ID 4F2_HUMAN Reviewed; 630 AA. AC P08195; J3KPF3; Q13543; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 01-SEP-2009, sequence version 3. DT 27-MAR-2024, entry version 246. DE RecName: Full=Amino acid transporter heavy chain SLC3A2 {ECO:0000305}; DE AltName: Full=4F2 cell-surface antigen heavy chain {ECO:0000303|PubMed:3476959}; DE Short=4F2hc {ECO:0000303|PubMed:11557028}; DE AltName: Full=4F2 heavy chain antigen {ECO:0000303|PubMed:3036867}; DE AltName: Full=Lymphocyte activation antigen 4F2 large subunit {ECO:0000303|PubMed:3480538}; DE AltName: Full=Solute carrier family 3 member 2 {ECO:0000303|PubMed:12270127}; DE AltName: CD_antigen=CD98; GN Name=SLC3A2 {ECO:0000312|HGNC:HGNC:11026}; Synonyms=MDU1; 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] (ISOFORM 2), AND SUBCELLULAR LOCATION. RX PubMed=3476959; DOI=10.1073/pnas.84.18.6526; RA Quackenbush E., Clabby M., Gottesdiener K.M., Barbosa J., Jones N.H., RA Strominger J.L., Speck S., Leiden J.M.; RT "Molecular cloning of complementary DNAs encoding the heavy chain of the RT human 4F2 cell-surface antigen: a type II membrane glycoprotein involved in RT normal and neoplastic cell growth."; RL Proc. Natl. Acad. Sci. U.S.A. 84:6526-6530(1987). RN [2] RP ERRATUM OF PUBMED:3476959, AND SEQUENCE REVISION. RA Quackenbush E., Clabby M., Gottesdiener K.M., Barbosa J., Jones N.H., RA Strominger J.L., Speck S., Leiden J.M.; RL Proc. Natl. Acad. Sci. U.S.A. 84:8618-8618(1987). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=3036867; DOI=10.1016/s0021-9258(18)47972-0; RA Teixeira S., di Grandi S., Kuehn L.C.; RT "Primary structure of the human 4F2 antigen heavy chain predicts a RT transmembrane protein with a cytoplasmic NH2 terminus."; RL J. Biol. Chem. 262:9574-9580(1987). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, AND INDUCTION. RC TISSUE=Fibroblast; RX PubMed=3480538; DOI=10.1073/pnas.84.24.9204; RA Lumadue J.A., Glick A.B., Ruddle F.H.; RT "Cloning, sequence analysis, and expression of the large subunit of the RT human lymphocyte activation antigen 4F2."; RL Proc. Natl. Acad. Sci. U.S.A. 84:9204-9208(1987). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 2), TISSUE RP SPECIFICITY, AND INDUCTION. RX PubMed=3265470; DOI=10.1128/mcb.8.9.3809-3819.1988; RA Gottesdiener K.M., Karpinski B.A., Lindsten T., Strominger J.L., RA Jones N.H., Thompson C.B., Leiden J.M.; RT "Isolation and structural characterization of the human 4F2 heavy-chain RT gene, an inducible gene involved in T-lymphocyte activation."; RL Mol. Cell. Biol. 8:3809-3819(1988). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBUNIT, INTERACTION WITH RP SLC7A5, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RC TISSUE=Placenta; 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING RP (ISOFORM 4). RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Lung, and Placenta; 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 [10] RP PROTEIN SEQUENCE OF 1-17; 146-171; 227-245; 304-313; 440-451; 511-525 AND RP 593-630, ACETYLATION AT MET-1, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma; RA Bienvenut W.V., Lao L., Ryan K.L.; RL Submitted (OCT-2009) to UniProtKB. