Classification of Membrane Transport Proteins

Continued from properties of families 2

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

3. Primary Active Transporters

3.A P-P-bond-hydrolysis-driven transporters

This subclass includes transport systems that use the free energy of P-P bond hydrolysis to drive the movement of substances against their chemical or electrochemical potential gradient. The transport protein may be transiently phosphorylated during the transport cycle (the 3.A.3 and 3.A.4 groups) but the substrate itself is not phosphorylated. These transporters occur universally in all domains of life.

TC no. a Family Substrates b Size range c Number of transmembrane segmentsd Distributione nf Examples
3.A.1ABCall kinds of inorganic and organic molecules of small, intermediate and large sizes, from simple ions to macromolecules1000-2000 (multidomain; usually multisubunit)(5)2; (6)2; 12 variableA, B, E3maltose transporter MalEFGK of Escherichia coli; multidrug resistance protein MDR of Homo sapiens
3.A.2F-ATPaseH+; Na+>4000 (multiple subunits)(2)10 + (1)2 +(5)1A, B, E (chloro; mito)2FoF1-ATPase of human Mito
3.A.3P-ATPasecations (uptake and/or efflux):Na+: K+; H+: K+; Ca2+/ K+; Na+; H+; K+; Ca2+; Ca2+/Mn2+; Mg2+; Mn2+; Cu2+; Cu+/Ag+; Ag+; Zn2+/ Cd2+/ Co2+/Ni2+/Pb2+; Cl (some systems may be specific for one or only a few of these heavy metal cations); phospholipids (flipping)600-1200 (sometimes multisubunit)(6-12), 8, 10A, B, E3KdpABC (K+ uptake) of Escherichia coli
3.A.4ArsABarsenite, antimonite, (tellurite?)c. 1100 (multidomain; two subunits)12A, B, E2arsenite efflux pump ArsAB of Escherichia coli
3.A.5IISPproteins>2000 (multiple subunits)SecY (10) SecE 1SecG 1 or 2A, B, Etype II secretory pathway system SecAYEG of Escherichia coli
3.A.6IIISPproteins>2000 (multiple subunits)>10 integral membrane constituentsB2type III secretory pathway system YscNDRSTUC; LcrD of Yersinia species
3.A.7IVSPproteins, protein-DNA complexes>2000 (multiple subunits)>10 integral membrane constituentsB2type IV secretory pathway system VirB2-11 of Agrobacterium tumefaciens
3.A.8MPTMitol proteins>2000 (multiple subunits)>9 integral membrane constituentsE (Mito)1Mitol transport protein complex Tom and Tim of Saccharomyces cerevisiae
3.A.9CEPTchloroplast proteins>2000 (multiple subunits)several integral membrane constituentsE (Chloro)1chloroplast transport protein complex IAP of Pisum sativum
3.A.10H+-PPaseH+650-80015B, E (Pl vacuoles)2vacuolar H+-diphosphatase of Arabidopsis thaliana
3.A.11DNA-Tsingle-stranded DNA>1000 (multiple subunits)3 subunitsB1competence-related DNA transformation transporter ComEA-EC-FA of Bacillus subtilis
3.A.12S-DNA-TDNA, DNA-protein complexes600-13502, 4, 6B2cell division protein FtsK of Escherichia coli
3.A.13FPhEviruses109 + 348 + 4761Bp1filamentous phage assembly/export channel
3.A.14FPEproteins320-420 + 350-570 3B1competence-related pilin exporter of Bacillus subtilis

3.B Decarboxylation-driven transporters

Systems that drive ion transport at the expense of free energy of decarboxylation of a cytoplasmic substrate are included here. Only prokaryotic cells are known to harbor such systems.

TC no. a Family Substrates b Size range c Number of transmembrane segmentsd Distributione nf Examples
3.B.1NaT-DCNa+c. 1000
(4 subunits)
10A, B 2oxaloacetate decarboxylase of Salmonella typhimurium

3.C Methyl-transfer-driven transporters

This subclass currently contains a single family; probably only in Archaea.

