Structure and function of ATA3, a new subtype of amino acid transport system A, primarily expressed in the liver and skeletal muscle.
To date, two different transporters that are capable of transporting alpha-(methylamino)isobutyric acid, the specific substrate for amino acid transport system A, have been cloned. These two transporters are known as ATA1 and ATA2. We have cloned a third transporter that is able to transport the system A-specific substrate. This new transporter, cloned from rat skeletal muscle and designated rATA3, consists of 547 amino acids and has a high degree of homology to rat ATA1 (47% identity) and rat ATA2 (57% identity). rATA3 mRNA is present only in the liver and skeletal muscle. When expressed in Xenopus laevis oocytes, rATA3 mediates the transport of alpha-[(14)C](methylamino)isobutyric acid and [(3)H]alanine. With the two-microelectrode voltage clamp technique, we have shown that exposure of rATA3-expressing oocytes to neutral, short-chain aliphatic amino acids induces inward currents. The amino acid-induced current is Na(+)-dependent and pH-dependent. Analysis of the currents with alanine as the substrate has shown that the K(0. 5) for alanine (i.e., concentration of the amino acid yielding half-maximal current) is 4.2+/-0.1 mM and that the Na(+):alanine stoichiometry is 1:1.
Sugawara
M
M
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912-2100, USA.
Nakanishi
T
T
Fei
Y J
YJ
Martindale
R G
RG
Ganapathy
M E
ME
Leibach
F H
FH
Ganapathy
V
V
D000409:Alanine / Q000378:metabolism; D000595:Amino Acid Sequence; D026905:Amino Acid Transport Systems; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000096:biosynthesis; D004594:Electrophysiology; D015723:Gene Library; D008099:Liver / Q000378:metabolism*; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014982:Xenopus laevis; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000378:metabolism
D026905:Amino Acid Transport Systems; D002352:Carrier Proteins; D018076:DNA, Complementary; D015091:beta-Alanine; C012924:2,2-dimethyl-beta-alanine; D000409:Alanine