ID LAT1_HUMAN Reviewed; 507 AA. AC Q01650; Q8IV97; Q9UBN8; Q9UP15; Q9UQC0; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 24-JAN-2001, sequence version 2. DT 27-MAR-2024, entry version 222. DE RecName: Full=Large neutral amino acids transporter small subunit 1; DE AltName: Full=4F2 light chain; DE Short=4F2 LC; DE Short=4F2LC; DE AltName: Full=CD98 light chain; DE AltName: Full=Integral membrane protein E16 {ECO:0000303|PubMed:9751058}; DE Short=E16 {ECO:0000303|PubMed:9751058}; DE AltName: Full=L-type amino acid transporter 1 {ECO:0000303|PubMed:11557028}; DE Short=hLAT1 {ECO:0000303|PubMed:11557028}; DE AltName: Full=Solute carrier family 7 member 5; DE AltName: Full=y+ system cationic amino acid transporter; GN Name=SLC7A5; GN Synonyms=CD98LC, LAT1 {ECO:0000303|PubMed:10049700, GN ECO:0000303|PubMed:11557028}, MPE16; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, INTERACTION WITH SLC3A2, RP SUBCELLULAR LOCATION, VARIANT LYS-230, AND TRANSPORTER ACTIVITY. RX PubMed=9751058; DOI=10.1038/26246; RA Mastroberardino L., Spindler B., Pfeiffer R., Skelly P.J., Loffing J., RA Shoemaker C.B., Verrey F.; RT "Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a RT permease family."; RL Nature 395:288-291(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, INTERACTION WITH SLC3A2, RP TISSUE SPECIFICITY, AND TRANSPORTER ACTIVITY. RC TISSUE=Placenta; RX PubMed=10049700; DOI=10.1006/bbrc.1999.0206; RA Prasad P.D., Wang H., Huang W., Kekuda R., Rajan D.P., Leibach F.H., RA Ganapathy V.; RT "Human LAT1, a subunit of system L amino acid transporter: molecular RT cloning and transport function."; RL Biochem. Biophys. Res. Commun. 255:283-288(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND TISSUE RP SPECIFICITY. RX PubMed=10072483; RA Tsurudome M., Ito M., Takebayashi S., Okumura K., Nishio M., Kawano M., RA Kusagawa S., Komada H., Ito Y.; RT "Primary structure of the light chain of fusion regulatory protein- RT 1/CD98/4F2 predicts a protein with multiple transmembrane domains that is RT almost identical to the amino acid transporter E16."; RL J. Immunol. 162:2462-2466(1999). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, TRANSPORTER ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RC TISSUE=Ovary; RX PubMed=11557028; DOI=10.1016/s0005-2736(01)00384-4; RA Yanagida O., Kanai Y., Chairoungdua A., Kim D.K., Segawa H., Nii T., RA Cha S.H., Matsuo H., Fukushima J., Fukasawa Y., Tani Y., Taketani Y., RA Uchino H., Kim J.Y., Inatomi J., Okayasu I., Miyamoto K., Takeda E., RA Goya T., Endou H.; RT "Human L-type amino acid transporter 1 (LAT1): characterization of function RT and expression in tumor cell lines."; RL Biochim. Biophys. Acta 1514:291-302(2001). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Minato N., Iwai K., Takizawa C., Nakamura E.; RT "Human 4F2 light chain: amino acid transporter."; RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-223. RC TISSUE=Liver, and Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 181-507, TISSUE SPECIFICITY, AND INDUCTION. RC TISSUE=Peripheral blood lymphocyte; RX PubMed=1597461; DOI=10.1016/s0021-9258(19)49906-7; RA Gaugitsch H.W., Prieschl E.E., Kalthoff F., Huber N.E., Baumruker T.; RT "A novel transiently expressed, integral membrane protein linked to cell RT activation. Molecular cloning via the rapid degradation signal AUUUA."; RL J. Biol. Chem. 267:11267-11273(1992). RN [8] RP FUNCTION, SUBUNIT, AND TRANSPORTER ACTIVITY. RX PubMed=10574970; DOI=10.1074/jbc.274.49.34948; RA Rossier G., Meier C., Bauch C., Summa V., Sordat B., Verrey F., Kuehn L.C.; RT "LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of RT kidney and intestine."; RL J. Biol. Chem. 274:34948-34954(1999). RN [9] RP SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=11389679; DOI=10.1042/0264-6021:3560719; RA Ritchie J.W.A., Taylor P.M.; RT "Role of the System L permease LAT1 in amino acid and iodothyronine RT transport in placenta."; RL Biochem. J. 356:719-725(2001). RN [10] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, ACTIVITY REGULATION, AND RP TRANSPORTER ACTIVITY. RX PubMed=11564694; DOI=10.1210/endo.142.10.8418; RA Friesema E.C.H., Docter R., Moerings E.P.C.M., Verrey F., Krenning E.P., RA Hennemann G., Visser T.J.; RT "Thyroid hormone transport by the heterodimeric human system L amino acid RT transporter."; RL Endocrinology 142:4339-4348(2001). RN [11] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION. RX PubMed=11742812; DOI=10.1152/ajpcell.2002.282.1.c196; RA Okamoto Y., Sakata M., Ogura K., Yamamoto T., Yamaguchi M., Tasaka K., RA Kurachi H., Tsurudome M., Murata Y.; RT "Expression and regulation of 4F2hc and hLAT1 in human trophoblasts."; RL Am. J. Physiol. 