The H(+)-dependent reduced folate carrier 1 of humans and the sodium-dependent methotrexate carrier-1 of the rat are orthologs.
Previously, two different carrier systems for uptake of reduced folates and the antifolate methotrexate (Mtx) were described: the pH-dependent folate sensitive reduced folate carrier 1 (RFC1) from human, hamster and mouse and a sodium-dependent and folate insensitive Mtx carrier-1 (MTX-1) from rat. It was found that all critical residues of the homologous amino acid sequence were identical. RFC1- as well as MTX-1-mediated uptake of a marker substrate into suitable human and rat cell lines increased with proton concentration, was sodium-dependent at neutral pH, and inhibited by folate at acidic pH. It is concluded that RFC1 and MTX-1 are orthologs.
Kneuer
Carsten
C
Institute of Pharmacology, Pharmacy and Toxicology, An den Tierkliniken 15, University of Leipzig, 04103 Leipzig, Germany.
Honscha
Walther
W
D000595:Amino Acid Sequence; D000818:Animals; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D006224:Cricetinae; D019793:Fluorescein / Q000737:chemistry / Q000378:metabolism; D005492:Folic Acid / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins; D008727:Methotrexate / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D051381:Rats; D058978:Reduced Folate Carrier Protein; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence
D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D015778:Minor Histocompatibility Antigens; D058978:Reduced Folate Carrier Protein; C120043:SLC19A2 protein, human; C043408:Slc19a1 protein, rat; C492292:Slc19a2 protein, mouse; D005492:Folic Acid; D012964:Sodium; D019793:Fluorescein; D008727:Methotrexate