Classification of Membrane Transport Proteins

Continued from properties of families 1

Properties of Families of Transport Proteins Included in the TC System (continued)

2. Electrochemical-Potential-Driven Transporters

2.A Transporters or carriers (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 mediated diffusion or in a membrane-potential-dependent manner if the solute is charged), antiport (two or more species are transported in opposite directions in a tightly coupled process, not utilizing chemical free energy), or symport (two or more species are transported together in the same direction in a coupled process, again not utilizing any form of energy other than the electrochemical potential gradient).

TC no. a Family Substrates b Size range c Number of transmembrane segmentsd Distributione nf Examples
2.A.1MFSnumerous small molecules (also can serve as receptors) 300-12506, 12 or 14A, B, E3lactose transporter or permease LacY of Escherichia coli; drug efflux transporter or permease EmrD of Escherichia coli
2.A.2GPH sugars (glycosides)250-6501A, B, E2melibiose transporter or permease MelB of Escherichia coli
2.A.3 APC amino acids, polyamines, organic cations (also can serve as receptors)400-125010, 12, 14A, B, E2lysine transporter or permease LysP of Escherichia coli
2.A.4CDF Cd2+, Co2+, Ni2+300-7506A, B, E2heavy metal uptake and efflux transporters of bacteria, eukaryotic plasma membranes and mitochondria (CzcD of Ralstonia eutropha)
2.A.5ZIP Zn2+; Fe2+3768E2zinc uptake transporter Zrt1 of Saccharomyces cerevisiae
2.A.6RND heavy metal ions; multiple drugs; oligosaccharides; organic solvents, fatty acids; phospholipids, cholesterol 800-12006, 12A, B, E3drug efflux pump AcrA of Escherichia coli
2.A.7DMT multiple drugs; sugars and derivatives; nucleotides, nucleotide sugars100-500(4)2, (5)2, 10B3cationic drug efflux pump Smr of Staphylococcus aureus
2.A.8GntP gluconate, idonate400-500c. 12-14B2gluconate permease GntP of Bacillus subtilis
2.A.9Oxa1 proteins 350-4505B, E1Oxalp of Saccharomyces cerevisiae
2.A.10KDGT D-erythro-3-deoxyhexulosonate g300-40010-12B12-keto-3-deoxygluconate transporter KdgT of Erwinia chrysanthemi
2.A.11CitMHS citrate-M2+400-45012 B1citrate,Me2+/H+ symporter CitM of Bacillus subtilis
2.A.12AAA ATP, ADP450-65012B, E(Pl)1ATP/ADP exchange translocator of Rickettsia prowazekii
2.A.13Dcu C4-dicarboxylates440 10, 12B(G-)1dicarboxylate uptake porter-A DcuA of Escherichia coli
2.A.14LctP lactate 450-60012A, B1lactate transporter LctP of Escherichia coli
2.A.15BCCT glycine; betaine; carnitine; choline; multiple organic cations450-70012B2carnitine transporter CaiT of Escherichia coli
2.A.16TDT tellurite; dicarboxylates300-35010A, B, E1tellurite uptake transporter TehA of Escherichia coli
2.A.17POT peptides; nitrates; amino acids 450-80012B, E2dipeptide transporter DtpT of Lactococcus lactis
2.A.18AAAP amino acids and their derivatives400-75011E2amino acid/auxin,H+ symporter Aux-1 of Arabidopsis thaliana
2.A.19CaCA Ca2+350-40010 or 11A, B, E2Ca2+:H+ antiporter ChaA of Escherichia coli
2.A.20PiT inorganic phosphate; sulfate 400-70010-12A, B, E2phosphate transporter PitA of Escherichia coli