TC no. a Family Substrates b Size range c Number of transmembrane segmentsd Distributione nf Examples
3.C.1NaT-MMMNa+c. 8 subunits; most integral membrane constituents6-7(A), 1(B), 8(C), 2-7(D), 0-2(E), 1(F), 1(G), 1(H)A1Na+-transporting methyltetrahydro-methanopterin: coenzyme M methyl-transferase of Methanobacterium thermoautotrophicum

3.D Oxidoreduction-driven transporters

This subclass contains systems where the transport of a solute is driven by the free energy of oxidation of a reduced substrate transmitted by the flow of electrons. Transporters of this type are universal although some families are restricted to one or another domain of life.

TC no. a Family Substrates b Size range c Number of transmembrane segmentsd Distributione nf Examples
3.D.1NDHNa+; H+ (efflux)14-40 subunitsmultiple integral membrane subunitsB, E (Mito, Chloro)2NDH of Escherichia coli
3.D.2PTHH+ (efflux)c. 2000 (13 proteins; 3 domains; dimeric)(12-14)2B, E (Mito)2PTH of Escherichia coli
3.D.3QCRH+ (efflux)2000-6000 multiple (3-11) subunits; dimeric8 (C), 1 (D), 1(G), 1(J), 1(K)B, E (Mito; chloro)cytochrome bc1 complex of Bos taurus
3.D.4COXH+ (efflux)2000-6000 multiple (3-11) subunits; dimericE: 12 (I), 2 (II), 7 (III), 1 (IV), 1 (VIa), 1 (VIc), 1(VIIa), 1(VIIb), 1 (VIIc), 1 (VIII) B: 12 (I), 2(II)A, B, E, (Mito)3cytochrome c oxidase of Bos taurus
3.D.5Na-NDHNa+ (efflux)multiple subunits9(B); 1(C): 5(D); 6(E); 3(F)B1Na+-translocating NADH-quinol reductase of Vibrio alginolyticus
3.D.6NFOH+ or Na+ (efflux)multiple subunits5 + 1 + 6 + 1 + 24 + 9B1H+- or Na+- translocating NADH:ferredoxin oxidoreductase,rnfA-H of Rhodobacter capsulatus
3.D.7HHOH+ (efflux)multiple subunits2(D); 6(E);4(G); 1(A); 5(C)A, B1H2:heterodisulfide oxidoreductase of Methanosarcina mazei
3.D.8FMF-DHH+ or Na+ (efflux)multiple subunits2(F); 1(G)A1formyl methanofuran dehydrogenase Fwd A-G of Methanobacterium thermoautotrophicum
3.D.9F420H2DHreduced donor, H+Mr of complex about 1201(F); 14(N); 14(M); 19(L); 2(K); 5(J); 1(I); 7(H); 3(A)A1 F420H2DH of Methanosarcina mazei

3.E Light-driven transporters

A single family of archebacterial proteins is involved in light-driven transport. However, homologous retinal-binding proteins have been found in fungi where they behave as heat-shock proteins and possibly as molecular chaperones. The light-driven reduction of the photosynthetic reaction center is only auxiliary to subsequent oxidation in the cytochrome b6f complex where the efflux of hydrons actually takes place.

TC no. a Family Substrates b Size range c Number of transmembrane segmentsd Distributione nf Examples
3.E.1MRH+ (efflux); Cl (uptake)c. 2507A, E(Fu)2bacteriorhodopsin of Halobacterium salinarum
3.E.2PRCH+ (efflux)multiple subunits5+5+1B, E (Chloro)2reaction center and cytochrome b6f complex of Rhodobacter sphaeroides

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.

Continued with Properties of Family 4
Return to Membrane Transport Proteins home page
Return to Biochemical Nomenclature home page