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 83-209 (ISOFORM 4). RC TISSUE=Lung carcinoma; RA Strausberg R.L.; RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases. RN [12] RP PROTEIN SEQUENCE OF 112-122; 148-160; 227-245; 248-255; 288-298; 304-313; RP 440-451; 511-524 AND 593-625, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=B-cell lymphoma; RA Bienvenut W.V.; RL Submitted (MAR-2005) to UniProtKB. RN [13] RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, INTERACTION WITH SLC7A7, RP INHIBITION, AND MUTAGENESIS OF CYS-210 AND CYS-431. RX PubMed=9829974; DOI=10.1074/jbc.273.49.32437; RA Torrents D., Estevez R., Pineda M., Fernandez E., Lloberas J., Shi Y.-B., RA Zorzano A., Palacin M.; RT "Identification and characterization of a membrane protein (y+L amino acid RT transporter-1) that associates with 4F2hc to encode the amino acid RT transport activity y+L. A candidate gene for lysinuric protein RT intolerance."; RL J. Biol. Chem. 273:32437-32445(1998). RN [14] RP FUNCTION, AND SUBUNIT. 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 [15] RP FUNCTION, AND SUBUNIT. RX PubMed=9878049; DOI=10.1093/emboj/18.1.49; RA Pfeiffer R., Rossier G., Spindler B., Meier C., Kuehn L.C., Verrey F.; RT "Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members RT of the glycoprotein-associated amino acid transporter family."; RL EMBO J. 18:49-57(1999). RN [16] RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION. 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 [17] RP FUNCTION, SUBUNIT, AND INTERACTION WITH SLC7A8. 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 [18] RP FUNCTION, SUBUNIT, AND INTERACTION WITH SLC7A6. RX PubMed=10903140; DOI=10.1042/bj3490787; RA Broeer A., Wagner C.A., Lang F., Broeer S.; RT "The heterodimeric amino acid transporter 4F2hc/y+LAT2 mediates arginine RT efflux in exchange with glutamine."; RL Biochem. J. 349:787-795(2000). RN [19] 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 [20] RP FUNCTION, 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 [21] RP SUBUNIT, INTERACTION WITH BETA-1 INTEGRINS, AND MUTAGENESIS OF CYS-210 AND RP CYS-431. RX PubMed=11696247; DOI=10.1186/1471-2091-2-10; RA Kolesnikova T.V., Mannion B.A., Berditchevski F., Hemler M.E.; RT "Beta1 integrins show specific association with CD98 protein in low density RT membranes."; RL BMC Biochem. 2:10-10(2001). RN [22] RP FUNCTION, AND SUBUNIT. 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 [23] RP FUNCTION, AND TOPOLOGY. RX PubMed=11121428; DOI=10.1074/jbc.m011239200; RA Fenczik C.A., Zent R., Dellos M., Calderwood D.A., Satriano J., Kelly C., RA Ginsberg M.H.; RT "Distinct domains of CD98hc regulate integrins and amino acid transport."; RL J. Biol. Chem. 276:8746-8752(2001). RN [24] RP FUNCTION, 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 [25] RP INTERACTION WITH TLCD3A/CT120. RX PubMed=12270127; DOI=10.1016/s0006-291x(02)02227-1; RA He X.H., Di Y., Li J., Xie Y., Tang Y., Zhang F., Wei L., Zhang Y., RA Qin W.X., Huo K., Li Y., Wan D.F., Gu J.R.; RT "Molecular cloning and characterization of CT120, a novel membrane- RT associated gene involved in amino acid transport and glutathione RT metabolism."; RL Biochem. Biophys. Res. Commun. 297:528-536(2002). RN [26] RP FUNCTION, AND SUBUNIT. 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 [27] RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION. 