2003 Fiscal Year Final Research Report Summary
Identification and functional characterization of all the genes of heterodimeric amino acid transporter family by means of whole genome information
| Project/Area Number |
14570085
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Kyorin University |
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Principal Investigator |
KANAI Yoshikatsu Kyorin University, School of Medicine, Professor, 医学部, 教授 (60204533)
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| Co-Investigator(Kenkyū-buntansha) |
IRIBE Yuji Kyorin University, School of Medicine, Assistant Professor, 医学部, 助手 (20348618)
KIM Dokyung Kyorin University, School of Medicine, Assistant Professor, 医学部, 助手 (40327474)
ANZAI Naohiko Kyorin University, School of Medicine, Assistant Professor, 医学部, 助手 (70276054)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Amino acid / transporter / membrane transport / genome / postgenome / SLC / Heterodimeric protein / epithelial transport |
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| Research Abstract |
Heterodimeric amino acid transporters are formed by disulfide bonding of a twelve-membrane spanning protein (catalytic subunit) and a single membrane spanning protein (regulatory subunit). We have performed BLAST searches of human and mouse genome data bases using amino acid sequences of LAT1, BAT1 and CAT1 as queries. We have found 5 new genes, SLC7-N1〜5, as new members of SLC7 family. By searching EST (expressed sequence tag) data bases, we have concluded that two of them (SLC7-N4 and SLC7-N5) are pseudogenes, because they never appear in EST data bases. SLC7-N1 possesses 12 transmembrane domains and is supposed to be a catalytic subunit of heterodimeric amino acid transporters. We have named it AGT-1. AGT-1 protein is found on the basolateral membrane of proximal and distal tubules of mouse kidney. Because AGT-1 is supposed to be linked with unknown regulatory subunit, we have generated fusion proteins in which AGT-1 is connected with known regulatory subunits 4F2hc or rBAT and expressed them in Xenopus oocytes. The fusion proteins appear on the plasma membrane and exhibit the transport of acidic amino acids. SLC7-N2 possesses 14 transmembrane domains and exhibits particularly high affinity to arginine, thus we named it CATS (cationic amino acid transporter 5). CATS is expressed in the syncytio-trophoblast of mouse placenta and supposed to mediate transport of amino acids through the placental barrier as well as to supply placental cells with arginine as a precursor of NO synthesis. SLC7-N3 also possesses 14 transmembrane domains and transports small neutral amino acids as well as small basic amino acids, thus we have named it y^+Asc-1. In this study, the function of all the members of heterodimeric amino acid transporter family has been revealed. The results of this study would provide essential information to establish the basis for the genome-wide analyses of diseases or pathological conditions and facilitate drug design targeting the transporters of interest.
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Research Products
(73 results)
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[Journal Article] High affinity D- and L-serine transporter Asc-1 : cloning and dendritic localization in the rat cerebral and cerebellar cortices.2004
Author(s)
Matsuo H, Kanai Y, Tokunaga M, Nakata T, Chairoungdua A, Ishimine H, Tsukada S, Ooigawa H, Nawashiro H, Kobayashi Y, Fukuda J, Endou H
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Journal Title
Neurosci Lett 358(2)
Pages: 123-126
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression and functional characterization of the system L amino acid transporter in KB human oral epidermoid carcinoma cells.2004
Author(s)
Yoon JH, Kim YB, Kim MS, Park JC, Kook JK, Jung HM, Kim SG, Yoo H, Ko YM, Lee SH, Kim BY, Chun HS, Kanai Y, Endou H, Kim do K
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Journal Title
Cancer Lett 205(2)
Pages: 215-226
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mutations in SLC6A19, encoding BOAT1, cause Hartnup disorder.2004
Author(s)
Kleta R, Romeo E, Ristic Z, Ohura T, Stuart C, Arcos-Burgos M, Dave MH, Wagner CA, Camargo SR, Inoue S, Matsuura N, Helip-Wooley A, Bockenhauer D, Warth R, Bernardini I, Visser G, Eggermann T, Lee P, Chairoungdua A, Jutabha P, Babu E, Nilwarangkoon S, Anzai N, Kanai Y, Verrey F, Gahl WA, Koizumi A
