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

2. Electrochemical-Potential-Driven Transporters

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.1	MFS	numerous small molecules (also can serve as receptors)	300-1250	6, 12 or 14	A, B, E	3	lactose transporter or permease LacY of Escherichia coli; drug efflux transporter or permease EmrD of Escherichia coli
2.A.2	GPH	sugars (glycosides)	250-650	1	A, B, E	2	melibiose transporter or permease MelB of Escherichia coli
2.A.3	APC	amino acids, polyamines, organic cations (also can serve as receptors)	400-1250	10, 12, 14	A, B, E	2	lysine transporter or permease LysP of Escherichia coli
2.A.4	CDF	Cd2+, Co2+, Ni2+	300-750	6	A, B, E	2	heavy metal uptake and efflux transporters of bacteria, eukaryotic plasma membranes and mitochondria (CzcD of Ralstonia eutropha)
2.A.5	ZIP	Zn2+; Fe2+	376	8	E	2	zinc uptake transporter Zrt1 of Saccharomyces cerevisiae
2.A.6	RND	heavy metal ions; multiple drugs; oligosaccharides; organic solvents, fatty acids; phospholipids, cholesterol	800-1200	6, 12	A, B, E	3	drug efflux pump AcrA of Escherichia coli
2.A.7	DMT	multiple drugs; sugars and derivatives; nucleotides, nucleotide sugars	100-500	(4)2, (5)2, 10	B	3	cationic drug efflux pump Smr of Staphylococcus aureus
2.A.8	GntP	gluconate, idonate	400-500	c. 12-14	B	2	gluconate permease GntP of Bacillus subtilis
2.A.9	Oxa1	proteins	350-450	5	B, E	1	Oxalp of Saccharomyces cerevisiae
2.A.10	KDGT	D-erythro-3-deoxyhexulosonate g	300-400	10-12	B	1	2-keto-3-deoxygluconate transporter KdgT of Erwinia chrysanthemi
2.A.11	CitMHS	citrate-M2+	400-450	12	B	1	citrate,Me2+/H+ symporter CitM of Bacillus subtilis
2.A.12	AAA	ATP, ADP	450-650	12	B, E(Pl)	1	ATP/ADP exchange translocator of Rickettsia prowazekii
2.A.13	Dcu	C4-dicarboxylates	440	10, 12	B(G-)	1	dicarboxylate uptake porter-A DcuA of Escherichia coli
2.A.14	LctP	lactate	450-600	12	A, B	1	lactate transporter LctP of Escherichia coli
2.A.15	BCCT	glycine; betaine; carnitine; choline; multiple organic cations	450-700	12	B	2	carnitine transporter CaiT of Escherichia coli
2.A.16	TDT	tellurite; dicarboxylates	300-350	10	A, B, E	1	tellurite uptake transporter TehA of Escherichia coli
2.A.17	POT	peptides; nitrates; amino acids	450-800	12	B, E	2	dipeptide transporter DtpT of Lactococcus lactis
2.A.18	AAAP	amino acids and their derivatives	400-750	11	E	2	amino acid/auxin,H+ symporter Aux-1 of Arabidopsis thaliana
2.A.19	CaCA	Ca2+	350-400	10 or 11	A, B, E	2	Ca2+:H+ antiporter ChaA of Escherichia coli
2.A.20	PiT	inorganic phosphate; sulfate	400-700	10-12	A, B, E	2	phosphate transporter PitA of Escherichia coli
2.A.21	SSS	sugars; amino acids; vitamins; nucleosides; inositols; iodide, organic and inorganic anions; urea; organic cations (also can serve as receptors)	400-750	12-15	A, B, E	2	pantothenate,Na+ symporter PanF of Escherichia coli
2.A.22	NSS	neurotransmitters (often amino acids); osmolytes; taurine; creatine	600-750	12	A, B, E (An)	3	serotonin,Na+ symporter of Homo sapiens
2.A.23	DAACS	C4-dicarboxylates; acidic and neutral amino acids	400-600	8-10	A, B, E	2	glutamate/aspartate porter GltP of Escherichia coli
2.A.24	CCS	mono-, di- and tricarboxylates	400-450	12	B	1	citrate,Na+ symporter CitS of Klebsiella pneumoniae
2.A.25	AGCS	alanine, glycine	400-550	8-12	B	2	alanine/glycine transporter DagA of Alteromonas haloplanktis
