Due to improvement work scheduled on this server, some services may not be fully operational on Tuesday December 12 daytime (CEST).
PROSITE documentation PDOC00364 [for PROSITE entry PS50929]

ABC transporter integral membrane type-1 domain profiles





Description

ABC transporters belong to the ATP-Binding Cassette (ABC) superfamily which uses the hydrolysis of ATP to energize diverse biological import and export systems (see <PDOC00185>). ABC transporters are minimally constituted of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These regions can be found on the same protein (mostly in eukaryotes and bacterial exporters) or on two different ones (mostly bacterial importers) [1,2,3]. The function of the integral inner-membrane protein is to translocate the substrate across the membrane. Studies of P-glycoprotein function indicate that residues lining the proposed chamber opening (residues of TM2, TM5 and TM6) play an important role in substrate recognition [4].

In exporters and eukaryotes, ABC transporters consist of a single polypeptide composed of an N-terminal domain of approximately 320 residues, apparently containing six transmembrane segments, fused to a highly conserved ABC-ATPase domain of approximately 260 residues [5,6,7]. In some cases an N-terminal peptidase domain of 130-150 residues appended to the TMD is also found, which may contain additional transmembrane segments as in the HlyB subfamily [8,9].

The 3D structure of the E. coli lipid A flippase MsbA homodimer reveals that association of the two transmembrane domains forms one chamber that adopt a cone-shape which extends along a pseudo two-fold axis perpendicular to the cell membrane (see <PDB:1JSQ>) [10]. The chamber has an opening on either side of the membrane to provide free access for the lipid substrate from the cytoplasmic leaflet of the lipid bilayer, while excluding molecules from the outer leaflet. The chamber openings are defined by intramolecular interactions between TM2 of one monomer and TM5 of the other. The residues lining the chamber are contributed by all 12 transmembrane α-helices [10,11].

In importers (found only in prokaryotes or archaea) most ABC transporters consist of four domains usually encoded by independent polypeptides, two ABC modules and two TMDs which are thought to contain six transmembrane regions [12,13]. The approximately 30 kD TMD displays a distinctive signature, the EAA motif, a 20 amino acid conserved sequence located about 100 residues from the C-terminus. The motif is hydrophilic and has been found to reside in a cytoplasmic loop located between the penultimate and the antepenultimate transmembrane segment in all proteins with a known topology [14,15,16]. It appears to play an important role in ensuring the correct assembly of the prokaryotic ABC transport complex [17] and constituting an interaction site with the so-called helical domain of the ABC module [18,19]. The TMDs form either homo-oligomeric channels or associate with another TMD to form hetero-oligomers.

The 3D structure of the E. coli BtuCD proteins has been solved [20]. It consists of two copies of the transmembrane domain BtuC and two copies of the ATPase BtuD (see <PDB:1L7V>). Each BtuC subunit is composed of 10 α-helices, rather than the six of MsbA, and these are packed together in a more intricated manner than MsbA. Helices two-five and seven-ten are related by a pseudo-two-fold rotation axis, while helices one and six are nearly perpendicular to the plane of the membrane. The prominent cytoplasmic loop between helices six and seven folds into two short helices, L1 and L2, which make extensive contacts with BtuC. The conserved sequence within the L1-L2 region may represent a general interface between the TMD and NBD [11,20].

During the transport cycle a conformational change involved by the NBD domain has been described for this two kinds of transmembrane domains like those of Pgp and MalFGK2 complex [21,22].

Integral membrane components of ABC complex have been shown to be evolutionary related and proteins known to belong to this family are classified in several functional subfamilies depending on the substrate used [E1]. All different types of transporters with a functional attribution are listed below (references are only provided for recently characterized proteins).

