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- *************************************
- * ABC transporters family signature *
- *************************************
-
- On the basis of sequence similarities a family of related ATP-binding
- proteins has been characterized [1 to 5]. These proteins are associated with a
- variety of distinct biological processes in both prokaryotes and eukaryotes,
- but a majority of them are involved in active transport of small hydrophilic
- molecules across the cytoplasmic membrane. All these proteins share a
- conserved domain of some two hundred amino acid residues, which includes an
- ATP-binding site. These proteins are collectively known as ABC transporters.
- Proteins known to belong to this family are listed below (references are
- only provided for recently determined sequences).
-
- In prokaryotes:
-
- - Active transport systems components: alkylphosphonate uptake(phnC/phnK/
- phnL); arabinose (araG); arginine (artP); dipeptide (dciAD); ferric
- enterobactin (fepC); ferrichrome (fhuC); galactoside (mglA); glutamine
- (glnQ); glycerol-3-phosphate (ugpC); glycine betaine/L-proline (proV);
- histidine (hisP); iron(III) (sfuC), iron(III) dicitrate (fecE); lactose
- (lacK); leucine/isoleucine/valine (braF/braG;livF/livG); maltose (malK);
- molybdenum (modC); nickel (nikD/nikE); oligopeptide (amiE/amiF;oppD/oppF);
- peptide (sapD/sapF); phosphate (pstB); putrescine (potG); ribose (rbsA);
- spermidine/putrescine (potA); sulfate (cysA); vitamin B12 (btuD).
-
- - Hemolysin/leukotoxin export proteins hlyB, cyaB and lktB.
- - Colicin V export protein cvaB.
- - Lactococcin export protein lcnC [6].
- - Lantibiotic transport proteins nisT (nisin) and spaT (subtilin).
- - Extracellular proteases B and C export protein prtD.
- - Alkaline protease secretion protein aprD.
- - Beta-(1,2)-glucan export proteins chvA and ndvA.
- - Haemophilus influenzae capsule-polysaccharide export protein bexA.
- - Cytochrome c biogenesis proteins cycV and helA.
- - Polysialic acid transport protein kpsT.
- - Cell division associated ftsE protein (function unknown).
- - Copper processing protein nosF from Pseudomonas stutzeri.
- - Nodulation protein nodI from Rhizobium (function unknown).
- - Escehrichia coli proteins cydC and cydD.
- - Subunit A of the ABC excision nuclease (gene uvrA).
- - Erythromycin resistance protein from Staphylococcus epidermidis (gene
- msrA).
- - Tylosin resistance protein from Streptomyces fradiae (gene tlrC) [7].
- - Heterocyst differentiation protein (gene hetA) from Anabaena.
- - Protein P29 from Mycoplasma hyorhinis, a probable component of a high
- affinity transport system.
- - yhbG, a putative protein whose gene is linked with ntrA in many bacteria
- such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas putida,
- Rhizobium meliloti and Thiobacillus ferrooxidans.
- - Escherichia coli hypothetical proteins yabJ, ybbA, ycjW, yddA, and yehX.
-
- In eukaryotes:
-
- - The multidrug transporters (Mdr) (P-glycoprotein), a family of closely
- related proteins which extrude a wide variety of drugs out of the cell (for
- a review see [8]).
- - Cystic fibrosis transmembrane conductance regulator (CFTR), which is most
- probably involved in the transport of chloride ions.
- - 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.
- - 70 Kd peroxisomal membrane protein (PMP70).
- - ALDP, a peroxisomal protein involved in X-linked adrenoleukodystrophy [9].
- - Drosophila proteins white (w) and brown (bw), which are involved in the
- import of ommatidium screening pigments.
- - Fungal elongation factor 3 (EF-3).
- - Yeast STE6 which is responsible for the export of the a-factor pheromone.
- - Yeast MDL1 and MDL2.
- - Yeast SNQ2.
- - Heavy metal tolerance protein hmt1 from fission yeast. This protein is
- probably involved in the transport of metal-bound phytochelatins.
- - mbpX, a hypothetical chloroplast protein from Liverwort.
-
- As a signature pattern for this class of proteins, we use a conserved region
- which is located between the 'A' and the 'B' motifs of the ATP-binding site.
-
- -Consensus pattern: [LIVMFYC]-[SA]-[SAPGVYKQ]-G-[DENQMW]-[KRQAPCLW]-
- [KRNQSTAVM]-[KRACLVM]-[LIVMYPAN]-{PHY}-[LIVMFW]-
- [SAGCLIVP]-{FYWHP}-{KRHP}-[LIVMFYWSTA]
- -Sequences known to belong to this class detected by the pattern: ALL, except
- for sapD and malK from Enterobacter aerogenes.
- -Other sequence(s) detected in SWISS-PROT: 6.
-
- -Note: the ATP-binding region is duplicated in araG, mdl, msrA, rbsA, tlrC,
- uvrA, yejF, Mdr's, CFTR, pmd1 and in EF-3. In some of those proteins, the
- above pattern only detect one of the two copies of the domain.
- -Note: the proteins belonging to this family also contain one or two copies of
- the ATP-binding motifs 'A' and 'B' (see the relevant section).
-
- -Last update: June 1994 / Pattern and text revised.
-
- [ 1] Higgins C.F., Hyde S.C., Mimmack M.M., Gileadi U., Gill D.R.,
- Gallagher M.P.
- J. Bioenerg. Biomembr. 22:571-592(1990).
- [ 2] Higgins C.F., Gallagher M.P., Mimmack M.M., Pearce S.R.
- BioEssays 8:111-116(1988).
- [ 3] Higgins C.F., Hiles I.D., Salmond G.P.C., Gill D.R., Downie J.A.,
- Evans I.J., Holland I.B., Gray L., Buckels S.D., Bell A.W.,
- Hermodson M.A.
- Nature 323:448-450(1986).
- [ 4] Doolittle R.F., Johnson M.S., Husain I., van Houten B., Thomas D.C.,
- Sancar A.
- Nature 323:451-453(1986).
- [ 5] Blight M.A., Holland I.B.
- Mol. Microbiol. 4:873-880(1990).
- [ 6] Stoddard G.W., Petzel J.P., van Belkum M.J., Kok J., McKay L.L.
- Appl. Environ. Microbiol. 58:1952-1961(1992).
- [ 7] Rosteck P.R. Jr., Reynolds P.A., Hershberger C.L.
- Gene 102:27-32(1991).
- [ 8] Gottesman M.M., Pastan I.
- J. Biol. Chem. 263:12163-12166(1988).
- [ 9] Valle D., Gaertner J.
- Nature 361:682-683(1993).
-