title: Identification and characterization of a novel member of the heterodimeric amino acid transporter family presumed to be associated with an unknown heavy chain.
abstract: We identified a novel amino acid transporter designated Asc-2 (for asc-type amino acid transporter 2). Asc-2 exhibited relatively low but significant sequence similarity to the members of the heterodimeric amino acid transporters. The cysteine residue responsible for the disulfide bond formation between transporters (light chains) and heavy chain subunits in the heterodimeric amino acid transporters is conserved for Asc-2. Asc-2 is, however, not colocalized with the already known heavy chains such as 4F2 heavy chain (4F2hc) or related to b(0,+) amino acid transporter (rBAT) in mouse kidney. Because Asc-2 solely expressed or coexpressed with 4F2hc or rBAT did not induce functional activity, we generated fusion proteins in which Asc-2 is connected with 4F2hc or rBAT. The fusion proteins were sorted to the plasma membrane and expressed the function corresponding to the Na(+)-independent small neutral amino acid transport system asc. Distinct from the already identified system asc transporter Asc-1 which is associated with 4F2hc, Asc-2-mediated transport is less stereoselective and did not accept some of the high affinity substrates of Asc-1 such as alpha-aminoisobutyric acid and beta-alanine. Asc-2 message was detected in kidney, placenta, spleen, lung, and skeletal muscle. In kidney, Asc-2 protein was present in the epithelial cells lining collecting ducts. In the Western blot analysis on mouse erythrocytes and kidney, Asc-2 was detected as multiple bands in the nonreducing condition, whereas the bands shifted to a single band at lower molecular weight, suggesting the association of Asc-2 with other protein(s) via a disulfide bond. The finding of Asc-2 would lead to the establishment of a new subgroup of heterodimeric amino acid transporter family which includes transporters associated not with 4F2hc or rBAT but with other unknown heavy chains.
authors.affiliation: Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Chairoungdua
authors.forename: Y
authors.initials: Y
authors.lastname: Kanai
authors.forename: H
authors.initials: H
authors.lastname: Matsuo
authors.forename: J
authors.initials: J
authors.lastname: Inatomi
authors.forename: D K
authors.initials: DK
authors.lastname: Kim
authors.forename: H
authors.initials: H
authors.lastname: Endou
mesh_terms: D000595:Amino Acid Sequence; D027182:Amino Acid Transport System y+; D026905:Amino Acid Transport Systems / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D026923:Amino Acid Transport Systems, Basic; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000378:metabolism; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013154:Spleen / Q000502:physiology / Q000503:physiopathology; D013379:Substrate Specificity; D014018:Tissue Distribution; D014982:Xenopus laevis
chemical_list: D027182:Amino Acid Transport System y+; D026905:Amino Acid Transport Systems; D026923:Amino Acid Transport Systems, Basic; D000596:Amino Acids; D002352:Carrier Proteins; D027282:Fusion Regulatory Protein 1, Heavy Chain; D008562:Membrane Glycoproteins; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; C445322:Slc7a12 protein, mouse; C499488:Slc7a9 protein, mouse