title: PXA1, a possible Saccharomyces cerevisiae ortholog of the human adrenoleukodystrophy gene.
abstract: The adrenoleukodystrophy protein (ALDp) is an ATP-binding cassette (ABC) transporter in the human peroxisome membrane. It is defective in X chromosome-linked adrenoleukodystrophy (ALD), a neurodegenerative disorder with impaired peroxisomal oxidation of very long chain fatty acids. We report cloning and characterization of PXA1, a yeast gene encoding a protein (Pxa1p) exhibiting high similarity to ALDp. Disruption of PXA1 results in impaired growth on oleic acid and reduced ability to oxidize oleate. Pxa1p is peroxisome associated; however, in the PXA1 mutant yeast, as in ALD cells, peroxisomes are morphologically intact. Disruption of a second yeast gene, YKL741, which encodes a more distantly related ALDp homolog (Yk174p), in either wild-type or PXA1 mutant yeast, results in a growth phenotype identical to that of the PXA1 mutant. This result suggests that Yk1741p and Pxa1p may be subunits of the same transporter. Sequence analysis of Pxa1p, ALDp, and related ABC transporters reveals a possible fatty acid binding domain and a 14-amino acid EAA-like motif, previously described only in prokaryotes. Because of the similarities in sequence and function, we propose that Pxa1p is the Saccharomyces cerevisiae ortholog of ALDp.
authors.affiliation: Kennedy Krieger Institute, Baltimore, MD, USA.
authors.forename: N
authors.initials: N
authors.lastname: Shani
authors.forename: P A
authors.initials: PA
authors.lastname: Watkins
authors.forename: D
authors.initials: D
authors.lastname: Valle
mesh_terms: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics*; D000326:Adrenoleukodystrophy / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002374:Catalase / Q000032:analysis / Q000378:metabolism; D003001:Cloning, Molecular; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008830:Microbodies / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014960:X Chromosome
chemical_list: C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; D008565:Membrane Proteins; C098338:PXA1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D002374:Catalase