ID:LAT1_HUMAN DESCRIPTION: RecName: Full=Large neutral amino acids transporter small subunit 1; AltName: Full=4F2 light chain; Short=4F2 LC; Short=4F2LC; AltName: Full=CD98 light chain; AltName: Full=Integral membrane protein E16; AltName: Full=L-type amino acid transporter 1; Short=hLAT1; AltName: Full=Solute carrier family 7 member 5; AltName: Full=y+ system cationic amino acid transporter; FUNCTION: Sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan, when associated with SLC3A2/4F2hc. Involved in cellular amino acid uptake. Acts as an amino acid exchanger. Involved in the transport of L-DOPA across the blood- brain barrier, and that of thyroid hormones triiodothyronine (T3) and thyroxine (T4) across the cell membrane in tissues such as placenta. Plays a role in neuronal cell proliferation (neurogenesis) in brain. Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity. Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L- nitrosocysteine (L-CNSO) across the transmembrane. May play an important role in high-grade gliomas. Mediates blood-to-retina L- leucine transport across the inner blood-retinal barrier which in turn may play a key role in maintaining large neutral amino acids as well as neurotransmitters in the neural retina. Acts as the major transporter of tyrosine in fibroblasts. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=7.9 uM for T4 (in the presence of choline chloride); KM=0.8 uM for T3 (in the presence of choline chloride); KM=12.5 uM for reverse triiodothyronine (rT3) (in the presence of choline chloride); KM=7.9 uM for 3,3'-diiodothyronine (in the presence of choline chloride); KM=46 uM for leucine (in the presence of choline chloride); KM=19 uM for tryptophan (in the presence of choline chloride); KM=32 uM for L-leucine; KM=10 mM for L-alanine; KM=2.2 mM for L-glutamine; KM=35 uM for L-histidine; KM=740 uM for L-phenylalanine; KM=98 uM for MeHg-L-cysteine; KM=99 uM for methionine; KM=55.2 uM for phenylalanine (in T24 human bladder carcinoma cells); KM=60.4 uM for tyrosine (in T24 human bladder carcinoma cells); KM=16.4 uM for tyrosine (in human fibroblasts); KM=138 uM for Dopa (in T24 human bladder carcinoma cells); KM=96.5 uM for 3-O-methyldopa (in T24 human bladder carcinoma cells); KM=153 uM for alpha-methyltyrosine (in T24 human bladder carcinoma cells); KM=216 uM for alpha-methyldopa (in T24 human bladder carcinoma cells); KM=191 uM for gabapentin (in T24 human bladder carcinoma cells); KM=7.3 uM for triiodothyronine (in T24 human bladder carcinoma cells); KM=162 uM for thyroxine (in T24 human bladder carcinoma cells); KM=75.3 uM for melphanan (in T24 human bladder carcinoma cells); KM=156 uM for BCH (in T24 human bladder carcinoma cells); SUBUNIT: Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc. SUBCELLULAR LOCATION: Cytoplasm, cytosol. Apical cell membrane; Multi-pass membrane protein. Note=Located to the plasma membrane by SLC3A2/4F2hc. Localized to the apical membrane of placental syncytiophoblastic cells. Expressed in both luminal and abluminal membranes of brain capillary endothelial cells (By similarity). TISSUE SPECIFICITY: Expressed abundantly in adult lung, liver, brain, skeletal muscle, placenta, bone marrow, testis, resting lymphocytes and monocytes, and in fetal liver. Weaker expression in thymus, cornea, retina, peripheral leukocytes, spleen, kidney, colon and lymph node. During gestation, expression in the placenta was significantly stronger at full-term than at the mid-trimester stage. Also expressed in all human tumor cell lines tested and in the astrocytic process of primary astrocytic gliomas. Expressed in retinal endothelial cells and in the intestinal epithelial cell line Caco-2. INDUCTION: Expression induced in quiescent peripheral blood lymphocytes after treatment with phorbol myristate acetate (PMA) and phytohemagglutinin (PHA). Expression and the uptake of leucine is stimulated in mononuclear, cytotrophoblast-like choriocarcinoma cells by combined treatment with PMA and calcium ionophore. MISCELLANEOUS: The uptake of leucine, tyrosine and tryptophan is inhibited by the different iodothyronines, in particular T3. Leucine transport is also inhibited by small zwitterionic amino acids (i.e. glycine, alanine, serine, threonine and cysteine) and by glutamine and asparginine. The uptake of T3 is almost completely blocked by coincubation with leucine, tryptophan, tyrosine, and phenylalanine, or 2-amino-bicyclo-(2,2,1)-heptane-2- carboxylate (BCH). Methionine uptake was inhibited by the L-system substrates L-leucine, BCH, L-cysteine and by the MeHg-L-cysteine complex and structurally related S-ethyl-L-cysteine. MeHg-L- cysteine uptake is inhibited by L-methionine, L-leucine, BCH and S-ethyl-L-cysteine. L-leucine uptake was inhibited by L-CNSO. Tyrosine uptake in fibroblasts was inhibited by D-methionine, and methyl-aminoisobutyric acid (MeAIB). SIMILARITY: Belongs to the amino acid-polyamine-organocation (APC) superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q01650
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0003333 amino acid transmembrane transport GO:0006520 cellular amino acid metabolic process GO:0006865 amino acid transport GO:0007275 multicellular organism development GO:0007399 nervous system development GO:0015804 neutral amino acid transport GO:0015807 L-amino acid transport GO:0030154 cell differentiation GO:0050900 leukocyte migration GO:0055085 transmembrane transport GO:1902475 L-alpha-amino acid transmembrane transport