Molecular cloning and functional characterization of a GABA/betaine transporter from human kidney.
The human homologue of the canine GABA/betaine transporter (BGT-1) was isolated from a kidney inner medulla cDNA library. The coding sequence predicts a 614 amino acids protein with the typical features of neurotransmitter transporter family. The gene maps to chromosome 12p13 and, in addition to kidney, is also expressed in brain, liver, heart, skeletal muscle, and placenta. Functional studies reveal a Km = 20 microM for GABA transport and a coupling to Na+ and Cl- with a stoichiometry 3 Na+:2 Cl-:1 GABA. At 500 microM the GABA transport was inhibited by various compounds with the following potency order: quinidine > verapamil > phloretin > betaine.
Rasola
A
A
Laboratorio di Genetica Molecolare, Istituto G. Gaslini, Genova, Italy.
Galietta
L J
LJ
Barone
V
V
Romeo
G
G
Bagnasco
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001622:Betaine / Q000378:metabolism / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D003001:Cloning, Molecular; D004285:Dogs; D050485:GABA Plasma Membrane Transport Proteins; D006801:Humans; D007679:Kidney Medulla / Q000737:chemistry*; D007700:Kinetics; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D027361:Organic Anion Transporters; D010693:Phloretin / Q000494:pharmacology; D011802:Quinidine / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002352:Carrier Proteins; D002712:Chlorides; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; C072207:betaine plasma membrane transport proteins; D001622:Betaine; D005680:gamma-Aminobutyric Acid; D012964:Sodium; D014700:Verapamil; D011802:Quinidine; D010693:Phloretin