Classification of Membrane Transport Proteins

Continued from families 4 to 9

Properties of Families of Transport Proteins Included in the TC System

1. Pores and channels

1.A a-Helical channels

Transmembrane channel proteins of this subclass are ubiquitously found in the membranes of all types of organisms, from bacteria to higher eukaryotes. These transporters usually catalyze the movement of solutes by an energy-independent passage through a trans-membrane aqueous pore without evidence for a porter (i.e. carrier)-mediated mechanism. These channel proteins consist largely of a-helical transmembrane segments even if some b-form secondary structure may be present even in the transmembrane channel itself.

TC no. a Family Substrates b Size range c Number of transmembrane segmentsd Distributione nf Examples
1.A.1VICNa+; K+; Ca2+; multiple cationswidely varied (2)4;(4)2; (6)4; (8)2;(12)2; (24)1; often heterooligomericA, B, E3voltage-gated Na+ channels; voltage-gated Ca2+ channels; K+ channels sensitive to voltage, Ca2+ or cyclic nucleotides of Homo sapiens
1.A.2IRK-CK+350-500(2)4E (An)2inward rectifier K+ channels (ATP-activated or G-protein regulated) of Homo sapiens
1.A.3RIR-CaCCa2+5000 or 2500(6)4E (An)2ryanodine receptor Ca2+ channels; inositol-1,4,5-trisphosphate receptor Ca2+ channels of Homo sapiens
1.A.4TRP-CCCa2+, other cations800-1500(6)4E (An)3transient receptor potential Ca2+channel, TRP of Drosophila melanogaster
1.A.5PCCNa+, K+, Ca2+4000(7-11)n (6)mE (An)1polycystins 1 and 2 of Homo sapiens
1.A.6ENaCNa+; cations600-700(2)4 (a2bg)E (An)2epithelial Na+ channels; degenerins; heterooligomeric peptide-gated ionotropic receptors of animals
1.A.7ACCunivalent cations, Ca2+350-600(2)nE (An)2ATP-gated cation channel P2X1 of Homo sapiens
1.A.8MIPH2O; H2O, urea; cations; anions; glycerol, polyols80-700(6)4A, B, E3aquaporins, Aqp1 of Homo sapiens; glycerol facilitators, GlpF, of Escherichia coli
1.A.9LICcations or anions400-700(3-5)5; often heterooligomericE (An)3acetylcholine- or serotonin-activated cation channels; glycine, glutamate or GABA-regulated Cl channels of Homo sapiens
1.A.10GICunivalent cations and Ca2+250-1500(3 or 5)5B, E (An)2glutamate-regulated ionotropic channels of Rattus norvegicus