282:C196-C204(2002). RN [12] RP FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, TRANSPORTER ACTIVITY, AND RP ACTIVITY REGULATION. RX PubMed=12117417; DOI=10.1042/bj20020841; RA Simmons-Willis T.A., Koh A.S., Clarkson T.W., Ballatori N.; RT "Transport of a neurotoxicant by molecular mimicry: the methylmercury-L- RT cysteine complex is a substrate for human L-type large neutral amino acid RT transporter (LAT) 1 and LAT2."; RL Biochem. J. 367:239-246(2002). RN [13] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, RP ACTIVITY REGULATION, AND TRANSPORTER ACTIVITY. RX PubMed=12225859; DOI=10.1016/s0005-2736(02)00516-3; RA Kim D.K., Kanai Y., Choi H.W., Tangtrongsup S., Chairoungdua A., Babu E., RA Tachampa K., Anzai N., Iribe Y., Endou H.; RT "Characterization of the system L amino acid transporter in T24 human RT bladder carcinoma cells."; RL Biochim. Biophys. Acta 1565:112-121(2002). RN [14] RP TISSUE SPECIFICITY. RX PubMed=12824232; DOI=10.1167/iovs.02-0907; RA Jain-Vakkalagadda B., Dey S., Pal D., Mitra A.K.; RT "Identification and functional characterization of a Na+-independent large RT neutral amino acid transporter, LAT1, in human and rabbit cornea."; RL Invest. Ophthalmol. Vis. Sci. 44:2919-2927(2003). RN [15] RP TISSUE SPECIFICITY. RX PubMed=16027961; DOI=10.1007/s00726-005-0221-x; RA Fraga S., Pinho M.J., Soares-da-Silva P.; RT "Expression of LAT1 and LAT2 amino acid transporters in human and rat RT intestinal epithelial cells."; RL Amino Acids 29:229-233(2005). RN [16] RP FUNCTION, SUBUNIT, TRANSPORTER ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=15769744; DOI=10.1074/jbc.m413164200; RA Li S., Whorton A.R.; RT "Identification of stereoselective transporters for S-nitroso-L-cysteine: RT role of LAT1 and LAT2 in biological activity of S-nitrosothiols."; RL J. Biol. Chem. 280:20102-20110(2005). RN [17] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=16496379; DOI=10.1002/ijc.21866; RA Nawashiro H., Otani N., Shinomiya N., Fukui S., Ooigawa H., Shima K., RA Matsuo H., Kanai Y., Endou H.; RT "L-type amino acid transporter 1 as a potential molecular target in human RT astrocytic tumors."; RL Int. J. Cancer 119:484-492(2006). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [19] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TRANSPORTER ACTIVITY, AND ACTIVITY RP REGULATION. RX PubMed=18262359; DOI=10.1016/j.neulet.2008.01.028; RA Vumma R., Wiesel F.A., Flyckt L., Bjerkenstedt L., Venizelos N.; RT "Functional characterization of tyrosine transport in fibroblast cells from RT healthy controls."; RL Neurosci. Lett. 434:56-60(2008). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31 AND THR-45, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [23] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-31; SER-35 AND THR-45, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [26] RP INTERACTION WITH LAPTM4B AND SLC3A2, FUNCTION, SUBCELLULAR LOCATION, RP SUBUNIT, AND TRANSPORTER ACTIVITY. RX PubMed=25998567; DOI=10.1038/ncomms8250; RA Milkereit R., Persaud A., Vanoaica L., Guetg A., Verrey F., Rotin D.; RT "LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes RT mTORC1 activation."; RL Nat. Commun. 6:7250-7250(2015). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [28] RP FUNCTION (MICROBIAL INFECTION), AND INDUCTION BY HCV (MICROBIAL INFECTION). RX PubMed=30341327; DOI=10.1038/s41598-018-33861-6; RA Nguyen N.N.T., Lim Y.S., Nguyen L.P., Tran S.C., Luong T.T.D., RA Nguyen T.T.T., Pham H.T., Mai H.N., Choi J.W., Han S.S., Hwang S.B.; RT "Hepatitis C Virus Modulates Solute carrier family 3 member 2 for Viral RT Propagation."; RL Sci. Rep. 8:15486-15486(2018). RN [29] {ECO:0007744|PDB:6IRS, ECO:0007744|PDB:6IRT} RP STRUCTURE BY ELECTRON MICROSCOPY (3.30 ANGSTROMS) OF 2-507 IN COMPLEX WITH RP SLC3A2, FUNCTION, SUBUNIT, TOPOLOGY, DISULFIDE BOND, MUTAGENESIS OF RP TYR-117; ALA-246; PHE-252; TRP-257; ASN-258; TYR-259; GLU-303; PRO-375 AND RP 483-LYS--THR-507, AND TRANSPORTER ACTIVITY. RX PubMed=30867591; DOI=10.1038/s41586-019-1011-z; RA Yan R., Zhao X., Lei J., Zhou Q.; RT "Structure of the human LAT1-4F2hc heteromeric amino acid transporter RT complex."; RL Nature 568:127-130(2019). CC -!