ABCA6, a novel a subclass ABC transporter.
Here we report the cDNA cloning of a novel member of the ABC A transporter subfamily from human macrophages. The identified coding sequence is of 5.0 kb size and contains an open reading frame which encodes a 1617 amino acid polypeptide. Structurally, the putative ABC transporter protein product consists of two tandemly oriented subunits, each composed of a transmembrane domain followed by a nucleotide binding fold, and thus conforms to the group of full-size ABC transporters. We also demonstrate the existence of an alternative transcript that codes for a 637 amino acid protein variant bearing the features of a truncated half-size transporter. Among the human ABC transporter subfamily A the novel transporter shows highest protein sequence homology with ABCA8 (60%), followed by ABCA2 (32%) and ABCA1 (32%), respectively. In agreement with the proposed classification, the novel transporter was designated ABCA6. The ABCA6 gene is ubiquitously expressed with highest mRNA levels in liver, lung, heart and brain. Analysis of the genomic organization demonstrated that the ABCA6 gene is composed of 38 exons which extend across a region of 62 kb size on chromosome 17q24.2. Based on its structural features and its cholesterol-responsive regulation ABCA6 is potentially involved in macrophage lipid homeostasis.
Kaminski
W E
WE
Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg, 93042, Germany.
Wenzel
J J
JJ
Piehler
A
A
Langmann
T
T
Schmitz
G
G
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000145:classification / Q000235:genetics*; D017398:Alternative Splicing; D001921:Brain / Q000378:metabolism; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D006801:Humans; D007438:Introns; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D020161:Physical Chromosome Mapping; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
C577836:ABCA1 protein, human; C418186:ABCA2 protein, human; C434046:ABCA6 protein, human; C582675:ABCA8 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D018076:DNA, Complementary; D012333:RNA, Messenger