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 [28] RP MASS SPECTROMETRY. RC TISSUE=Mammary cancer; RX PubMed=11840567; RX DOI=10.1002/1615-9861(200202)2:2<212::aid-prot212>3.0.co;2-h; RA Harris R.A., Yang A., Stein R.C., Lucy K., Brusten L., Herath A., RA Parekh R., Waterfield M.D., O'Hare M.J., Neville M.A., Page M.J., RA Zvelebil M.J.; RT "Cluster analysis of an extensive human breast cancer cell line protein RT expression map database."; RL Proteomics 2:212-223(2002). RN [29] RP SUBUNIT, AND TISSUE SPECIFICITY. RX PubMed=14603368; DOI=10.1113/eph8802647; RA Arancibia-Garavilla Y., Toledo F., Casanello P., Sobrevia L.; RT "Nitric oxide synthesis requires activity of the cationic and neutral amino RT acid transport system y+L in human umbilical vein endothelium."; RL Exp. Physiol. 88:699-710(2003). RN [30] RP FUNCTION, SUBUNIT, INTERACTION WITH ICAM1, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=12716892; DOI=10.1074/jbc.m302777200; RA Liu X., Charrier L., Gewirtz A., Sitaraman S., Merlin D.; RT "CD98 and intracellular adhesion molecule I regulate the activity of amino RT acid transporter LAT-2 in polarized intestinal epithelia."; RL J. Biol. Chem. 278:23672-23677(2003). RN [31] RP GLYCOSYLATION AT ASN-365; ASN-381 AND ASN-424. RX PubMed=12754519; DOI=10.1038/nbt827; RA Zhang H., Li X.-J., Martin D.B., Aebersold R.; RT "Identification and quantification of N-linked glycoproteins using RT hydrazide chemistry, stable isotope labeling and mass spectrometry."; RL Nat. Biotechnol. 21:660-666(2003). RN [32] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=15980244; DOI=10.1167/iovs.04-1175; RA Tomi M., Mori M., Tachikawa M., Katayama K., Terasaki T., Hosoya K.; RT "L-type amino acid transporter 1-mediated L-leucine transport at the inner RT blood-retinal barrier."; RL Invest. Ophthalmol. Vis. Sci. 46:2522-2530(2005). RN [33] RP FUNCTION, AND SUBUNIT. 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 [34] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-381 AND ASN-424. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [35] RP FUNCTION. RX PubMed=15625115; DOI=10.1073/pnas.0404852102; RA Feral C.C., Nishiya N., Fenczik C.A., Stuhlmann H., Slepak M., RA Ginsberg M.H.; RT "CD98hc (SLC3A2) mediates integrin signaling."; RL Proc. Natl. Acad. Sci. U.S.A. 102:355-360(2005). RN [36] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [37] 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 [38] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Melanoma; RX PubMed=17081065; DOI=10.1021/pr060363j; RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.; RT "Proteomic and bioinformatic characterization of the biogenesis and RT function of melanosomes."; RL J. Proteome Res. 5:3135-3144(2006). RN [39] RP PHOSPHORYLATION AT SER-406; SER-408; SER-410; SER-527 AND SER-531. RX PubMed=19065266; DOI=10.1371/journal.pone.0003895; RA Nguyen H.T.T., Dalmasso G., Yan Y., Obertone T.S., Sitaraman S.V., RA Merlin D.; RT "Ecto-phosphorylation of CD98 regulates cell-cell interactions."; RL PLoS ONE 3:E3895-E3895(2008). RN [40] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2 (ISOFORM 2), CLEAVAGE OF RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS] (ISOFORM 2), AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [41] RP INDUCTION. RX PubMed=19292886; DOI=10.1111/j.1365-2362.2009.02096.x; RA Prager G.W., Poettler M., Schmidinger M., Mazal P.R., Susani M., RA Zielinski C.C., Haitel A.; RT "CD98hc (SLC3A2), a novel marker in renal cell cancer."; RL Eur. J. Clin. Invest. 39:304-310(2009). RN [42] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-365; ASN-381 AND ASN-506. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [43] RP GLYCOSYLATION AT ASN-424. RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200; RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., RA Ying W.T., He S.M., Qian X.H.; RT "A strategy for precise and large scale identification of core fucosylated RT glycoproteins."; RL Mol. Cell. Proteomics 8:913-923(2009). RN [44] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-365; ASN-381; ASN-424 AND RP ASN-506. RC TISSUE=Leukemic T-cell; RX PubMed=19349973; DOI=10.1038/nbt.1532; RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., RA Schiess R., Aebersold R., Watts J.D.; RT "Mass-spectrometric identification and relative quantification of N-linked RT cell surface glycoproteins."; RL Nat. Biotechnol. 27:378-386(2009). RN [45] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [46] 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 [47] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2 (ISOFORM 2), PHOSPHORYLATION RP [LARGE SCALE ANALYSIS] AT SER-2 (ISOFORM 2), CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS] (ISOFORM 2), AND IDENTIFICATION BY MASS RP 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 [48] RP INDUCTION. RX PubMed=23116296; DOI=10.1021/pr300555y; RA Yang Y., Toy W., Choong L.Y., Hou P., Ashktorab H., Smoot D.T., Yeoh K.G., RA Lim Y.P.; RT "Discovery of SLC3A2 cell membrane protein as a potential gastric cancer RT biomarker: implications in molecular imaging."; RL J. Proteome Res. 11:5736-5747(2012). RN [49] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2 (ISOFORM 2), CLEAVAGE OF RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS] (ISOFORM 2), AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [50] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [51] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-103; SER-134 AND SER-165, 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 [52] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [53] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-166, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25114211; DOI=10.1073/pnas.1413825111; RA Impens F., Radoshevich L., Cossart P., Ribet D.; RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by RT external stimuli."; RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014). RN [54] RP INTERACTION WITH LAPTM4B, FUNCTION, SUBCELLULAR LOCATION, AND 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 [55] 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 [56] RP INDUCTION. RX PubMed=28350098; DOI=10.3892/or.2017.5530; RA Zhu B., Cheng D., Hou L., Zhou S., Ying T., Yang Q.; RT "SLC3A2 is upregulated in human osteosarcoma and promotes tumor growth RT through the PI3K/Akt signaling pathway."; RL Oncol. Rep. 37:2575-2582(2017). RN [57] RP FUNCTION, FUNCTION (MICROBIAL INFECTION), INDUCTION BY HCV (MICROBIAL RP INFECTION), INDUCTION BY HYDROGEN PEROXIDE, AND INTERACTION WITH HEPATITIS RP VIRUS C/HCV PROTEIN E2 (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 [58] RP FUNCTION. RX PubMed=33066406; DOI=10.3390/ijms21207573; RA Kantipudi S., Jeckelmann J.M., Ucurum Z., Bosshart P.D., Fotiadis D.; RT "The Heavy Chain 4F2hc Modulates the Substrate Affinity and Specificity of RT the Light Chains LAT1 and LAT2."; RL Int. J. Mol. Sci. 21:0-0(2020). RN [59] RP FUNCTION (MICROBIAL INFECTION), AND TISSUE SPECIFICITY. RX PubMed=34294905; DOI=10.1038/s41564-021-00939-3; RA Malleret B., El Sahili A., Tay M.Z., Carissimo G., Ong A.S.M., Novera W., RA Lin J., Suwanarusk R., Kosaisavee V., Chu T.T.T., Sinha A., Howland S.W., RA Fan Y., Gruszczyk J., Tham W.H., Colin Y., Maurer-Stroh S., Snounou G., RA Ng L.F.P., Chan J.K.Y., Chacko A.M., Lescar J., Chandramohanadas R., RA Nosten F., Russell B., Renia L.; RT "Plasmodium vivax binds host CD98hc (SLC3A2) to enter immature red blood RT cells."; RL Nat. Microbiol. 