- FUNCTION: The heterodimer with SLC3A2 functions as a sodium- CC independent, high-affinity transporter that mediates uptake of large CC neutral amino acids such as phenylalanine, tyrosine, leucine, CC histidine, methionine, tryptophan, valine, isoleucine and alanine CC (PubMed:9751058, PubMed:10049700, PubMed:11557028, PubMed:10574970, CC PubMed:11564694, PubMed:12117417, PubMed:12225859, PubMed:25998567, CC PubMed:30867591, PubMed:18262359, PubMed:15769744). The heterodimer CC with SLC3A2 mediates the uptake of L-DOPA (By similarity). Functions as CC an amino acid exchanger (PubMed:11557028, PubMed:12117417, CC PubMed:12225859, PubMed:30867591). May play a role in the transport of CC L-DOPA across the blood-brain barrier (By similarity). May act as the CC major transporter of tyrosine in fibroblasts (Probable). May mediate CC blood-to-retina L-leucine transport across the inner blood-retinal CC barrier (By similarity).Can mediate the transport of thyroid hormones CC diiodothyronine (T2), triiodothyronine (T3) and thyroxine (T4) across CC the cell membrane (PubMed:11564694). When associated with LAPTM4B, the CC heterodimer formed by SLC3A2 and SLC7A5 is recruited to lysosomes to CC promote leucine uptake into these organelles, and thereby mediates CC mTORC1 activation (PubMed:25998567). Involved in the uptake of toxic CC methylmercury (MeHg) when administered as the L-cysteine or D,L- CC homocysteine complexes (PubMed:12117417). Involved in the cellular CC activity of small molecular weight nitrosothiols, via the CC stereoselective transport of L-nitrosocysteine (L-CNSO) across the CC membrane (PubMed:15769744). {ECO:0000250|UniProtKB:Q63016, CC ECO:0000250|UniProtKB:Q9Z127, ECO:0000269|PubMed:10049700, CC ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11557028, CC ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:12117417, CC ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:15769744, CC ECO:0000269|PubMed:18262359, ECO:0000269|PubMed:25998567, CC ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:9751058, CC ECO:0000305|PubMed:18262359}. CC -!- FUNCTION: (Microbial infection) In case of hepatitis C virus/HCV CC infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in CC HCV propagation by facilitating viral entry into host cell and CC increasing L-leucine uptake-mediated mTORC1 signaling activation, CC thereby contributing to HCV-mediated pathogenesis. CC {ECO:0000269|PubMed:30341327}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-phenylalanine(in) = L-phenylalanine(out); CC Xref=Rhea:RHEA:27950, ChEBI:CHEBI:58095; CC Evidence={ECO:0000269|PubMed:10049700, ECO:0000269|PubMed:10574970, CC ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, CC ECO:0000269|PubMed:9751058}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:27952; CC Evidence={ECO:0000305|PubMed:10049700}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-tryptophan(in) = L-tryptophan(out); Xref=Rhea:RHEA:70947, CC ChEBI:CHEBI:57912; Evidence={ECO:0000269|PubMed:10049700, CC ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11557028, CC ECO:0000269|PubMed:11564694}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70949; CC Evidence={ECO:0000305|PubMed:10049700}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-histidine(out) = L-histidine(in); Xref=Rhea:RHEA:72807, CC ChEBI:CHEBI:57595; Evidence={ECO:0000269|PubMed:10049700, CC ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11557028, CC ECO:0000269|PubMed:9751058}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-leucine(in) = L-leucine(out); Xref=Rhea:RHEA:73011, CC ChEBI:CHEBI:57427; Evidence={ECO:0000269|PubMed:10049700, CC ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11557028, CC ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:12225859, CC ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:25998567, CC ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:9751058}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:73013; CC Evidence={ECO:0000305|PubMed:10049700}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-isoleucine(in) = L-isoleucine(out); Xref=Rhea:RHEA:70943, CC ChEBI:CHEBI:58045; Evidence={ECO:0000269|PubMed:11557028}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70945; CC Evidence={ECO:0000305|PubMed:11557028}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-valine(in) = L-valine(out); Xref=Rhea:RHEA:29703, CC ChEBI:CHEBI:57762; Evidence={ECO:0000269|PubMed:11557028}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:29705; CC Evidence={ECO:0000305|PubMed:11557028}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-tyrosine(in) = L-tyrosine(out); Xref=Rhea:RHEA:68572, CC ChEBI:CHEBI:58315; Evidence={ECO:0000269|PubMed:11557028, CC ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:18262359}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68574; CC Evidence={ECO:0000305|PubMed:11557028}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-methionine(in) = L-methionine(out); Xref=Rhea:RHEA:70939, CC ChEBI:CHEBI:57844; Evidence={ECO:0000269|PubMed:11557028, CC ECO:0000269|PubMed:12117417}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70941; CC Evidence={ECO:0000305|PubMed:11557028}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-alanine(in) = L-alanine(out); Xref=Rhea:RHEA:70719, CC ChEBI:CHEBI:57972; Evidence={ECO:0000269|PubMed:18262359}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70721; CC Evidence={ECO:0000305|PubMed:18262359}; CC -!- CATALYTIC ACTIVITY: CC Reaction=3,3'-diiodo-L-thyronine(out) = 3,3'-diiodo-L-thyronine(in); CC Xref=Rhea:RHEA:71823, ChEBI:CHEBI:176514; CC Evidence={ECO:0000269|PubMed:11564694}; CC -!- CATALYTIC ACTIVITY: CC Reaction=3,3',5-triiodo-L-thyronine(out) = 3,3',5-triiodo-L- CC thyronine(in); Xref=Rhea:RHEA:71811, ChEBI:CHEBI:533015; CC Evidence={ECO:0000269|PubMed:11564694}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-thyroxine(out) = L-thyroxine(in); Xref=Rhea:RHEA:71819, CC ChEBI:CHEBI:58448; Evidence={ECO:0000269|PubMed:11564694}; CC -!- ACTIVITY REGULATION: The uptake of leucine, tyrosine and tryptophan is CC inhibited by the different iodothyronines, in particular T3 CC (PubMed:11564694). The uptake of T3 is almost completely blocked by CC coincubation with leucine, tryptophan, tyrosine, and phenylalanine, or CC 2-amino-bicyclo-(2,2,1)-heptane-2-carboxylate (BCH) (PubMed:11564694). CC Methionine uptake was inhibited by the L-system substrates L-leucine, CC BCH, L-cysteine and by the MeHg-L-cysteine complex and structurally CC related S-ethyl-L-cysteine (PubMed:12117417). MeHg-L-cysteine uptake is CC inhibited by L-methionine, L-leucine, BCH and S-ethyl-L-cysteine CC (PubMed:12117417). L-leucine transport is inhibited by phenylalanine, CC tyrosine, L-dopa, 3-O-methyldopa, a-methyltyrosine, a-methyldopa, CC gabapentin, triiodothyronine, thyroxine, melphalan and BCH CC (PubMed:12225859). L-leucine uptake was inhibited by L-CNSO CC (PubMed:15769744). Tyrosine uptake in fibroblasts was inhibited by D- CC methionine, and methyl-aminoisobutyric acid (MeAIB) (PubMed:18262359). CC {ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:12117417, CC ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:15769744, CC ECO:0000269|PubMed:18262359}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=7.9 uM for T4 (in the presence of choline chloride) CC {ECO:0000269|PubMed:11564694}; CC KM=0.8 uM for T3 (in the presence of choline chloride) CC {ECO:0000269|PubMed:11564694}; CC KM=12.5 uM for reverse triiodothyronine (rT3) (in the presence of CC choline chloride) {ECO:0000269|PubMed:11564694}; CC KM=7.9 uM for T2 (in the presence of choline chloride) CC {ECO:0000269|PubMed:11564694}; CC KM=46 uM for leucine (in the presence of choline chloride) CC {ECO:0000269|PubMed:11564694}; CC KM=19 uM for tryptophan (in the presence of choline chloride) CC {ECO:0000269|PubMed:11564694}; CC KM=19.7 uM for L-leucine {ECO:0000269|PubMed:11557028}; CC KM=25.1 uM for L-isoleucine {ECO:0000269|PubMed:11557028}; CC KM=14.2 uM for L-phenyalanine {ECO:0000269|PubMed:11557028}; CC KM=20.2 uM for L-methionine {ECO:0000269|PubMed:11557028}; CC KM=28.3 uM for L-tyrosine {ECO:0000269|PubMed:11557028}; CC KM=12.7 uM for L-histidine {ECO:0000269|PubMed:11557028}; CC KM=21.4 uM for L-tryptophan {ECO:0000269|PubMed:11557028}; CC KM=47.2 uM for L-valine {ECO:0000269|PubMed:11557028}; CC KM=98 uM for MeHg-L-cysteine {ECO:0000269|PubMed:12117417}; CC KM=99 uM for methionine {ECO:0000269|PubMed:12117417}; CC KM=100.5 uM for L-leucine {ECO:0000269|PubMed:12225859}; CC KM=16.4 uM for tyrosine (in human fibroblasts) CC {ECO:0000269|PubMed:18262359}; CC Vmax=23878 pmol/min/mg enzyme for L-leucine CC {ECO:0000269|PubMed:12225859}; CC Vmax=8.4 nmol/min/mg enzyme for tyrosine (in human fibroblasts) CC {ECO:0000269|PubMed:18262359}; CC Note=Km and Vmax values in PubMed:11564694 and PubMed:12225859 were CC determined for the heterodimer of SLC7A5/LAT1 and SLC3A2/4F2hc.; CC -!