2.A.26	LIVCS	branched-chain amino acids, Leu, Ile, Val	400-450	12	B	1	branched-chain amino acid transporter BraB of Pseudomonas aeruginosa
2.A.27	ESS	glutamate	c. 400	10	B	1	glutamate,Na+ symporter GltS of Escherichia coli
2.A.28	BASS	bile acids	350-500	7	B, E (An)	1	bile acid uptake system of Rattus norvegicus
2.A.29	MC	ATP/ADP/AMP; Pi; organic anions; H+; carnitine/acyl carnitine; basic amino acids; FAD	300-750	6	E (Mito)	3	ADP/ATP exchanger of Homo sapiens in mitochondria and peroxisomes
2.A.30	CCC	K+, Na+, Cl-; KCl; NaCl	1000-1200	12	A, B, E	2	NaCl,KCl cotransporter of Rattus norvegicus
2.A.31	AE	inorganic anions	900-1250	14	E	2	anion exchanger AE1 of Homo sapiens
2.A.32	Sit	silicate	550	12	E	1	Sit1 of Cylindrotheca fusiformis
2.A.33	NhaA	Na+:H+	350-400	(12)2	B	1	Na+:H+ antiporter NhaA of Escherichia coli
2.A.34	NhaB	Na+:H+	c. 520	9	B	1	Na+:H+ antiporter NhaB of Escherichia coli
2.A.35	NhaC	Na+:H+	c. 460	12	B	1	Na+:H+ antiporter NhaC of Bacillus firmus
2.A.36	CPA1	Na+:H+; Na+ or K+:H+	400-900	10-12	A, B, E		Na+:H+ antiporter Nhe-1 of Rattus norvegicus
2.A.37	CPA2	Na+:H+ or K+:H+	250-650 + 150-300	10-14	A, B, E	2	K+ efflux protein-C KefC of Escherichia coli
2.A.38	Trk	K+	400-600	8	A, B, E	2	K+ uptake permease TrkH of Escherichia coli
2.A.39	NCS1	nucleobases; thiamin; nucleosides	400-650	12	A, B, E	2	cytosine permease CodB of Escherichia coli
2.A.40	NCS2	nucleobases; urate	400-600	12	A, B, E	2	uracil permease UraA of Escherichia coli
2.A.41	CNT	nucleosides	350-700	10; 13	A, B, E	2	nucleoside,H+ symporter NupC of Escherichia coli
2.A.42	HAAAP	hydroxy and aromatic amino acids	400-450	11	B	2	tyrosine permease TyrP of Escherichia coli
2.A.43	LCT	cystine	200-400	7	E	2	lysosomal cystine transporter, cystinosin, of Homo sapiens
2.A.44	FNT	formate; nitrite	250-650	6 (6-8)	A, B, E	2	formate efflux permease FocA of Escherichia coli
2.A.45	ArsB	arsenite, antimonite	400-900	12	A, B, E	2	arsenical resistance efflux pump of Staphylococcus aureus
2.A.46	BenE	benzoate	c. 400	12	B	1	benzoate,H+ symporter BenE of Acinetobacter caleoaceticus
2.A.47	DASS	di- and tricarboxylates; phosphate; sulfate	400-950	11-14	A, B, E	2	dicarboxylate translocator SodiT1 of Spinacia oleracea
2.A.48	RFC	reduced folate; TPP; thiamin	500-600	12	E (An)	2	reduced folate carrier RFC of Mus musculus
2.A.49	Amt	ammonium	350-650	11; 12	A, B, E	2	ammonium transporter AmtB of Escherichia coli
2.A.50	GUP	glycerol	450-650	8-10	B, E	1	GUP1 of Saccharomyces cerevisiae
2.A.51	CHR	chromate; sulfate (uptake or efflux)	c. 400	6; 10	A, B	2	the chromate transporter ChrA of Alcaligenes eutrophus
2.A.52	NiCoT	Ni2+, Co2+; Ni2+	300-400	8	B	2	Ni2+ uptake permease HoxN of Ralstonia eutropha
2.A.53	SulP	sulfate; sulfate, bicarbonate; anions	400-900	10-13	A, B, E		sulfate porter or permease SulP of Homo sapiens
2.A.54	MTC	di- and tricarboxylates	c. 290	5-6	E (Mito)	1	mitochondrial tricarboxylate carrier MTC of Rattus norvegicus
2.A.55	Nramp	divalent metal ions (uptake)	500-600	8-12	A, B, E	2	divalent metal ion,H+ symporter Nramp2 of Homo sapiens
2.A.56	TRAP-T	C4-dicarboxylates; acidic amino acids; sugars (?)	c. 1000 (three components)	12+4+0	A, B	2	dicarboxylate transporter DctPQM of Rhodobacter capsulatus
