LAT1_HUMAN
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 03-AUG-2022, entry version 213.
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, AND VARIANT LYS-230.
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 SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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, AND
RP TISSUE SPECIFICITY.
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, SUBCELLULAR LOCATION, SUBUNIT, AND INHIBITION.
RX PubMed=10391915; DOI=10.1074/jbc.274.28.19738;
RA Pineda M., Fernandez E., Torrents D., Estevez R., Lopez C., Camps M.,
RA Lloberas J., Zorzano A., Palacin M.;
RT "Identification of a membrane protein, LAT-2, that co-expresses with 4F2
RT heavy chain, an L-type amino acid transport activity with broad specificity
RT for small and large zwitterionic amino acids.";
RL J. Biol. Chem. 274:19738-19744(1999).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND BIOPHYSICOCHEMICAL PROPERTIES.
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 [10]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=11311135; DOI=10.1042/bj3550725;
RA Broeer A., Friedrich B., Wagner C.A., Fillon S., Ganapathy V., Lang F.,
RA Broeer S.;
RT "Association of 4F2hc with light chains LAT1, LAT2 or y+LAT2 requires
RT different domains.";
RL Biochem. J. 355:725-731(2001).
RN [11]
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 [12]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, AND
RP INHIBITION.
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 [13]
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 [14]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP INHIBITION.
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 [15]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, AND
RP INHIBITION.
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 [16]
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 [17]
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 [18]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND INHIBITION.
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 [19]
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 [20]
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 [21]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND INHIBITION.
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
RP INTERACTION WITH LAPTM4B AND SLC3A2, FUNCTION, SUBCELLULAR LOCATION, AND
RP SUBUNIT.
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 [29]
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 [30]
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 [31] {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, AND 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.
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 sodium-independent,
CC high-affinity transporter that mediates uptake of large neutral amino
CC acids such as phenylalanine, tyrosine, L-DOPA, leucine, histidine,
CC methionine and tryptophan (PubMed:9751058, PubMed:10049700,
CC PubMed:11557028, PubMed:10391915, PubMed:10574970, PubMed:11311135,
CC PubMed:11564694, PubMed:12117417, PubMed:12225859, PubMed:25998567,
CC PubMed:30867591). Functions as an amino acid exchanger
CC (PubMed:11557028, PubMed:12117417, PubMed:12225859, PubMed:30867591).
CC May play a role in the transport of L-DOPA across the blood-brain
CC barrier (By similarity). May act as the major transporter of tyrosine
CC in fibroblasts (Probable). May mediate blood-to-retina L-leucine
CC transport across the inner blood-retinal barrier (By similarity). Can
CC mediate the transport of thyroid hormones triiodothyronine (T3) and
CC thyroxine (T4) across the cell membrane (PubMed:11564694,
CC PubMed:12225859). When associated with LAPTM4B, the heterodimer formed
CC by SLC3A2 and SLC7A5 is recruited to lysosomes to promote leucine
CC uptake into these organelles, and thereby mediates mTORC1 activation
CC (PubMed:25998567). Involved in the uptake of toxic methylmercury (MeHg)
CC when administered as the L-cysteine or D,L-homocysteine complexes
CC (PubMed:12117417). Involved in the cellular activity of small molecular
CC weight nitrosothiols, via the stereoselective transport of L-
CC nitrosocysteine (L-CNSO) across the membrane (PubMed:15769744).
