title: Genetic variant Arg57His in human H+/peptide cotransporter 2 causes a complete loss of transport function.
abstract: We evaluated the functional consequences of genetic variations in human H(+)/peptide cotransporter 2 (hPEPT2, SLC15A2) resulting in the amino acid changes Arg57His (R57H) and Pro409Ser (P409S). The transport activity of variant R57H was completely abolished, whereas that of variant P409S was comparable with that of wild-type hPEPT2 at pH 5.0-8.0. R57H variant protein was detected in the crude membranes of transiently expressed HEK293 cells by Western blot analysis. The expression of the R57H variant at the plasma membrane was confirmed by indirect immunofluorescence in Xenopus oocytes, suggesting that the loss of transport function of hPEPT2 R57H was not due to a change in membrane protein expression. This is the first demonstration of a functional impairment of the SLC15A family induced by a single nucleotide polymorphism.
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Terada
authors.forename: Megumi
authors.initials: M
authors.lastname: Irie
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okuda
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Inui
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001120:Arginine / Q000235:genetics; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D004151:Dipeptides / Q000378:metabolism; D006639:Histidine / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009865:Oocytes / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D027981:Symporters / Q000235:genetics* / Q000378:metabolism*; D014981:Xenopus
chemical_list: D004151:Dipeptides; D027981:Symporters; C093694:hydrogen-coupled oligopeptide transporter PepT2; C004194:glycylsarcosine; D006639:Histidine; D001120:Arginine