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Journal Title
Nat Genet 36(9)
Pages: 999-1002
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The multivalent PDZ domain-containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus.2004
Author(s)
Anzai N, Miyazaki H, Noshiro R, Khamdang S, Chairoungdua A, Shin HJ, Enomoto A, Sakamoto S, Hirata T, Tomita K, Kanai Y, Endou H
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Journal Title
J Biol Chem 279(44)
Pages: 45942-45950
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] System L-amino acid transporters are differently expressed in rat astrocyte and C6 glioma cells.2004
Author(s)
Kim do K, Kim IJ, Hwang S, Kook JH, Lee MC, Shin BA, Bae CS, Yoon JH, Ahn SG, Kim SA, Kanai Y, Endou H, Kim JK
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Journal Title
Neurosci Res 50(4)
Pages: 437-446
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Initial changes of hepatic glycogen granules and glycogen phosphorylase a after exposure to 7,12-dimethylbenz[a]anthracene in rats.2003
Author(s)
Muto, T, Takasaki, S, Takahashi, T, Hano, H, Kanai, Y, Wakui, S, Endou, H, Furusato, M
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Journal Title
J.Toxicol.Pathol. 16
Pages: 153-160
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identification of a novel voltage-driven organic anion transporter present at apical membrane of renal proximal tubule.2003
Author(s)
Jutabha P, Kanai Y, Hosoyamada M, Chairoungdua A, Kim do K, Iribe Y, Babu E, Kim JY, Anzai N, Chatsudthipong V, Endou H
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Journal Title
J Biol Chem 278(30)
Pages: 27930-27938
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters.2003
Author(s)
Babu E, Kanai Y, Chairoungdua A, Kim do K, Iribe Y, Tangtrongsup S, Jutabha P, Li Y, Ahmed N, Sakamoto S, Anzai N, Nagamori S, Endou H
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Journal Title
J Biol Chem 278(44)
Pages: 43838-43845
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Time course of expression of 7,12-dimethylbenz[a]anthracene-induced CYP1A1 and CYP1B1 mRNA and protein in rat liver.2003
Author(s)
Muto, T, Watanabe, T, Moto, M, Okamura, M, Kashida, Y, Kanai, Y, Mitsumori, K, Endou, H
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Journal Title
J.Toxicol.Pathol. 16
Pages: 287-290
Description
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[Journal Article] Identification of a novel Na+-independent acidic amino acid transporter with structural similarity to the member of a heterodimeric amino acid transporter family associated with unknown heavy chains.2002
Author(s)
Matsuo H, Kanai Y, Kim JY, Chairoungdua A, Kim do K, Inatomi J, Shigeta Y, Ishimine H, Chaekuntode S, Tachampa K, Choi HW, Babu E, Fukuda J, Endou H
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Journal Title
J Biol Chem 277(23)
Pages: 21017-21026
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Molecular identification of a renal urate anion exchanger that regulates blood urate levels.2002
Author(s)
Enomoto A, Kimura H, Chairoungdua A, Shigeta Y, Jutabha P, Cha SH, Hosoyamada M, Takeda M, Sekine T, Igarashi T, Matsuo H, Kikuchi Y, Oda T, Ichida K, Hosoya T, Shimokata K, Niwa T, Kanai Y, Endou H
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Journal Title
Nature 417(6887)
Pages: 447-452
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Molecular identification of a novel carnitine transporter specific to human testis. Insights into the mechanism of carnitine recognition.2002
Author(s)
Enomoto A, Wempe MF, Tsuchida H, Shin HJ, Cha SH, Anzai N, Goto A, Sakamoto A, Niwa T, Kanai Y, Anders MW, Endou H
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Journal Title
J Biol Chem 277(39)
Pages: 36262-36271
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] M6a acts as a nerve growth factor-gated Ca(2+) channel in neuronal differentiation.2002
Author(s)
Mukobata, S, Hibino, T, Sugiyama, A, Urano, Y, Inatomi, A, Kanai, Y, Endo, H, Tashiro F
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Journal Title
Biochem.Biophys.Res.Commun. 297
Pages: 722-728
Description
「研究成果報告書概要(欧文)」より
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