CC {ECO:0000250|UniProtKB:Q63016, ECO:0000250|UniProtKB:Q9Z127,
CC ECO:0000269|PubMed:10049700, ECO:0000269|PubMed:10391915,
CC ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11311135,
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:18262359,
CC ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30867591,
CC ECO:0000269|PubMed:9751058, 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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.9 uM for T4 (in the presence of choline chloride)
CC {ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:18262359};
CC KM=0.8 uM for T3 (in the presence of choline chloride)
CC {ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:18262359};
CC KM=12.5 uM for reverse triiodothyronine (rT3) (in the presence of
CC choline chloride) {ECO:0000269|PubMed:10574970,
CC ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:12117417,
CC ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:18262359};
CC KM=7.9 uM for 3,3'-diiodothyronine (in the presence of choline
CC chloride) {ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:18262359};
CC KM=46 uM for leucine (in the presence of choline chloride)
CC {ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:18262359};
CC KM=19 uM for tryptophan (in the presence of choline chloride)
CC {ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:18262359};
CC KM=32 uM for L-leucine {ECO:0000269|PubMed:10574970,
CC ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:12117417,
CC ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:18262359};
CC KM=10 mM for L-alanine {ECO:0000269|PubMed:10574970,
CC ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:12117417,
CC ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:18262359};
CC KM=2.2 mM for L-glutamine {ECO:0000269|PubMed:10574970,
CC ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:12117417,
CC ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:18262359};
CC KM=35 uM for L-histidine {ECO:0000269|PubMed:10574970,
CC ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:12117417,
CC ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:18262359};
CC KM=740 uM for L-phenylalanine {ECO:0000269|PubMed:10574970,
CC ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:12117417,
CC ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:18262359};
CC KM=98 uM for MeHg-L-cysteine {ECO:0000269|PubMed:10574970,
CC ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:12117417,
CC ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:18262359};
CC KM=99 uM for methionine {ECO:0000269|PubMed:10574970,
CC ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:12117417,
CC ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:18262359};
CC KM=55.2 uM for phenylalanine (in T24 human bladder carcinoma cells)
CC {ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:18262359};
CC KM=60.4 uM for tyrosine (in T24 human bladder carcinoma cells)
CC {ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:18262359};
CC KM=16.4 uM for tyrosine (in human fibroblasts)
CC {ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:18262359};
CC KM=138 uM for Dopa (in T24 human bladder carcinoma cells)
CC {ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:18262359};
CC KM=96.5 uM for 3-O-methyldopa (in T24 human bladder carcinoma cells)
CC {ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:18262359};
CC KM=153 uM for alpha-methyltyrosine (in T24 human bladder carcinoma
CC cells) {ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:18262359};
CC KM=216 uM for alpha-methyldopa (in T24 human bladder carcinoma cells)
CC {ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:18262359};
CC KM=191 uM for gabapentin (in T24 human bladder carcinoma cells)
CC {ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:18262359};
CC KM=7.3 uM for triiodothyronine (in T24 human bladder carcinoma cells)
CC {ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:18262359};
CC KM=162 uM for thyroxine (in T24 human bladder carcinoma cells)
CC {ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:18262359};
CC KM=75.3 uM for melphanan (in T24 human bladder carcinoma cells)
CC {ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:18262359};
CC KM=156 uM for BCH (in T24 human bladder carcinoma cells)
CC {ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:18262359};
CC -!- SUBUNIT: Disulfide-linked heterodimer with the amino acid transport
CC protein SLC3A2/4F2hc (PubMed:10049700, PubMed:10391915,
CC PubMed:10574970, PubMed:11311135, PubMed:11389679, PubMed:11557028,
CC PubMed:11564694, PubMed:12117417, PubMed:12225859, PubMed:15769744,
CC PubMed:9751058, PubMed:25998567, PubMed:30867591). Interacts with
CC LAPTM4B; this recruits the heterodimer formed by SLC3A2/4F2hc and
CC SLC7A5 to lysosomes to promote leucine uptake into these organelles and
CC is required for mTORC1 activation (PubMed:25998567).
CC {ECO:0000269|PubMed:10049700, ECO:0000269|PubMed:10391915,
CC ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11311135,
CC ECO:0000269|PubMed:11389679, 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:25998567, ECO:0000269|PubMed:30867591,
CC 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:10049700, ECO:0000269|PubMed:10391915,
CC ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11311135,
CC ECO:0000269|PubMed:11389679, 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:16496379, ECO:0000269|PubMed:25998567,
CC ECO:0000269|PubMed:9751058}; Multi-pass membrane protein
CC {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). Expressed in both luminal and
CC abluminal membranes of brain capillary endothelial cells (By
CC similarity). {ECO:0000250, 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 -!- MISCELLANEOUS: The uptake of leucine, tyrosine and tryptophan is
CC inhibited by the different iodothyronines, in particular T3. Leucine
CC transport is also inhibited by small zwitterionic amino acids (i.e.