1.A.11ClCCl-, anions400-100012A, B, E2voltage-gated Cl channel, ClC1 of Homo sapiens
1.A.12O-ClCCl-, anions250-450(2)nE (An)2organellar voltage-sensitive Cl- channels of Bos taurus
1.A.13E-ClCCl-, anions900 (4)nB, E (An)1Ca2+-activated Cl channel-2 of Homo sapiens
1.A.14NSCC1Na+, Li+, K+c. 450(4)nE (An)0nonselective cation channel, NSC1 of Mus musculus
1.A.15NSCC2Na+, K+, Cs+; slowly Ca2+250-400(2)nE (An, F)1nonspecific channel translocationprotein-1 NS1, of Homo sapiens; Sec62 of Saccharomyces cerevisiae
1.A.16Mid1Ca2+450-5501 or 2E (Y)1Mid1 of Saccharomyces cerevisiae
1.A.17CSCions, solutes150-200b-structure?E (Pl)1chloroplast outer envelope solute channel, CSC of Pisum sativum
1.A.18Tic110anions, proteins10002E (Pl)1protein-import-related anion-selective channel, Tic110 of Pisum sativum
1.A.19M2-CH+c. 100(1)4V0matrix protein, M2 of influenza virus
1.A.20CybBH+450-7506 heterooligomericE (An, Pl)2gp91phox phagocyte NADPH oxidase-associated cytochrome b558 H+ channel of Homo sapiens
1.A.21Bcl-2protein (cyt c)100-350(1-5)n (n=2?)E (An), V2apoptosis regulator, Bcl-X(L) of Homo sapiens
1.A.22MscLproteins, ions (slightly cation- selective)100-200(2)5B1large mechanosensitive ion channels, MscL of E.coli
1.A.23MscSions (slightly anion-selective)200-11503-14A, B, E2small-conductance mechanosensitiveion channel, KefA of Escherichia coli
1.A.24Connexin smallmolecules(no discrimination)200-600(4)nE (An)2vertebrate connexin 43 (gap junction-1 protein) of Rattus norvegicus
1.A.25Innexinsmallmolecules(no discrimination)300-600(4)nE (An)2invertebrate innexin UNC-7 of Caenorhabditis elegans
1.A.26PPDsmall moleculesc. 3001E(Pl)1gap junction protein CX32 of Arabidopsis thaliana
1.A.27PLMCl- (anion-selective), taurine, lactate, glutamate, isethionate, gluconate 80-100(1)nE (An)1phospholemman; Cl- conductance inducer protein Mat-8 of Mus musculus
1.A.28UTurea, water350-40010E (An)1kidney vasopressin-regulated urea transporter UT2 of Rattus norvegicus
1.A.29UACurea, amides150-250 6B1UreI protein of Helicobacter pylori
 1.A.30.1MotH+; Na+ 200-350 (MotA)200-500 (MotB)41B2MotA and MotB proteins of Escherichia coli
 1.A.30.2 ExbH+ (energy-transducing system)150-400+150- 350+100-200 (TonB ExbBD) 350-450+200- 300+100-200 (TolAQR)1+3+1