6:991-999(2021). RN [60] RP SUBCELLULAR LOCATION, GLYCOSYLATION, AND MUTAGENESIS OF ASN-365; ASN-381; RP ASN-424 AND ASN-506. RX PubMed=36028562; DOI=10.1038/s41598-022-18779-4; RA Console L., Scalise M., Salerno S., Scanga R., Giudice D., De Bartolo L., RA Tonazzi A., Indiveri C.; RT "N-glycosylation is crucial for trafficking and stability of SLC3A2 RT (CD98)."; RL Sci. Rep. 12:14570-14570(2022). RN [61] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 212-630, SUBUNIT, MUTAGENESIS OF RP CYS-210, SUBCELLULAR LOCATION, AND DISULFIDE BOND. RX PubMed=17724034; DOI=10.1074/jbc.m704524200; RA Fort J., de la Ballina L.R., Burghardt H.E., Ferrer-Costa C., Turnay J., RA Ferrer-Orta C., Uson I., Zorzano A., Fernandez-Recio J., Orozco M., RA Lizarbe M.A., Fita I., Palacin M.; RT "The structure of human 4F2hc ectodomain provides a model for RT homodimerization and electrostatic interaction with plasma membrane."; RL J. Biol. Chem. 282:31444-31452(2007). RN [62] {ECO:0007744|PDB:6IRS, ECO:0007744|PDB:6IRT} RP STRUCTURE BY ELECTRON MICROSCOPY (3.30 ANGSTROMS) IN COMPLEX WITH SLC7A5, RP FUNCTION, SUBUNIT, TOPOLOGY, GLYCOSYLATION AT ASN-365; ASN-381; ASN-424 AND RP ASN-506, DISULFIDE BOND, AND MUTAGENESIS OF ARG-182; 234-GLN--ALA-630 AND RP LYS-532. 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). RN [63] {ECO:0007744|PDB:7CMH, ECO:0007744|PDB:7CMI} RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) OF IN COMPLEX WITH RP SLC7A8; TRYPTOPHAN AND LEUCINE, GLYCOSYLATION AT ASN-365; ASN-381; ASN-424 RP AND ASN-506, FUNCTION, AND DISULFIDE BOND. RX PubMed=33298890; DOI=10.1038/s41421-020-00207-4; RA Yan R., Zhou J., Li Y., Lei J., Zhou Q.; RT "Structural insight into the substrate recognition and transport mechanism RT of the human LAT2-4F2hc complex."; RL Cell Discov. 6:82-82(2020). RN [64] {ECO:0007744|PDB:7DSK, ECO:0007744|PDB:7DSL, ECO:0007744|PDB:7DSN, ECO:0007744|PDB:7DSQ} RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) OF 2-507 IN COMPLEX WITH RP SLC7A8, GLYCOSYLATION AT ASN-365; ASN-381; ASN-424 AND ASN-506, AND RP DISULFIDE BOND. RX PubMed=33758168; DOI=10.1038/s41421-021-00247-4; RA Yan R., Li Y., Muller J., Zhang Y., Singer S., Xia L., Zhong X., RA Gertsch J., Altmann K.H., Zhou Q.; RT "Mechanism of substrate transport and inhibition of the human LAT1-4F2hc RT amino acid transporter."; RL Cell Discov. 7:16-16(2021). RN [65] {ECO:0007744|PDB:7P9U, ECO:0007744|PDB:7P9V} RP STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF 2-630 IN COMPLEX WITH RP SLC7A11, AND GLYCOSYLATION AT ASN-365; ASN-381; ASN-424 AND ASN-506. RX PubMed=34880232; DOI=10.1038/s41467-021-27414-1; RA Parker J.L., Deme J.C., Kolokouris D., Kuteyi G., Biggin P.C., Lea S.M., RA Newstead S.; RT "Molecular basis for redox control by the human cystine/glutamate RT antiporter system xc."; RL Nat. Commun. 12:7147-7147(2021). RN [66] {ECO:0007744|PDB:7EPZ} RP STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF 2-630 IN COMPLEX WITH RP SLC7A11, DISULFIDE BOND, AND GLYCOSYLATION AT ASN-365; ASN-381; ASN-424 AND RP ASN-506. RX PubMed=35352032; DOI=10.1038/s41422-022-00642-w; RA Yan R., Xie E., Li Y., Li J., Zhang Y., Chi X., Hu X., Xu L., Hou T., RA Stockwell B.R., Min J., Zhou Q., Wang F.; RT "The structure of erastin-bound xCT-4F2hc complexreveals molecular RT mechanisms underlying erastin-induced ferroptosis."; RL Cell Res. 32:687-690(2022). CC -!