- SUBUNIT: Disulfide-linked heterodimer with the amino acid transport CC protein SLC3A2/4F2hc (PubMed:10049700, PubMed:10574970, CC PubMed:11389679, PubMed:11557028, PubMed:11564694, PubMed:12117417, CC PubMed:12225859, PubMed:15769744, PubMed:9751058, PubMed:25998567, CC PubMed:30867591). Interacts with LAPTM4B; this recruits the heterodimer CC formed by SLC3A2/4F2hc and SLC7A5 to lysosomes to promote leucine CC uptake into these organelles and is required for mTORC1 activation CC (PubMed:25998567). {ECO:0000269|PubMed:10049700, CC ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11389679, CC ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, CC ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:25998567, CC ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:9751058}. CC -!- INTERACTION: CC Q01650; P08195: SLC3A2; NbExp=2; IntAct=EBI-6138761, EBI-702356; CC Q01650; P08195-1: SLC3A2; NbExp=3; IntAct=EBI-6138761, EBI-11614088; CC -!- SUBCELLULAR LOCATION: Apical cell membrane CC {ECO:0000269|PubMed:11742812}; Multi-pass membrane protein CC {ECO:0000269|PubMed:30867591}. Cell membrane CC {ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:12225859, CC ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:9751058}; Multi-pass CC membrane protein {ECO:0000269|PubMed:30867591}. Lysosome membrane CC {ECO:0000269|PubMed:25998567}; Multi-pass membrane protein CC {ECO:0000305|PubMed:25998567}. Note=Located to the plasma membrane by CC SLC3A2/4F2hc (PubMed:9751058). Localized to the apical membrane of CC placental syncytiotrophoblastic cells (PubMed:11742812). Recruited to CC lysosomes by LAPTM4B (PubMed:25998567). {ECO:0000269|PubMed:11742812, CC ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:9751058}. CC -!- TISSUE SPECIFICITY: Detected in placenta, in the syncytiotrophoblast CC layer (at protein level) (PubMed:11389679). Expressed abundantly in CC adult lung, liver, brain, skeletal muscle, placenta, bone marrow, CC testis, resting lymphocytes and monocytes, and in fetal liver. Weaker CC expression in thymus, cornea, retina, peripheral leukocytes, spleen, CC kidney, colon and lymph node. During gestation, expression in the CC placenta was significantly stronger at full-term than at the mid- CC trimester stage. Also expressed in all human tumor cell lines tested CC and in the astrocytic process of primary astrocytic gliomas. Expressed CC in retinal endothelial cells and in the intestinal epithelial cell line CC Caco-2. {ECO:0000269|PubMed:10049700, ECO:0000269|PubMed:10072483, CC ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, CC ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:12824232, CC ECO:0000269|PubMed:1597461, ECO:0000269|PubMed:16027961, CC ECO:0000269|PubMed:16496379}. CC -!- INDUCTION: (Microbial infection) Up-regulation of the complex formed by CC SLC3A2 and SLC7A5/LAT1 upon hepatitis C virus/HCV infection. CC {ECO:0000269|PubMed:30341327}. CC -!- INDUCTION: Expression induced in quiescent peripheral blood lymphocytes CC after treatment with phorbol myristate acetate (PMA) and CC phytohemagglutinin (PHA). Expression and the uptake of leucine is CC stimulated in mononuclear, cytotrophoblast-like choriocarcinoma cells CC by combined treatment with PMA and calcium ionophore. CC {ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:1597461}. CC -!- SIMILARITY: Belongs to the amino acid-polyamine-organocation (APC) CC superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF077866; AAC61479.1; -; mRNA. DR EMBL; AF104032; AAD20464.1; -; mRNA. DR EMBL; AB018542; BAA33851.1; -; mRNA. DR EMBL; AB018009; BAA84648.1; -; mRNA. DR EMBL; AB017908; BAA75746.1; -; mRNA. DR EMBL; BC039692; AAH39692.1; -; mRNA. DR EMBL; BC042600; AAH42600.1; -; mRNA. DR EMBL; M80244; AAA35780.1; -; mRNA. DR CCDS; CCDS10964.1; -. DR PIR; JG0165; JG0165. DR RefSeq; NP_003477.4; NM_003486.6. DR PDB; 6IRS; EM; 3.30 A; B=2-507. DR PDB; 6IRT; EM; 3.50 A; B=2-507. DR PDB; 6JMQ; EM; 3.31 A; A=1-507. DR PDB; 7DSK; EM; 2.90 A; B=2-507. DR PDB; 7DSL; EM; 2.90 A; B=2-507. DR PDB; 7DSN; EM; 3.10 A; B=2-507. DR PDB; 7DSQ; EM; 3.40 A; B=2-507. DR PDBsum; 6IRS; -. DR PDBsum; 6IRT; -. DR PDBsum; 6JMQ; -. DR PDBsum; 7DSK; -. DR PDBsum; 7DSL; -. DR PDBsum; 7DSN; -. DR PDBsum; 7DSQ; -. DR AlphaFoldDB; Q01650; -. DR EMDB; EMD-30835; -. DR EMDB; EMD-30837; -. DR EMDB; EMD-30839; -. DR EMDB; EMD-30841; -. DR EMDB; EMD-4642; -. DR EMDB; EMD-9721; -. DR EMDB; EMD-9722; -. DR EMDB; EMD-9849; -. DR SMR; Q01650; -. DR BioGRID; 113801; 186. DR ComplexPortal; CPX-8185; LAT1-4F2 heteromeric amino acid transporter complex. DR IntAct; Q01650; 57. DR MINT; Q01650; -. DR STRING; 9606.ENSP00000261622; -. DR BindingDB; Q01650; -. DR ChEMBL; CHEMBL4459; -. DR DrugBank; DB01746; D-Leucine. DR DrugBank; DB02556; D-Phenylalanine. DR DrugBank; DB00509; Dextrothyroxine. DR DrugBank; DB00996; Gabapentin. DR DrugBank; DB00130; L-Glutamine. DR