2.A.57	ENT	nucleosides	c. 450	10-11	E	2	equilibrative nucleoside transporter-1 hENT1 of Homo sapiens
2.A.58	PNaS	inorganic phosphate	300-650	8	B, E	2	renal Na+-dependent phosphate transporter-2 NPT2 of Rattus norvegicus
2.A.59	ACR3	arsenite	c. 400	10	A, B, E	1	arsenical resistance-3 protein ACR3 of Saccharomyces cerevisiae
2.A.60	OAT	organic anions; prostaglandins; bile acids; bile conjugates; drugs;hormones	600-700	10-12	E (An)	2	organic anion transporter OATP1 of Rattus norvegicus; prostaglandin transporter PGT of Rattus norvegicus
2.A.61	DcuC	dicarboxylates	c. 460	10-12	B	0	C4-dicarboxylate uptake porter DcuC of Escherichia coli
2.A.62	NhaD	Na+:H+	400-450	10-12	A, B	1	Na+:H+ antiporter NhaD of Vibrio parahaemolyticus
2.A.63	CPA3	K+ or Na+:H+	>700; possibly multiple components	c. 17	B	1	K+:H+ antiporter PhaA-G of Rhizobium meliloti; Na+:H+ antiporter Nha1 of an alkalophilic Bacillus species
2.A.64	Tat	proteins, mostly redox proteins	>600 (2-4 subunits)	9 (6+1+1+1)	A, B, E	2	twin arginine targeting and translocation TatABCE system of Escherichia coli
2.A.65	BRT	bilirubin	c. 350	5	E (An)	0	bilirubin transporter of Rattus norvegicus
2.A.66	MATE	drugs, dyes; nucleotides?	400-700	12	A, B, E	3	norfloxacin and other drug efflux pump NorM of Vibrio parahaemolyticus
2.A.67	OPT	peptides	600-900	12-15	A, B, E	2	oligopeptide transporter OPT1 of Candida albicans
2.A.68	AbgT	aminobenzoyl- glutamate	c. 500	12-13	B	1	aminobenzoylglutamate transporter AbgT of Escherichia coli
2.A.69	AEC	auxin (efflux)	600-700	8-2	A, B, E	2	auxin efflux carrier PIN1 of Arabidopsis thaliana
2.A.70	MSS	malonate	255+129	7+4	B	0	malonate,Na+ symporter MadLM of Malonomonas rubra
2.A.71	FBT	folate, biopterin, methotrexate	450-650	12	B, E	1	folate/biopterin transporter of Leishmania donovani
2.A.72	KUP	K+ (uptake)	400-800	12	B, E	2	K+,H+ symporter Hak1 of Neurospora crassa
2.A.73	ICT	HCO3-	350-500	10	B	1	HCO3-,Na+ symporter of Synechococcus PCC7942
2.A.74	MET	thymidine, drugs, steroids	200-300	4	E (An)	1	lysosomal hydrophobe/amphiphile transporter MTP of Mus musculus
2.A.75	LysE	basic amino acids	150-250	5	B	1	lysine/arginine exporter LysE of Corynebacterium glutamicum
2.A.76	RhtB	neutral amino acids and their derivatives	150-250	5	B	2	neutral amino acid exporter RhtB of Escherichia coli
2.A.77	CadD	Cd2+; cations	150-250	5	B	1	cadmium resistance protein CadD of Staphylococcus aureus
2.A.78	LIV-E	Leu, Ile, Val	c. 250 + c. 110	7+4	A, B, E(Pr)	2	AzlC, AzlD of Bacillus subtilis
2.A.79	ThrE	Thr, Ser	450-600	10	A, B, E	2	Thr/Ser:H+ antiporter of Corynebacterium glutamicum
2.A.80	Tct	tricarboxylates	c. 500	12+4+0	B,(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.1	Valinomycin	K+	6 amino acids plus 6 organic acids	B	0	valinomycin of Streptomyces fuvlissimus
2.B.2	Monensin	K+, Na+, H+	no amino acids	B	0	monensin A of Streptomyces cinnamonensi
2.B.3	Nigericin	K+, H+	no amino acids	B	0	grisorixin of Streptomyces griseus
2.B.4	MA	univalent cations	no amino acids	B	1	nonactin of Streptomyces griseus
2.B.5	MP	cations	no amino acids	B	2	macrocyclic polyethers (crown compounds)
2.B.6	Ionomycin	divalent cations	no amino acids	B	0	ionomycin of Streptomyces conglobatus

^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 (http://www.biology.ucsd.edu/~yzhai/biotools.html). 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.