B(G-)2TonB/ExbB/ExbD of Escherichia coli
1.A.31Annexin ions250-7004, 8E2Hydra annexin XII
1.A.32NB-Cions c. 1001V0NB protein of influenza B virus
1.A.33Hsp70ions, polypeptides500-750 0-2A,B,E3Hsp70 protein of Arabidopsis thaliana
1.A.34EVE1-CRNA1200-13005V1herpes simplex structural polyprotein
1.A.35MIT heavy metal ions300-4002-3B2CorA protein of Escherichia coli
1.A.36ICCanions500-6004E0MCLC protein of Homo sapiens

1.B b-Strand porins

These proteins form transmembrane pores that usually allow the energy-independent passage of solutes across a membrane. The transmembrane portions of these proteins consist exclusively of b-strands that usually form b-barrels. Porins are found in the outer membranes of Gram-negative bacteria, mitochondria, chloroplasts and possibly of acid-fast Gram-positive bacteria.

TC no. a Family Substrates b Size range c Number of transmembrane segmentsd Distributione nf Examples
1.B.1GBPions, small molecules250-45016-stranded antiparallel b-barrelsB(G-),V2OmpF of Escherichia coli
1.B.2CPions, small molecules300-400B1Omp1 of Chlamydia psittaci
1.B.3SPsugars250-55018-stranded antiparallel b-barrelsB1LamB of Escherichia coli
1.B.4BRPions, small molecules300-400B1Omp2 of Brucella abortus
1.B.5POPions, small molecules400-450B1OprP of Pseudomonas aeruginosa
1.B.6OOPions, small molecules350-4508 b-strandsB2OmpA of Escherichia coli
1.B.7RPPions, small molecules250-35016-stranded b-barrelsB0PorCa porin of Rhodobacter capsulatus
1.B.8MPPanions, small proteins250-3501 a-helix and 12 or 13 b-strandsE2E2 mitochondrial outer membrane VDAC of Saccharomyces cerevisiae
1.B.9FadLfatty acids400-500B1FadL of Escherichia coli
1.B.10Tsxnucleosides250-30014-stranded b-barrelsB1Tsx of Escherichia coli
1.B.11FUPfimbrial protein750-95024 b-strandsB2FacD of Escherichia coli
1.B.12ATN-terminal protein domains250-30014 b-strandsB(G-)2AidA of Escherichia coli
1.B.13AEPalginate c. 50018 b-strandsB(G-)0AlgE of Pseudomonas aeruginosa
1.B.14OMRiron-chelate complexes, colicins, vitamin B12, etc.350-110022 antiparallel b-strandsB(G-)2FepA of Escherichia coli
1.B.15RafYsmall molecules, oligosaccharides450-500B(G-)1RafY of Escherichia coli
1.B.16SAPshort-chain amides, small moleculesc. 400B(G-)FmdC of Methylophilus methylotrophus
1.B.17OMFproteins; lipooligosaccharides; drugs, dyes, signaling molecules; heavy-metal ions; etc. (some OMFs can accommodate multiple substrate types)400-550(4)3 -strandsB(G-)2TolC of Escherichia coli
1.B.18OMAcomplex carbohydrates350-600B(G-)2ExoF of Rhizobium meliloti
1.B.19OprBions; small molecules400-500B(G-)1OprB of Pseudomonas aeruginosa
1.B.20TPSproteins550-600B(G-)2ShlB of Serratia marcescens
1.B.21OmpGions, small moleculesc. 30016B(G-)OmpG of Escherichia coli
1.B.22Secretinproteins400-800(x)12B, VPulD of Klebsiella oxytoca
1.B.23CBPions, small molecules400-95014-16B(G-)1SomA of Synechococcus sp
1.B.24MBPions, small molecules200-250MspA of Mycobacterium smegmatis
1.B.25Oprions, small moleculesc. 450B(G-)0OprD2 of Pseudomonas aeruginosa
1.B.26CDPcyclodextrins c. 350B(G-)0CymA of Klebsiella oxytoca
1.B.27HOPions, small molecules200-60018B(G-)1HopE of Helicobacter pylori
1.B.28OEP24ions, small moleculesc. 2007E(P)1OEP24 of Pisum sativum
1.B.29OEP21organic anionsc. 200E(P)1OEP21 of Pisum sativum
1.B.30OEP16organic cationsc. 150(2 b, 1 a)4E(P)1OEP16 of Pisum sativum
1.B.31MomPions, small moleculesc. 400B(G-)1MomP of Campylobacter jejuni
1.B.32FomPions, small moleculesc. 400(16)3B(G-)0FomA of Fusobacterium nucleatum
1.B.33VC/NPacetylated chitooligomers; ions, small molecules300-400B(G-)1ChiP of Vibrio furnissii
1.B.34PorA ions, small moleculesc. 50B0PorA of Corynebacterium glutamicum

1.C Pore-forming toxins

These proteins and peptides are synthesized by one cell and secreted for insertion into the membrane of another cell where they form transmembrane pores. They may exert their toxic effects by allowing the free flow of electrolytes and other small molecules across the membrane, or they may allow entry into the target cell cytoplasm of a toxin protein that ultimately kills or controls the cell. Both ribosomally synthesized large protein and small peptide toxins are included in this category.