DrugBank; DB01235; Levodopa. DR DrugBank; DB00451; Levothyroxine. DR DrugBank; DB00279; Liothyronine. DR DrugBank; DB01042; Melphalan. DR DrugBank; DB00230; Pregabalin. DR DrugBank; DB02750; S-(Methylmercury)-L-Cysteine. DR DrugBank; DB09100; Thyroid, porcine. DR DrugCentral; Q01650; -. DR TCDB; 2.A.3.8.25; the amino acid-polyamine-organocation (apc) family. DR GlyGen; Q01650; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q01650; -. DR PhosphoSitePlus; Q01650; -. DR SwissPalm; Q01650; -. DR BioMuta; SLC7A5; -. DR DMDM; 12643412; -. DR EPD; Q01650; -. DR jPOST; Q01650; -. DR MassIVE; Q01650; -. DR MaxQB; Q01650; -. DR PaxDb; 9606-ENSP00000261622; -. DR PeptideAtlas; Q01650; -. DR ProteomicsDB; 57978; -. DR Pumba; Q01650; -. DR TopDownProteomics; Q01650; -. DR Antibodypedia; 17241; 451 antibodies from 39 providers. DR DNASU; 8140; -. DR Ensembl; ENST00000261622.5; ENSP00000261622.4; ENSG00000103257.9. DR GeneID; 8140; -. DR KEGG; hsa:8140; -. DR MANE-Select; ENST00000261622.5; ENSP00000261622.4; NM_003486.7; NP_003477.4. DR UCSC; uc002fkm.4; human. DR AGR; HGNC:11063; -. DR CTD; 8140; -. DR DisGeNET; 8140; -. DR GeneCards; SLC7A5; -. DR HGNC; HGNC:11063; SLC7A5. DR HPA; ENSG00000103257; Tissue enhanced (bone marrow, esophagus). DR MIM; 600182; gene. DR neXtProt; NX_Q01650; -. DR OpenTargets; ENSG00000103257; -. DR PharmGKB; PA35923; -. DR VEuPathDB; HostDB:ENSG00000103257; -. DR eggNOG; KOG1287; Eukaryota. DR GeneTree; ENSGT00940000155581; -. DR HOGENOM; CLU_007946_3_0_1; -. DR InParanoid; Q01650; -. DR OMA; WCQKVME; -. DR OrthoDB; 1103451at2759; -. DR PhylomeDB; Q01650; -. DR TreeFam; TF313355; -. DR BioCyc; MetaCyc:ENSG00000103257-MONOMER; -. DR PathwayCommons; Q01650; -. DR Reactome; R-HSA-210991; Basigin interactions. DR Reactome; R-HSA-352230; Amino acid transport across the plasma membrane. DR Reactome; R-HSA-71240; Tryptophan catabolism. DR SABIO-RK; Q01650; -. DR SignaLink; Q01650; -. DR BioGRID-ORCS; 8140; 293 hits in 1180 CRISPR screens. DR ChiTaRS; SLC7A5; human. DR GeneWiki; SLC7A5; -. DR GenomeRNAi; 8140; -. DR Pharos; Q01650; Tchem. DR PRO; PR:Q01650; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q01650; Protein. DR Bgee; ENSG00000103257; Expressed in pigmented layer of retina and 192 other cell types or tissues. DR ExpressionAtlas; Q01650; baseline and differential. DR GO; GO:1990184; C:amino acid transport complex; IDA:UniProtKB. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0009925; C:basal plasma membrane; ISS:ARUK-UCL. DR GO; GO:0016323; C:basolateral plasma membrane; ISS:ARUK-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0098591; C:external side of apical plasma membrane; ISS:ARUK-UCL. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0031528; C:microvillus membrane; IDA:ARUK-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0015171; F:amino acid transmembrane transporter activity; IDA:ARUK-UCL. DR GO; GO:0015297; F:antiporter activity; IDA:UniProtKB. DR GO; GO:0015173; F:aromatic amino acid transmembrane transporter activity; IGI:ARUK-UCL. DR GO; GO:0015179; F:L-amino acid transmembrane transporter activity; IBA:GO_Central. DR GO; GO:0015190; F:L-leucine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015196; F:L-tryptophan transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015175; F:neutral L-amino acid transmembrane transporter activity; IDA:ARUK-UCL. DR GO; GO:0042605; F:peptide antigen binding; ISS:UniProtKB. DR GO; GO:0015349; F:thyroid hormone transmembrane transporter activity; IDA:ARUK-UCL. DR GO; GO:0032328; P:alanine transport; IDA:UniProtKB. DR GO; GO:0089718; P:amino acid import across plasma membrane; IDA:ARUK-UCL. DR GO; GO:0003333; P:amino acid transmembrane transport; IBA:GO_Central. DR GO; GO:0042149; P:cellular response to glucose starvation; IEA:Ensembl. DR GO; GO:1903577; P:cellular response to L-arginine; IEA:Ensembl. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0015818; P:isoleucine transport; IDA:UniProtKB. DR GO; GO:1902024; P:L-histidine transport; IDA:UniProtKB. DR GO; GO:1903801; P:L-leucine import across plasma membrane; IDA:ARUK-UCL. DR GO; GO:1904556; P:L-tryptophan transmembrane transport; IDA:UniProtKB. DR GO; GO:0098713; P:leucine import across plasma membrane; IDA:ARUK-UCL. DR GO; GO:0015820; P:leucine transport; IDA:UniProtKB. DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl. DR GO; GO:0015821; P:methionine transport; IDA:UniProtKB. DR GO; GO:0010507; P:negative regulation of autophagy; IEA:Ensembl. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:ARUK-UCL. DR GO; GO:1905460; P:negative regulation of vascular associated smooth muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:0015804; P:neutral amino acid transport; IDA:UniProtKB. DR GO; GO:0015823; P:phenylalanine transport; IDA:UniProtKB. DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; TAS:ARUK-UCL. DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl. DR GO; GO:0032740; P:positive regulation of interleukin-17 production; IMP:ARUK-UCL. DR GO; GO:0032753; P:positive regulation of interleukin-4 production; IMP:ARUK-UCL. DR GO; GO:1905534; P:positive regulation of leucine import across plasma membrane; IEA:Ensembl. DR GO; GO:0032729; P:positive regulation of type II interferon production; IMP:ARUK-UCL. DR GO; GO:0015824; P:proline transport; IDA:UniProtKB. DR GO; GO:0055093; P:response to hyperoxia; IEA:Ensembl. DR GO; GO:0014850; P:response to muscle activity; IEA:Ensembl. DR GO; GO:0070327; P:thyroid hormone transport; IDA:UniProtKB. DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL. DR GO; GO:0015827; P:tryptophan transport; IDA:UniProtKB. DR GO; GO:0015828; P:tyrosine transport; IDA:UniProtKB. DR GO; GO:0015829; P:valine transport; IDA:UniProtKB. DR GO; GO:0042908; P:xenobiotic transport; IMP:ARUK-UCL. DR Gene3D; 1.20.1740.10; Amino acid/polyamine transporter I; 1. DR InterPro; IPR002293; AA/rel_permease1. DR InterPro; IPR004760; L_AA_transporter. DR NCBIfam; TIGR00911; 2A0308; 1. DR PANTHER; PTHR11785; AMINO ACID TRANSPORTER; 1. DR PANTHER; PTHR11785:SF315; LARGE NEUTRAL AMINO ACIDS TRANSPORTER SMALL SUBUNIT 1; 1. DR Pfam; PF13520; AA_permease_2; 1. DR PIRSF; PIRSF006060; AA_transporter; 1. DR Genevisible; Q01650; HS. PE 1: Evidence at protein level; KW 3D-structure; Amino-acid transport; Cell membrane; KW Direct protein sequencing; Disulfide bond; Isopeptide bond; Lysosome; KW Membrane; Phosphoprotein; Reference proteome; Transmembrane; KW Transmembrane helix; Transport; Ubl conjugation. FT CHAIN 1..507 FT /note="Large neutral amino acids transporter small subunit FT 1" FT /id="PRO_0000054270" FT TOPO_DOM 1..49 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 50..70 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30867591" FT TOPO_DOM 71..83 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 84..104 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30867591" FT TOPO_DOM 105..126 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 127..147 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30867591" FT TOPO_DOM 148..169 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 170..190 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30867591" FT TOPO_DOM 191..192 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 193..214 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30867591" FT TOPO_DOM 215..242 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 243..263 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30867591" FT TOPO_DOM 264..276 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 277..297 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30867591" FT TOPO_DOM 298..324 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 325..345 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30867591" FT TOPO_DOM 346..369 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 370..390 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30867591" FT TOPO_DOM 391..395 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 396..416 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30867591" FT TOPO_DOM 417..430 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 431..451 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30867591" FT TOPO_DOM 452..457 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 458..478 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30867591" FT TOPO_DOM 479..507 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT REGION 1..40 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 12..28 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 31 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 35 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 45 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT DISULFID 164 FT /note="Interchain (with C-210 in SLC3A2)" FT /evidence="ECO:0000269|PubMed:30867591" FT CROSSLNK 19 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT CROSSLNK 30 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT VARIANT 223 FT /note="D -> V (in dbSNP:rs17853937)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_070119" FT VARIANT 230 FT /note="N -> K (in