Evidence for the transport of neutral as well as cationic amino acids by ATA3, a novel and liver-specific subtype of amino acid transport system A.
We report here on the cloning and functional characterization of the third subtype of amino acid transport system A, designated ATA3 (amino acid transporter A3), from a human liver cell line. This transporter consists of 547 amino acids and is structurally related to the members of the glutamine transporter family. The human ATA3 (hATA3) exhibits 88% identity in amino acid sequence with rat ATA3. The gene coding for hATA3 contains 16 exons and is located on human chromosome 12q13. It is expressed almost exclusively in the liver. hATA3 mediates the transport of neutral amino acids including alpha-(methylamino)isobutyric acid (MeAIB), the model substrate for system A, in a Na(+)-coupled manner and the transport of cationic amino acids in a Na(+)-independent manner. The affinity of hATA3 for cationic amino acids is higher than for neutral amino acids. The transport function of hATA3 is thus similar to that of system y(+)L. The ability of hATA3 to transport cationic amino acids with high affinity is unique among the members of the glutamine transporter family. hATA1 and hATA2, the other two known members of the system A subfamily, show little affinity toward cationic amino acids. hATA3 also differs from hATA1 and hATA2 in exhibiting low affinity for MeAIB. Since liver does not express any of the previously known high-affinity cationic amino acid transporters, ATA3 is likely to provide the major route for the uptake of arginine in this tissue.
Hatanaka
T
T
Huang
W
W
Ling
R
R
Prasad
P D
PD
Sugawara
M
M
Leibach
F H
FH
Ganapathy
V
V
D026905:Amino Acid Transport Systems; D021542:Amino Acids, Neutral / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism; D001692:Biological Transport; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002881:Chromosomes, Human, Pair 12; D004847:Epithelial Cells / Q000378:metabolism; D005091:Exons; D005998:Glycine / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007438:Introns; D008099:Liver / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013379:Substrate Specificity; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000378:metabolism
D026905:Amino Acid Transport Systems; D021542:Amino Acids, Neutral; D002352:Carrier Proteins; D012333:RNA, Messenger; D015091:beta-Alanine; C012924:2,2-dimethyl-beta-alanine; D001120:Arginine; D005998:Glycine