TC no. a Family Substrates b Size range c Number of transmembrane segmentsd Distributione nf Examples
1.C.1Colicinions, small molecules400-700 (150-180 for the channel domain)2B2colicin Ia of E.coli
1.C.2ICPions, small molecules600-14006B2CryIAa of Bacillus thuringiensis
1.C.3aHLions, small molecules300-350(2)2b-strandsa-hemolysin of Staphylococcus aureus
1.C.4Aerolysinions, small molecules450-500(2)2b-strandsB, E (Pl)1aerolysin of Aeromonas hydrophila
1.C.5e-toxinK+; ions, small moleculesc. 3501B1b-toxin of Clostridium perfringens
1.C.6YKT-K1cations, ATP, small moleculesc. 300[2(a-subunit) + 1(b-subunit)]nE0yeast killer toxin of Saccharomyces cerevisiae
1.C.7DTDT, A-chain (protein)550-600(2)n n = variableBp0diphtheria toxin (DT) of corynebacteriophage
1.C.8BTTBTT, L-chains1150-1350(2)nB1botulinum and tetanus toxin channels of Clostridium species
1.C.9VacAions, small molecules1250-1350(3)nB0VacA of Helicobacter pylori
1.C.10HlyEions (moderately cation-selective)c. 300(2)nB0HlyE of Escherichia coli
1.C.11RTX-toxinions, small molecules250-1850(3)nB2HlyA of Escherichia coli
1.C.12TACions, metabolites, proteins450-600(2 b-hairpins)n n=30-60B2perfringolysin O of Clostridium perfringens
1.C.13Ctxionsc. 300(?)5?Bp0leucocidin cytotoxin Ctx of Pseudomonas aeruginosa phage jCTX
1.C.14CHLions and other solutes450-750(0-1)5?B1HlyA of Vibrio cholerae
1.C.15WSPsmall moleculesc. 400(0)nE(An)0whipworm stichosome porin of Trichuris trichiura
1.C.16Magaininsmall solutes, electrolytes, water80-300(2)nE(An)1magainin precursor of Xenopus laevis
1.C.17Cecropinsmall solutes, electrolytes, water30-65(0-1)nE(An)2cecropin A, B and C precursor of Hyalophora cecropia
1.C.18Melittinsmall solutes, 25-70(0-2)nE(An)0melittin major precursor of electrolytes, water Apis mellifera
1.C.19Defensinsmall solutes, electrolytes, water30-100(0)nE(A)2neutrophil defensin GP-CS1 of Cavia porcellus
1.C.20Nisinsmall solutes, electrolytes, water55-60(0)nB(G+)1nisin precursor of Lactococcus lactis
1.C.21Lacticin 481small solutes, electrolytes, waterc. 50(0)nB(G+)1lacticin 481 of Lactococcus lactis
1.C.22Lactococcin Asmall solutes, electrolytes, water65-75(0-1)nB(G+)lactococcin A precursor of Lactococcus lactis
1.C.23Lactocin Ssmall solutes, electrolytes, water25(1)nB(G+)0lactocin S of Lactobacillus sake L45
1.C.24Pediocinsmall solutes, electrolytes, water40-70(0)nB(G+)1pediocin PA-1 precursor of Pediococcus acidilactic
1.C.25Lactococcin Gsmall solutes, electrolytes, waterc. 40+35(0)nB(G+)0lactococcin G of Lactococcus lactis
1.C.26Lactacin Xsmall solutes, electrolytes, waterc. 75 + 65(2)nB(G+)0LafA and LafX of Lactobacillus johnsonii
1.C.27Divergicin Asmall solutes, electrolytes, waterc. 75(2)nB(G+)0DvnA of Carnobacterium divergens
1.C.28AS-48small solutes, electrolytes, waterc. 100(1)nB(G+)0AS-48 of Enterococcus faecalis S-48 plasmid pMB2