dbSNP:rs1060250)" FT /evidence="ECO:0000269|PubMed:9751058" FT /id="VAR_048157" FT MUTAGEN 117 FT /note="Y->A: Strongly decreased leucine transport FT activity." FT /evidence="ECO:0000269|PubMed:30867591" FT MUTAGEN 246 FT /note="A->V: Nearly abolishes leucine transport activity." FT /evidence="ECO:0000269|PubMed:30867591" FT MUTAGEN 252 FT /note="F->A: Nearly abolishes leucine transport activity." FT /evidence="ECO:0000269|PubMed:30867591" FT MUTAGEN 257 FT /note="W->A: Nearly abolishes leucine transport activity." FT /evidence="ECO:0000269|PubMed:30867591" FT MUTAGEN 258 FT /note="N->A: Decreased leucine transport activity." FT /evidence="ECO:0000269|PubMed:30867591" FT MUTAGEN 258 FT /note="N->D: Nearly abolishes leucine transport activity." FT /evidence="ECO:0000269|PubMed:30867591" FT MUTAGEN 259 FT /note="Y->A: Strongly decreased leucine transport FT activity." FT /evidence="ECO:0000269|PubMed:30867591" FT MUTAGEN 303 FT /note="E->K: Decreased leucine transport activity." FT /evidence="ECO:0000269|PubMed:30867591" FT MUTAGEN 375 FT /note="P->L: Nearly abolishes leucine transport activity." FT /evidence="ECO:0000269|PubMed:30867591" FT MUTAGEN 483..507 FT /note="Missing: Nearly abolishes leucine transport FT activity." FT /evidence="ECO:0000269|PubMed:30867591" FT CONFLICT 15 FT /note="A -> V (in Ref. 5; BAA75746)" FT /evidence="ECO:0000305" FT CONFLICT 29..31 FT /note="AKS -> SKR (in Ref. 5; BAA75746)" FT /evidence="ECO:0000305" FT CONFLICT 35 FT /note="S -> A (in Ref. 5; BAA75746)" FT /evidence="ECO:0000305" FT CONFLICT 62 FT /note="T -> A (in Ref. 5; BAA75746)" FT /evidence="ECO:0000305" FT CONFLICT 88 FT /note="V -> M (in Ref. 5; BAA75746)" FT /evidence="ECO:0000305" FT CONFLICT 154 FT /note="T -> A (in Ref. 5; BAA75746)" FT /evidence="ECO:0000305" FT HELIX 52..63 FT /evidence="ECO:0007829|PDB:7DSK" FT STRAND 64..66 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 67..70 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 72..79 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 82..109 FT /evidence="ECO:0007829|PDB:7DSK" FT TURN 115..117 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 118..124 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 127..138 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 140..156 FT /evidence="ECO:0007829|PDB:7DSK" FT TURN 157..160 FT /evidence="ECO:0007829|PDB:7DSK" FT STRAND 161..164 FT /evidence="ECO:0007829|PDB:6JMQ" FT HELIX 168..188 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 190..219 FT /evidence="ECO:0007829|PDB:7DSK" FT STRAND 224..226 FT /evidence="ECO:0007829|PDB:6IRS" FT TURN 229..235 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 240..242 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 244..252 FT /evidence="ECO:0007829|PDB:7DSK" FT TURN 253..258 FT /evidence="ECO:0007829|PDB:7DSL" FT TURN 260..265 FT /evidence="ECO:0007829|PDB:7DSK" FT STRAND 266..269 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 270..273 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 275..297 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 302..306 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 311..319 FT /evidence="ECO:0007829|PDB:7DSK" FT STRAND 321..323 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 326..355 FT /evidence="ECO:0007829|PDB:7DSK" FT STRAND 363..366 FT /evidence="ECO:0007829|PDB:7DSK" FT TURN 368..370 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 374..386 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 387..389 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 394..396 FT /evidence="ECO:0007829|PDB:7DSN" FT HELIX 397..421 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 435..450 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 455..465 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 468..472 FT /evidence="ECO:0007829|PDB:7DSK" FT TURN 473..476 FT /evidence="ECO:0007829|PDB:7DSK" FT HELIX 483..500 FT /evidence="ECO:0007829|PDB:7DSK" SQ SEQUENCE 507 AA; 55010 MW; 767F3C60B62C0F02 CRC64; MAGAGPKRRA LAAPAAEEKE EAREKMLAAK SADGSAPAGE GEGVTLQRNI TLLNGVAIIV GTIIGSGIFV TPTGVLKEAG SPGLALVVWA ACGVFSIVGA LCYAELGTTI SKSGGDYAYM LEVYGSLPAF LKLWIELLII RPSSQYIVAL VFATYLLKPL FPTCPVPEEA AKLVACLCVL LLTAVNCYSV KAATRVQDAF AAAKLLALAL IILLGFVQIG KGDVSNLDPN FSFEGTKLDV GNIVLALYSG LFAYGGWNYL NFVTEEMINP YRNLPLAIII SLPIVTLVYV LTNLAYFTTL STEQMLSSEA VAVDFGNYHL GVMSWIIPVF VGLSCFGSVN GSLFTSSRLF FVGSREGHLP SILSMIHPQL LTPVPSLVFT CVMTLLYAFS KDIFSVINFF SFFNWLCVAL AIIGMIWLRH RKPELERPIK VNLALPVFFI LACLFLIAVS FWKTPVECGI GFTIILSGLP VYFFGVWWKN KPKWLLQGIF STTVLCQKLM QVVPQET //