solute carrier family 7 member 6 (y(+)L amino acid transporter 2, y(+)L-type amino acid transporter 2, y+LAT-2, Y+LAT2, cationic amino acid transporter, y+ system, SLC7A6, KIAA0245)
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Function
- role in the Na+-independent uptake of dibasic amino acids & Na+-dependent uptake of some neutral amino acids
- requires co-expression with SLC3A2/4F2hc to mediate the uptake of arginine, leucine & glutamine
- also acts as an arginine/glutamine exchanger, following an antiport mechanism for amino acid transport, influencing arginine release in exchange for extracellular amino acids
- plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine
- involved in the transport of L-arginine in monocytes
- reduces uptake of ornithine in retinal pigment epithelial cells
- disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc
- KM=295 uM for glutamine (in the presence of NaCl)
- KM=236 uM for leucine (in the presence of NaCl)
- KM=120 uM for arginine (in the presence of NaCl)
- KM=138 uM for arginine (in the absence of NaCl)
Inhibition:
- arginine transport is strongly inhibited by lysine, glutamate, leucine, glutamine, methionine & histidine, in the presence of Na+
- also inhibited by protein kinase C (PKC) & treatment with phorbol-12-myristate-13-acetate (PMA)
- mutual inhibition is observed when leucine or glutamine is used as substrate
- inhibition of arginine & leucine uptake also occurs when SLC3A2/4F2hc is either truncated at its C-terminus or mutated at critical residues within the terminal 15 amino acids
Structure
- belongs to the amino acid-polyamine-organocation (APC) superfamily, L-type amino acid transporter (LAT) (TC 2.A.3.8) family
Compartment
Expression
- expressed in normal fibroblasts & those from LPI patients
- also expressed in HUVECs, monocytes, RPE cells, & various carcinoma cell lines