ABCA10, a novel cholesterol-regulated ABCA6-like ABC transporter.
We recently identified several novel members of the A subclass of ABC transporters. In this study, we report the cloning of an additional ABC A subfamily transporter, denoted ABCA10, from macrophages. The coding sequence of ABCA10 is of 4.6 kb size and codes for a 1543-amino acid protein that bears the structural features of a full-size ABC transporter. Intriguingly, ABCA10 contains a PEST sequence downstream of the N-terminal transmembrane domain which may be potentially involved in the control of its turnover rate by proteasomal degradation. Several distinct ABCA10 transcripts are expressed in human macrophages that predict the existence of various truncated forms of the novel transporter. Moreover, we identified seven single nucleotide polymorphisms in ABCA10 transcripts. ABCA10 displays high amino acid sequence homology with ABCA6 (63%), ABCA8 (62%), and ABCA9 (63%), respectively, known members of the subgroup of ABCA6-like transporters. Like other transporters of this subfamily, ABCA10 mRNA is ubiquitously expressed and highest gene expression levels are detectable in heart, brain, and the gastrointestinal tract. Analysis of the gene structure demonstrated that the ABCA10 gene consists of 40 exons that extend across a genomic region of approximately 97kb size (Chr. 17q24.3). ABCA10 mRNA is expressed in similar quantities in monocytes and M-CSF differentiated macrophages. Importantly, ABCA10 expression is suppressed by cholesterol import into macrophages, indicating that it is a cholesterol-responsive gene. Our results identify ABCA10 as a novel member of the group of ABCA6-like transporters and suggest its involvement in macrophage lipid homeostasis.
Wenzel
Jürgen J
JJ
Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg D-93042, Germany.
Kaminski
Wolfgang E
WE
Piehler
Armin
A
Heimerl
Susanne
S
Langmann
Thomas
T
Schmitz
Gerd
G
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology*; D000595:Amino Acid Sequence; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D006801:Humans; D007438:Introns; D050356:Lipid Metabolism; D008264:Macrophages / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
C476234:ABCA10 protein, human; C434046:ABCA6 protein, human; D018528:ATP-Binding Cassette Transporters; D018076:DNA, Complementary; D010455:Peptides; D012333:RNA, Messenger; D012313:RNA; D002784:Cholesterol