In prokaryotes:

Active import transport system components:

  • Carbohydrate uptake transporter.
  • Cobalt uptake transporter.
  • Ferric iron uptake transporter.
  • Hydrophobic amino acid uptake transporter.
  • Iron Chelate uptake transporter.
  • Manganese/Zinc/Iron chelate uptake transporter.
  • Molybdate uptake transporter.
  • Nitrate/Nitrite/Cyanate uptake transporter.
  • Peptide/Opine/Nickel uptake transporter.
  • Phosphate uptake transporter.
  • Phosphonate uptake transporter.
  • Polyamine/Opine/Phosphonate uptake transporter.
  • Quaternary amine uptake transporter.
  • Sulfate uptake transporter.
  • Taurine uptake tranporter (tauC).
  • Thiamin uptake transporter (thiamin/thiamin pyrophosphate).
  • Vitamine B12 uptake tranporter (btuC).

Active export transport system components:

  • Capsular polysaccharide exporter (kpsT).
  • Drug exporter-1: daunorubicin/doxorubicin (drrA); oleandomycin (oleC4).
  • Drug resistance ATPase-1.
  • Drug/siderophore exporter-3.
  • Glucan exporter: β-(1,2)-glucan export (chvA/ndvA).
  • Lipid A exporter (msbA).
  • Lantibiotic exporter: hemolysin/bacteriocin (cylB).
  • Lipooligosaccharide exporter (nodulation protein nodI from Rhizobium).
  • Lipopolysaccharide exporter (rbfA).
  • Micrococin B17 exporter (mcbF).
  • Micrococin J25 exporter (mcjD).
  • Peptide-2 exporter: competence factor (comA/comB).
  • Peptide-3 exporter: modified cyclic peptide (syrD.
  • Protein-1 exporter: hemolysin (hlyB).
  • Protein-2 exporter: colicin V(cvaB).
  • S-layer protein exporter (rsaD/sapD).
  • Techoic Acid Exporter (tagH).

In eukaryotes:

  • ALDP, a peroxisomal protein involved in X-linked adrenoleukodystrophy.
  • Antigen peptide transporters 1 (TAP1, PSF1, RING4, HAM-1, mtp1) and 2 (TAP2, PSF2, RING11, HAM-2, mtp2), which are involved in the transport of antigens from the cytoplasm to a membrane-bound compartment for association with MHC class I molecules.
  • Cystic fibrosis transmembrane conductance regulator (CFTR), which is most probably involved in the transport of chloride ions.
  • Drosophila proteins white (w) and brown (bw), which are involved in the import of ommatidium screening pigments.
  • Fungal elongation factor 3 (EF-3).
  • Multidrug transporters (Mdr1) (P-glycoprotein), a family of closely related proteins which extrude a wide variety of drugs out of the cell.
  • 70 Kd peroxisomal membrane protein (PMP70).
  • Sulfonylurea receptor, a putative subunit of the B-cell ATP-sensitive potassium channel.

We have developed two profiles to distinguish between these two kinds of ABC transmembrane domains. The first one recognizes the TMD in protein families where TMD and NBD are on separate proteins. The second one picks up proteins where TMD and NBD are fused. Both profiles cover the entire six transmembrane region.

Note:

These profiles replace a pattern (PS00402) whose specificity was inadequate.

Last update:

November 2003 / Pattern removed, profiles added and text revised.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

ABC_TM1F, PS50929; ABC transporter integral membrane type-1 fused domain profile  (MATRIX)

ABC_TM1, PS50928; ABC transporter integral membrane type-1 domain profile  (MATRIX)


References

1AuthorsHolland I.B., Cole S.P.C., Kuchler K., Higgins C.F.
Source(In) ABC proteins from bacteria to man, Academic Press, San Diego, (2003).

2AuthorsHolland I.B., Blight M.A.
SourceJ. Mol. Biol. 293:381-399(1999).