CC glycine, alanine, serine, threonine and cysteine) and by glutamine and
CC asparagine. 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). Methionine uptake
CC was inhibited by the L-system substrates L-leucine, BCH, L-cysteine and
CC by the MeHg-L-cysteine complex and structurally related S-ethyl-L-
CC cysteine. MeHg-L-cysteine uptake is inhibited by L-methionine, L-
CC leucine, BCH and S-ethyl-L-cysteine. L-leucine uptake was inhibited by
CC L-CNSO. Tyrosine uptake in fibroblasts was inhibited by D-methionine,
CC and methyl-aminoisobutyric acid (MeAIB).
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 SMR; Q01650; -.
DR BioGRID; 113801; 155.
DR IntAct; Q01650; 51.
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; Q01650; -.
DR PeptideAtlas; Q01650; -.
DR PRIDE; Q01650; -.
DR ProteomicsDB; 57978; -.
DR TopDownProteomics; Q01650; -.
DR Antibodypedia; 17241; 403 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 CTD; 8140; -.
DR DisGeNET; 8140; -.
DR GeneCards; SLC7A5; -.
DR HGNC; HGNC:11063; SLC7A5.
DR HPA; ENSG00000103257; Tissue enhanced (bone marrow, brain).
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; RDRHLPH; -.
DR OrthoDB; 621852at2759; -.
DR PhylomeDB; Q01650; -.
DR TreeFam; TF313355; -.
DR BioCyc; MetaCyc:ENSG00000103257-MON; -.
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; 282 hits in 1096 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 190 other tissues.
DR ExpressionAtlas; Q01650; baseline and differential.
DR Genevisible; Q01650; HS.
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:0016021; C:integral component of membrane; IDA: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; HDA: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 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:0089718; P:amino acid import across plasma membrane; IDA:ARUK-UCL.
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; IEA:Ensembl.
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:0097421; P:liver regeneration; IEA:Ensembl.
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:0042476; P:odontogenesis; IEA:Ensembl.
DR GO; GO:0015823; P:phenylalanine transport; IGI:ARUK-UCL.
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:0032729; P:positive regulation of interferon-gamma production; IMP:ARUK-UCL.
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: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:ARUK-UCL.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR GO; GO:0015829; P:valine transport; IEA:Ensembl.
DR GO; GO:0042908; P:xenobiotic transport; IMP:ARUK-UCL.
DR InterPro; IPR002293; AA/rel_permease1.
DR InterPro; IPR004760; L_AA_transporter.
DR Pfam; PF13520; AA_permease_2; 1.
DR TIGRFAMs; TIGR00911; 2A0308; 1.
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 transport activity."
FT /evidence="ECO:0000269|PubMed:30867591"
FT MUTAGEN 246
FT /note="A->V: Nearly abolishes transport activity."
FT /evidence="ECO:0000269|PubMed:30867591"
FT MUTAGEN 252
FT /note="F->A: Nearly abolishes transport activity."
FT /evidence="ECO:0000269|PubMed:30867591"
FT MUTAGEN 257
FT /note="W->A: Nearly abolishes transport activity."
FT /evidence="ECO:0000269|PubMed:30867591"
FT MUTAGEN 258
FT /note="N->A: Decreased transport activity."
FT /evidence="ECO:0000269|PubMed:30867591"
FT MUTAGEN 258
FT /note="N->D: Nearly abolishes transport activity."
FT /evidence="ECO:0000269|PubMed:30867591"
FT MUTAGEN 259
FT /note="Y->A: Strongly decreased transport activity."
FT /evidence="ECO:0000269|PubMed:30867591"
FT MUTAGEN 303
FT /note="E->K: Decreased transport activity."
FT /evidence="ECO:0000269|PubMed:30867591"
FT MUTAGEN 375
FT /note="P->L: Nearly abolishes transport activity."
FT /evidence="ECO:0000269|PubMed:30867591"
FT MUTAGEN 483..507
FT /note="Missing: Nearly abolishes transport 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
