The brown protein of Drosophila melanogaster is similar to the white protein and to components of active transport complexes.
The brown gene of Drosophila melanogaster is required for deposition of pteridine pigments in the compound eye and other tissues. We isolated a ca. 150-kilobase region including brown by microdissection and chromosome walking using cosmids. Among the cDNAs identified by hybridization to the cosmids, one class hybridized to a genomic region that is interrupted in two brown mutants, bw and In(2LR)CK, and to 2.8- and 3.0-kilobase poly(A)+ RNAs which are altered in the mutants. Nucleotide sequencing of these cDNAs revealed that the two transcripts differ as a consequence of alternative poly(A) addition and that both encode the same predicted protein of 675 amino acids. Searches of available databases for amino acid sequence similarities detected a striking overall similarity of this predicted protein to that of the D. melanogaster white gene. The N-terminal portion aligned with the HisP family of membrane-associated ATP-binding proteins, most of which are subunits of active transport complexes in bacteria, and to two regions of the multidrug resistance P-glycoprotein. The C-terminal portion showed a structural similarity to integral membrane components of the same complexes. Taken together with earlier biochemical evidence that brown and white gene products are necessary for uptake of a pteridine precursor and genetic evidence that brown and white proteins interact, our results are consistent with suggestions that these proteins are subunits of a pteridine precursor permease.
Dreesen
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Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Johnson
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DH
Henikoff
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D018528:ATP-Binding Cassette Transporters; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001693:Biological Transport, Active; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005136:Eye Proteins; D005796:Genes; D007301:Insect Hormones / Q000235:genetics*; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D011679:Pupa; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
D018528:ATP-Binding Cassette Transporters; D029721:Drosophila Proteins; D005136:Eye Proteins; D007301:Insect Hormones; C059253:bw protein, Drosophila; C059254:w protein, Drosophila; D004247:DNA