2.A.21SSS sugars; amino acids; vitamins; nucleosides; inositols; iodide, organic and inorganic anions; urea; organic cations (also can serve as receptors)400-75012-15A, B, E2pantothenate,Na+ symporter PanF of Escherichia coli
2.A.22NSS neurotransmitters (often amino acids); osmolytes; taurine; creatine600-75012A, B, E (An) 3serotonin,Na+ symporter of Homo sapiens
2.A.23DAACS C4-dicarboxylates; acidic and neutral amino acids400-6008-10A, B, E2glutamate/aspartate porter GltP of Escherichia coli
2.A.24CCS mono-, di- and tricarboxylates 400-45012B1citrate,Na+ symporter CitS of Klebsiella pneumoniae
2.A.25AGCS alanine, glycine 400-5508-12B2alanine/glycine transporter DagA of Alteromonas haloplanktis
2.A.26LIVCS branched-chain amino acids, Leu, Ile, Val400-45012B1branched-chain amino acid transporter BraB of Pseudomonas aeruginosa
2.A.27ESS glutamate c. 40010B1glutamate,Na+ symporter GltS of Escherichia coli
2.A.28BASS bile acids350-5007B, E (An)1bile acid uptake system of Rattus norvegicus
2.A.29MC ATP/ADP/AMP; Pi; organic anions; H+; carnitine/acyl carnitine; basic amino acids; FAD 300-7506E (Mito)3ADP/ATP exchanger of Homo sapiens in mitochondria and peroxisomes
2.A.30CCC K+, Na+, Cl-; KCl; NaCl1000-120012A, B, E2NaCl,KCl cotransporter of Rattus norvegicus
2.A.31AE inorganic anions 900-125014E2anion exchanger AE1 of Homo sapiens
2.A.32Sit silicate 550 12E1Sit1 of Cylindrotheca fusiformis
2.A.33NhaA Na+:H+350-400(12)2B1Na+:H+ antiporter NhaA of Escherichia coli
2.A.34NhaB Na+:H+c. 5209B1Na+:H+ antiporter NhaB of Escherichia coli
2.A.35NhaC Na+:H+c. 46012B1Na+:H+ antiporter NhaC of Bacillus firmus
2.A.36CPA1 Na+:H+; Na+ or K+:H+400-90010-12A, B, ENa+:H+ antiporter Nhe-1 of Rattus norvegicus
2.A.37CPA2 Na+:H+ or K+:H+250-650 + 150-300 10-14A, B, E2K+ efflux protein-C KefC of Escherichia coli
2.A.38Trk K+400-600 8A, B, E2K+ uptake permease TrkH of Escherichia coli
2.A.39NCS1 nucleobases; thiamin; nucleosides400-650 12A, B, E2cytosine permease CodB of Escherichia coli
2.A.40NCS2 nucleobases; urate 400-600 12A, B, E2uracil permease UraA of Escherichia coli
2.A.41CNT nucleosides 350-700 10; 13A, B, E2nucleoside,H+ symporter NupC of Escherichia coli
2.A.42HAAAP hydroxy and aromatic amino acids400-450 11B2tyrosine permease TyrP of Escherichia coli
2.A.43LCT cystine 200-400 7E2lysosomal cystine transporter, cystinosin, of Homo sapiens
2.A.44FNT formate; nitrite 250-650 6 (6-8)A, B, E2formate efflux permease FocA of Escherichia coli
2.A.45ArsB arsenite, antimonite 400-900 12A, B, E2arsenical resistance efflux pump of Staphylococcus aureus
2.A.46BenE benzoate c. 40012B1benzoate,H+ symporter BenE of Acinetobacter caleoaceticus
2.A.47DASS di- and tricarboxylates; phosphate; sulfate400-950 11-14A, B, E2dicarboxylate translocator SodiT1 of Spinacia oleracea
2.A.48RFC reduced folate; TPP; thiamin 500-600 12E (An)2reduced folate carrier RFC of Mus musculus
2.A.49Amt ammonium 350-650 11; 12A, B, E2ammonium transporter AmtB of Escherichia coli
2.A.50GUP glycerol 450-650 8-10B, E1GUP1 of Saccharomyces cerevisiae
2.A.51CHR chromate; sulfate (uptake or efflux)c. 4006; 10A, B2the chromate transporter ChrA of Alcaligenes eutrophus