3AuthorsSaurin W., Hofnung M., Dassa E.
TitleGetting in or out: early segregation between importers and exporters in the evolution of ATP-binding cassette (ABC) transporters.
SourceJ. Mol. Evol. 48:22-41(1999).
PubMed ID9873074

4AuthorsAmbudkar S.V., Dey S., Hrycyna C.A., Ramachandra M., Pastan I., Gottesman M.M.
TitleBiochemical, cellular, and pharmacological aspects of the multidrug transporter.
SourceAnnu. Rev. Pharmacol. Toxicol. 39:361-398(1999).
PubMed ID10331089
DOI10.1146/annurev.pharmtox.39.1.361

5AuthorsReizer J., Reizer A., Saier M.H. Jr.
TitleA new subfamily of bacterial ABC-type transport systems catalyzing export of drugs and carbohydrates.
SourceProtein Sci. 1:1326-1332(1992).
PubMed ID1303751

6AuthorsVazquez M., Santana O., Quinto C.
TitleThe NodL and NodJ proteins from Rhizobium and Bradyrhizobium strains are similar to capsular polysaccharide secretion proteins from gram-negative bacteria.
SourceMol. Microbiol. 8:369-377(1993).
PubMed ID8316086

7AuthorsPeelman F., Labeur C., Vanloo B., Roosbeek S., Devaud C., Duverger N., Denefle P., Rosier M., Vandekerckhove J., Rosseneu M.
TitleCharacterization of the ABCA transporter subfamily: identification of prokaryotic and eukaryotic members, phylogeny and topology.
SourceJ. Mol. Biol. 325:259-274(2003).
PubMed ID12488094

8AuthorsHavarstein L.S., Diep D.B., Nes I.F.
TitleA family of bacteriocin ABC transporters carry out proteolytic processing of their substrates concomitant with export.
SourceMol. Microbiol. 16:229-240(1995).
PubMed ID7565085

9AuthorsZhong X., Kolter R., Tai P.C.
TitleProcessing of colicin V-1, a secretable marker protein of a bacterial ATP binding cassette export system, requires membrane integrity, energy, and cytosolic factors.
SourceJ. Biol. Chem. 271:28057-28063(1996).
PubMed ID8910417

10AuthorsChang G., Roth C.B.
SourceScience 293:1793-1800(2001).

11AuthorsBorges-Walmsley M.I., McKeegan K.S., Walmsley A.R.
SourceBiochem. J. 0:0-0(2003).

12AuthorsAmes G.F.-L.
SourceAnnu. Rev. Biochem. 55:397-425(1986).

13AuthorsHiggins C.F., Hyde S.C., Mimmack M.M., Gileadi U., Gill D.R., Gallagher M.P.
SourceJ. Bioenerg. Biomembr. 22:571-592(1990).

14AuthorsDassa E., Hofnung M.
SourceEMBO J. 4:2287-2293(1985).

15AuthorsSaurin W., Koster W., Dassa E.
SourceMol. Microbiol. 12:993-1004(1994).

16AuthorsPearce S.R., Mimmack M.L., Gallagher M.P., Gileadi U., Hyde S.C., Higgins C.F.
SourceMol. Microbiol. 6:57-57(1992).

17AuthorsSchneider E., Hunke S.
SourceFEMS Microbiol. Rev. 22:1-20(1998).

18AuthorsHunke S., Mourez M., Jehanno M., Dassa E., Schneider E.
SourceJ. Biol. Chem. 275:15526-15534(2000).

19AuthorsMourez M., Hofnung M., Dassa E.
SourceEMBO J. 16:3066-3077(1997).

20AuthorsLocher K.P., Lee A.T., Rees D.C.
SourceScience. 296:1091-108.(2002).

21AuthorsRosenberg M.F., Velarde G., Ford R.C., Martin C., Berridge G., Kerr I.D., Callaghan R., Schmidlin A., Wooding C., Linton K.J., Higgins C.F.
SourceEMBO J. 20:5615-5625(2001).

22AuthorsChen J., Sharma S., Quiocho F.A., Davidson A.L.
SourceProc. Natl. Acad. Sci. U.S.A. 98:1525-1530(2001).

E1Sourcehttp://www.tcdb.org/tcdb/index.php?tc=3.A.1



PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to
Prosite License or see: prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)