1.C.29Plantaricin EFsmall solutes, electrolytes, waterc. 55+50(0)nB(G+)0PlnE, F of Lactobacillus plantarum
1.C.30Plantaricin JKsmall solutes, electrolytes, waterc. 55 + 55(0)nB(G+)0PlnJ, K of Lactobacillus plantarum
1.C.31Colicin Vions, small moleculesc. 100(1-2)nB0colicin V of Escherichia coli
1.C.32Mastoparansmall molecules c. 15 barrel stove (1)nE (An)1mastoparan of Vespa xanthoptera
1.C.33Cathilicidinsmall molecules90-250(1)nE (An)2pre-myeloid cathilicidin 1 of Equus caballus
1.C.34Tachyplesinsmall moleculesc. 80(1)nE (An)1tachyplesin I of Tachyplesus tridentatus
1.C.35Amoebaporesmall moleculesc. 100(1)nE (Pr)1amoebapore of Entamoeba histolytica
1.C.36IIITCPproteins300-600(2)nB1type III-protein secretion target cell pore protein, YopB of Yersinia pseudotuberculosis
1.C.37Lactococcin 972small molecules50-100(1)nB0lactococcin 972 of Lactococcus lactis
1.C.38Equinatoxinsmall molecules150-250(1)3 or (1)4E (An)2equinatoxin of Actinia tenebrosa
1.C.39CPC9ions, small solutes500-600(1)nE(An)2C9 of Equus caballus
1.C.40BPIPcholesterol, lipopolysaccharide250-500(1)nE(An)2BPIP precursor of Homo sapiens
1.C.41HBLions, small solutes150-400(2)nB1hemolysin YhlA of Edwardsiella tarda
1.C.42BAPAprotein toxin, small molecules150-800[3 (b?)]nB(G+)0iotatoxin Ib of Clostridium perfringens
1.C.43Lyseninvarious solutesc. 300(1)nE(An)0lysenin of Eisenia foetida
1.C.44PTsmall molecules45-47 (precursors: 70-140) two antiparallel a-helices and two antiparallel b-strandsE(Pl)viscotoxin B precursor of Viscum album
1.C.45PDsmall molecules45-54 (precursors: 80-120)triple-stranded antiparallel b-sheets and 1 a-helixE(Pl)2g-thionin of Nicotiana tabacum
1.C.46CNPcationssmall peptides (precursors: 80-140)(0)nE(An)2C-type natriuretic peptide precursor of Homo sapiens
1.C.47Insect defensinions small peptides (precursors: 80-120)(0-2)nE(An)phormicin precursor of Protophormia terranovae
1.C.48PPF ions 200-3001-3E(An)2major prion protein precursor Prp of Ovis aries
1.C.49Amylin ions25-1500-1E(An)2amylin of Canis familiaris
1.C.50APP ions50-9000-2E(An)2amyloid b-protein peptide of Rattus norvegicus
1.C.51Pilosulin ionsc. 1001E(An)1philosin I of Myrmecia pilosula
1.C.52Dermaseptin ions70-801E(An)1brevinin-2EF of Rana esculenta
1.C.53Bacteriocin AS-48ions and small molecules 70 (cyclic) (precursors: 105)1B(G+)0bacteriocin AS-48 of Enterococcus faecalis
1.C.54ST-Bshiga toxin A(89)51-2Bp1verotoxin B-chain of Escherichia coli
1.C.55VirE2proteins, DNA, anions500-600b-structure (b-barrel?)B1VirE2 of Agrobacterium tumefaciens
1.C.56HrpZcations, small molecules c. 350(2)nB0HrpZ cation-selective channel protein of Pseudomonas syringae
1.C.57CCTtoxin domain, ions, other solutes2100-32002B0cytotoxin B of Clostridium difficile
1.C.58Microcin E492univalent cationsc. 100(0)nB0microcin C24 of Escherichia coli
1.D Non-ribosomally synthesized channels

