIFRE TITKVNGTAV SESIQSPNSH DLQVYGIVVT ILLCFIVFGG VKMINRVAPA
301 FLVPVLLSIF CIFIGIFLAK TDDPDNGITG LRLKSFKDNW GSAYQMTNDA GIPDPTGGTY
361 WSFNELVGLF FPAVTGIMAG SNRSASLKDT QKSIPVGTLA ATLTTTSLYL ISVLFFGAVA
421 TRDKLLTDRL LTATIAWPFP AIVHVGIILS TLGAALQSLT GAPRLLAAIA NDDILPILNY
481 FKVADTSEPH IATLFTAFIC IGCVVIGNLD LITPTVTMFY LLCYSGVNLS CFLLDLLDAP
541 SWRPRWKYHH WSLSFVGASL CIVIMFLISW SFTVVAIALA SLIYKYVGLK GKAGDWGDGF
601 KSAYFQLALR SLRSLGANQV HPKNWYPIPL VFCRPWGQLP ENVPCHPKLA DFANCMKKKG
661 RGMSIFVSIL DGDYYECAEE AKEACKQLAT YIEYKRCEGV AEIVVAPNMT EGFRGIIQTM
721 GLGNLKPNIV VMRYPEIWRR ENLTEIPSTF VGIINDCITA NKAVVIIKGL DEWPNEYQRQ
781 YGTIDLYWIV RDGGLMLLLS QLLLTKESFE SCKIQLFCIA EEDSDAEALK ADVKKFLYDL
841 RMHAEVIVVT MKSWDIRSEG NSQEDSLEAF DAAQRRISDY LGEIKRQGSN PLLANGKPMV
901 VNEQQVEKFL YTMLKLNSTI LSYSRMAAVV LVSLPPPPLN HPAYFYMEYM DLLVENVPRM
961 LIVRGYHRDV VTLFT