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* ABC transporters family signature *
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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).