title: The human ABCG4 gene is regulated by oxysterols and retinoids in monocyte-derived macrophages.
abstract: Here we report the induction of gene expression of ABCG4, a member of the ABC transporter subfamily G, from human macrophages by oxysterols and retinoids, agonists of the nuclear receptors LXR and RXR. The cloned ABCG4 transcript has a size of 3.5 kb and contains an open reading frame which encodes a polypeptide of 646 amino acids. Structurally, the putative ABC transporter protein consists of a nucleotide binding fold followed by a cluster of six transmembrane-spanning domains and thus conforms to the group of half-size ABC transporters. Among the human ABC transporter subfamily G members the novel transporter shows highest protein sequence homology and identity to ABCG1 (84 and 72%, respectively). Analysis of the genomic organization demonstrates that the ABCG4 gene is composed of at least 14 exons which extend across a region of 12.6 kb in size on chromosome 11q23.3. Based on its structural features and an LXR/RXR-responsive regulation similar to the cellular lipid export protein ABCA1, we conclude that ABCG4 may be involved in macrophage lipid homeostasis.
authors.affiliation: Macrophage Metabolism, Institut für Arterioskleroseforschung, Westfälische Wilhelms-Universität, Domagkstrasse 3, 48149 Münster, Germany. engeltho@uni-muenster.de
authors.forename: T
authors.initials: T
authors.lastname: Engel
authors.forename: S
authors.initials: S
authors.lastname: Lorkowski
authors.forename: A
authors.initials: A
authors.lastname: Lueken
authors.forename: S
authors.initials: S
authors.lastname: Rust
authors.forename: B
authors.initials: B
authors.lastname: Schlüter
authors.forename: G
authors.initials: G
authors.lastname: Berger
authors.forename: P
authors.initials: P
authors.lastname: Cullen
authors.forename: G
authors.initials: G
authors.lastname: Assmann
mesh_terms: D000070996:ATP Binding Cassette Transporter, Subfamily G; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D005091:Exons; D005786:Gene Expression Regulation / Q000187:drug effects*; D015894:Genome, Human; D006801:Humans; D007438:Introns; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology; D012176:Retinoids / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid
chemical_list: C419353:ABCG1 protein, human; C439766:ABCG4 protein, human; D000070996:ATP Binding Cassette Transporter, Subfamily G; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; C486685:Abcg4 protein, mouse; D018076:DNA, Complementary; D012176:Retinoids