2.A.52NiCoT Ni2+, Co2+; Ni2+300-400 8B2Ni2+ uptake permease HoxN of Ralstonia eutropha
2.A.53SulP sulfate; sulfate, bicarbonate; anions400-900 10-13A, B, Esulfate porter or permease SulP of Homo sapiens
2.A.54MTC di- and tricarboxylates c. 2905-6E (Mito)1mitochondrial tricarboxylate carrier MTC of Rattus norvegicus
2.A.55Nramp divalent metal ions (uptake)500-600 8-12A, B, E2divalent metal ion,H+ symporter Nramp2 of Homo sapiens
2.A.56TRAP-T C4-dicarboxylates; acidic amino acids; sugars (?) c. 1000 (three components)12+4+0A, B2dicarboxylate transporter DctPQM of Rhodobacter capsulatus
2.A.57ENT nucleosides c. 450 10-11E2equilibrative nucleoside transporter-1 hENT1 of Homo sapiens
2.A.58PNaS inorganic phosphate300-650 8B, E2renal Na+-dependent phosphate transporter-2 NPT2 of Rattus norvegicus
2.A.59ACR3 arsenite c. 40010A, B, E1arsenical resistance-3 protein ACR3 of Saccharomyces cerevisiae
2.A.60OAT organic anions; prostaglandins; bile acids; bile conjugates; drugs;hormones600-700 10-12E (An)2organic anion transporter OATP1 of Rattus norvegicus; prostaglandin transporter PGT of Rattus norvegicus
2.A.61DcuC dicarboxylates c. 46010-12B0C4-dicarboxylate uptake porter DcuC of Escherichia coli
2.A.62NhaD Na+:H+400-450 10-12A, B1Na+:H+ antiporter NhaD of Vibrio parahaemolyticus
2.A.63CPA3 K+ or Na+:H+>700; possibly multiple componentsc. 17B1K+:H+ antiporter PhaA-G of Rhizobium meliloti; Na+:H+ antiporter Nha1 of an alkalophilic Bacillus species
2.A.64Tat proteins, mostly redox proteins >600 (2-4 subunits)9 (6+1+1+1)A, B, E2twin arginine targeting and translocation TatABCE system of Escherichia coli
2.A.65BRT bilirubin c. 3505E (An)0bilirubin transporter of Rattus norvegicus
2.A.66MATE drugs, dyes; nucleotides?400-700 12A, B, E3norfloxacin and other drug efflux pump NorM of Vibrio parahaemolyticus
2.A.67OPT peptides 600-900 12-15A, B, E2oligopeptide transporter OPT1 of Candida albicans
2.A.68AbgT aminobenzoyl- glutamate c. 50012-13B1aminobenzoylglutamate transporter AbgT of Escherichia coli
2.A.69AEC auxin (efflux)600-700 8-2A, B, E2auxin efflux carrier PIN1 of Arabidopsis thaliana
2.A.70MSS malonate 255+1297+4B0malonate,Na+ symporter MadLM of Malonomonas rubra
2.A.71FBT folate, biopterin, methotrexate 450-650 12B, E1folate/biopterin transporter of Leishmania donovani
2.A.72KUP K+ (uptake) 400-800 12B, E2K+,H+ symporter Hak1 of Neurospora crassa
2.A.73ICT HCO3-350-500 10B1HCO3-,Na+ symporter of Synechococcus PCC7942
2.A.74MET thymidine, drugs, steroids200-300 4E (An)1lysosomal hydrophobe/amphiphile transporter MTP of Mus musculus
2.A.75LysE basic amino acids150-250 5B1lysine/arginine exporter LysE of Corynebacterium glutamicum
2.A.76RhtB neutral amino acids and their derivatives150-250 5B2neutral amino acid exporter RhtB of Escherichia coli
2.A.77CadD Cd2+; cations 150-250 5B1cadmium resistance protein CadD of Staphylococcus aureus
2.A.78LIV-ELeu, Ile, Valc. 250 + c. 1107+4A, B, E(Pr)2AzlC, AzlD of Bacillus subtilis
2.A.79ThrE Thr, Ser450-600 10A, B, E2Thr/Ser:H+ antiporter of Corynebacterium glutamicum
2.A.80Tct tricarboxylates c. 50012+4+0B,(A?)TctABC of Salmonella enterica

