solute carrier family 7 member 8; large neutral amino acids transporter small subunit 2; L-type amino acid transporter 2; hLAT2 (SLC7A8, LAT2)
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Function
- Na+-independent, high-affinity transport of small & large neutral amino acids such as alanine, serine, threonine, cysteine, phenylalanine, tyrosine, leucine, arginine & tryptophan, when associated with SLC3A2/4F2hc
- acts as an amino acid exchanger
- has higher affinity for L-phenylalanine than LAT1 but lower affinity for glutamine & serine
- L-alanine is transported at physiological concentrations
- role in basolateral reabsorption of neutral amino acids
- role in uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, & hence plays a role in metal ion homeostasis & toxicity
- role in cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane
- role in reabsorption of neutral amino acids from epithelial cells to the bloodstream in the kidney
- disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc
- KM=221 uM for L-leucine
- KM=64 uM for MeHg-L-cysteine
- KM=161 uM for methionine
- KM=978 uM for L-alanine
- KM=89.35 uM for L-phenylalanine
- KM=57.3 uM for L-tryptophan
- KM=48.8 uM for L-tyrosine
Structure
- belongs to the amino acid-polyamine-organocation (APC) superfamily, L-type amino acid transporter (LAT) (TC 2.A.3.8) family
Compartment
- cytoplasm, basolateral cell membrane
- localized to the cytoplasm when expressed alone but when coexpressed with SLC3A2/4F2hc, is localized to the plasma membrane
- colocalized with SLC3A2/4F2hc at the basolateral membrane of renal cortex proximal tubules & small intestine villous epithelia
Expression
- highest expression is in kidney
- lesser expression in placenta & brain > liver, prostate, testis, ovary, lymph node, thymus, spleen, skeletal muscle & heart
- also expressed in fetal liver as well as in the retinal pigment epithelial cell line ARPE-19 & the intestinal epithelial cell line Caco-2
- activity in polarized intestinal cells is regulated by the association between SLC3A2/4F2 (in the SLC3A2/4F2-LAT2 heterodimer) & ICAM1
Notes
- L-leucine transport activity is inhibited by small zwitterionic amino acids (i.e. glycine, alanine, serine, threonine, asparginine, glutamine, methionine, leucine, isoleucine, valine, phenylalanine, tyrosine, tryptophan, histidine & cysteine) & by glutamine & asparginine
- methionine uptake is inhibited by the L-system substrates L-leucine, 2-amino-bicyclo-(2,2,1)-heptane-2-carboxylate (BCH), L-cysteine & by the MeHg-L-cysteine complex & structurally related S-ethyl-L-cysteine
- MeHg-L-cysteine uptake is inhibited by L-methionine, L-leucine, BCH & S-ethyl-L-cysteine
- L-leucine uptake is inhibited by L-CNSO