These molecules, often chains of L- and D-amino acids and of the hydroxy acids lactate and b-hydroxybutyrate, form oligomeric trans-membrane channels. Voltage may induce channel formation by promoting assembly of the oligomeric pore-forming structure. These "depsipeptides" are often made by bacteria and fungi and are used as agents of biological warfare. Other substances, completely lacking amino acids, may also be involved in channel formation.

TC no. a Family Substrates b Size range c Number of transmembrane segmentsd Distributione nf Examples
1.D.1Gramicidin A univalent cations15 L- and D-amino acids0.5B0gramicidin A Bacillus brevis
1.D.2Syringomycincationscyclic lipodepsipeptide containing nonprotein amino acids1?B1syringomycin of Pseudomonas syringae
1.D.3Syringopeptin cationscyclic lipodepsipeptide containing nonprotein amino acids1?B1syringopeptin SP22 of Pseudomonas syringae
1.D.4Tolaasin cations lipodepsipeptide (contains D-amino acids, hydroxy acids, and fatty acids)1?B1tolaasin of Pseudomonas tolaasii
1.D.5Alamethicin ions20-21 amino acids including nonprotein amino acids1?E(Fu)1longibrachin I of Trichoderma longibranchiatum
1.D.6cPHB-CCDNA uptakePHB, Ca2+ and polyphosphate-B1poly-(R)-3-hydroxybutyrate channel of Streptomyces lividans
1.D.7Beticolinionsmostly naphthocycloheptaxanthene acetates, c. 640 Da-E(Fu)1beticolin 0 of Cercospora beticola
1.D.8Saponin various solutesglycosylated triterpenoids, steroids and alkaloids-E(Pl)0avenacoside A of Avena sativa
1.D.9PG-IC ionspolyglutamine ion channel, about 60 amino acid residues-E(An)1polyglutamine of Homo sapiens
1.D.10Ceramide small proteinslipids-E(An)1C2-ceramide of Glycine max
1.D.11PEAmainly K+, also organic compoundsno amino acids, c. 920 Da-B1amphotericin B of Streptomyces nodosus
1.D.12TyrAvarious solutes8-12 amino acids-B1surfactin of Bacillus subtilis

1.E Holins

This subclass comprises integral membrane proteins that control the access of phage-encoded cell-wall-lysing enzymes, the endolysins, by rapid formation of a homo-oligomeric lesion in the membrane. The presence of a holin and of endolysin is essential for bacteriophage-induced bacterial lysis. Some holins are encoded within bacterial genomes and probably promote programmed cell death. The holins are an extremely diverse functional group and are given here the status of a subclass.

TC no. a Family Substrates b Size range c Number of transmembrane segmentsd Distributione nf Examples
1.E.1P21 holin endolysin, ions, small metabolites70-1002 B, Bp1lysis protein S of Escherichia coli
1.E.2b holinendolysin100-1503B, Bp1lysis protein S of phage b
1.E.3P2 holinendolysin90-1003Bp1lysis protein TM of phage P2
1.E.4LydA holinendolysinc. 1102B, Bp0LydA protein of Escherichia coli
1.E.5PRD1 holinendolysin901Bp0protein M of phage PRD1
1.E.6T7 holinendolysin45-701Bp1Gb 17.5 Phage T7
1.E.7HP1 holinendolysin70-901B, Bp1holin of Haemophilus influenzae phage HP1
1.E.8T4 holinendolysin200-2501Bp1lysis protein of phage T4
1.E.9T4 Immunityendolysinc. 802Bp1immunity protein of phage T4 holin
1.E.10f29 holinprotein100-1502Bp1GP14 of Bacillus phage Phi 29
1.E.11f11 holinendolysin50-2002Bp0holin of Staphylococcus phage Phi11
1.E.12fAdh holinendolysin1141Bp0holin of Lactobacillus gasseri phage Phi Adh
1.E.13fU53 holinendolysinc. 661Bp0holin of Lactococcus lactis phage U53
1.E.14LrgA holinendolysin100-1504B1LrgA of Staphylococcus aureus
1.E.15ArpQ holinendolysinc. 602B0ArpQ of Enterococcus hirae
1.E.16Cph1 holinendolysinc. 1353Bp0Cph1 holin of Streptococcus pneumoniae phage Cp-1
1.E.17BlyA holinendolysinc. 701Bp0BlyA of cp32 prophage from Borrelia burgdorferi
1.E.18R1t holinlysin75-802Bp0Orf49 holin of L. lactis phage r1t
1.E.19TcdE holintoxinc. 1603B0TcdE of Clostridium difficile

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 2
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