2.B Non-ribosomally synthesized transporters

These substances, like the non-ribosomally synthesized channels, may be depsipeptides or non-peptidic substances. These transporters complex a solute (often a cation) in their hydrophilic interior and facilitate translocation of the complex across the membrane by exposing their hydrophobic interior and moving from one side of the bilayer to the other. If the free transporter can cross the membrane in the noncomplexed form, the transport process is electrophoretic (the charged molecule moves down its electrochemical gradient) but if the complex crosses the membrane, transport may be electroneutral because one charged substrate is exchanged for another. Strictly speaking, this subclass does not comprise any proteins but it is included here for the sake of classifying all transmembrane movement facilitators.

TC no. a Family Substrates b Size range c Distributione nf Examples
2.B.1Valinomycin K+6 amino acids plus 6 organic acidsB0valinomycin of Streptomyces fuvlissimus
2.B.2Monensin K+, Na+, H+no amino acidsB0monensin A of Streptomyces cinnamonensi
2.B.3Nigericin K+, H+no amino acidsB0grisorixin of Streptomyces griseus
2.B.4MA univalent cations no amino acidsB1nonactin of Streptomyces griseus
2.B.5MP cations no amino acidsB2macrocyclic polyethers (crown compounds)
2.B.6Ionomycin divalent cations no amino acidsB0ionomycin of Streptomyces conglobatus

a Number of the family according to the transport protein classification system.

b Substrates of single transporters within a family are separated by commas; substrates transported by different protein members of the family are separated by semicolons. When various solutes serve as transported substrates, they are separated by a slash; when two different solutes are transported in a symport fashion, they are separated by a comma; when two or more substrates are transported in an antiport fashion they are separated by a colon.

c Size range (in number of amino acid residues) when a single type of subunit is present, or for the entire complex when several types of subunits are present. In some cases the individual subunits in multisubunit systems are indicated separately.

d Number of (putative) transmembrane a-helical segments, TMS, (or b-strands in section 1.B) in a polypeptide chain. Underlined numbers indicate that the number is established by X-ray chrystallographic data or that substantial experimental evidence suggests the proposed topology, usually as a result of the use of gene fusion technology. If not underlined, numbers indicate the number of TMS predicted on the basis of hydropathy analysis using available programs such as WHAT and AveHAS see the Web site at ( In some cases, the numbers of predicted TMS is zero, and hence a "0" is entered. In many such cases, the actual TMS is (are) amphipathic, and hence the program does not predict the number correctly. Subscripts refer to the number of polypeptide chains in the complex when known; n indicates an oligomeric structure of unknown or poorly defined number of subunits. If alternative structures are found for different transporters within a single family, these are separated by semicolons.

e Abbreviations used for types of organisms, organelles and viruses are as follows: B, Bacteria; A, Archaea; E, Eucarya; G-, Gram-negative bacteria; G+, Gram-positive bacteria; Y, yeasts; Fu, fungi; Pr, protozoans; Pl, plants; An, animals; Mito, mitochondria; Chloro, chloroplasts; ER, endoplasmic reticulum; Bp, bacteriophage; V, virus

f The numbers represent the order of magnitude of members in this family as of November 2001. 0: between 1 and 5; 1: between 6 and 49; 2: between 50 and 499; 3: more than 500.

g D-erythro-3-Deoxyhexulosonate was formerly called 2-keto-3-deoxygluconate hence the family name KDGT; it may also be described as 2-dehydro-3-deoxy-D-gluconate.

Continued with Properties of Family 3
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