- FUNCTION: Acts as a chaperone that facilitates biogenesis and CC trafficking of functional transporters heterodimers to the plasma CC membrane. Forms heterodimer with SLC7 family transporters (SLC7A5, CC SLC7A6, SLC7A7, SLC7A8, SLC7A10 and SLC7A11), a group of amino-acid CC antiporters (PubMed:11557028, PubMed:9829974, PubMed:9751058, CC PubMed:9878049, PubMed:10574970, PubMed:10903140, PubMed:30867591, CC PubMed:33298890, PubMed:33758168, PubMed:34880232). Heterodimers CC function as amino acids exchangers, the specificity of the substrate CC depending on the SLC7A subunit. Heterodimers SLC3A2/SLC7A6 or CC SLC3A2/SLC7A7 mediate the uptake of dibasic amino acids CC (PubMed:9829974, PubMed:10903140). Heterodimer SLC3A2/SLC7A11 functions CC as an antiporter by mediating the exchange of extracellular anionic L- CC cystine and intracellular L-glutamate across the cellular plasma CC membrane (PubMed:34880232). SLC3A2/SLC7A10 translocates small neutral CC L- and D-amino acids across the plasma membrane (By similarity). CC SLC3A2/SLC75 or SLC3A2/SLC7A8 translocates neutral amino acids with CC broad specificity, thyroid hormones and L-DOPA (PubMed:11557028, CC PubMed:10574970, PubMed:11389679, PubMed:11564694, PubMed:11742812, CC PubMed:12117417, PubMed:12225859, PubMed:15980244, PubMed:12716892, CC PubMed:33298890, PubMed:33758168, PubMed:30867591). SLC3A2 is essential CC for plasma membrane localization, stability, and the transport activity CC of SLC7A5 and SLC7A8 (PubMed:10391915, PubMed:10574970, CC PubMed:11311135, PubMed:15769744, PubMed:33066406). When associated CC with LAPTM4B, the heterodimer SLC7A5 is recruited to lysosomes to CC promote leucine uptake into these organelles, and thereby mediates CC mTORC1 activation (PubMed:25998567). Modulates integrin-related CC signaling and is essential for integrin-dependent cell spreading, CC migration and tumor progression (PubMed:15625115, PubMed:11121428). CC {ECO:0000250|UniProtKB:P63115, ECO:0000269|PubMed:10391915, CC ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:10903140, CC ECO:0000269|PubMed:11121428, ECO:0000269|PubMed:11311135, CC ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, CC ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:11742812, CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, CC ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:15625115, CC ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15980244, CC ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30867591, CC ECO:0000269|PubMed:33066406, ECO:0000269|PubMed:33298890, CC ECO:0000269|PubMed:33758168, ECO:0000269|PubMed:34880232, CC ECO:0000269|PubMed:9751058, ECO:0000269|PubMed:9829974, CC ECO:0000269|PubMed:9878049}. 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 -!- FUNCTION: (Microbial infection) Acts as a receptor for malaria parasite CC Plasmodium vivax (Thai isolate) in immature red blood cells. CC {ECO:0000269|PubMed:34294905}. CC -!- SUBUNIT: Disulfide-linked heterodimer with a non-glycosylated catalytic CC light subunit (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 or SLC7A11) CC (PubMed:11557028, PubMed:9829974, PubMed:9751058, PubMed:10574970, CC PubMed:10903140, PubMed:11311135, PubMed:30867591, PubMed:9751058, CC PubMed:12225859, PubMed:12117417, PubMed:15769744, PubMed:33298890, CC PubMed:33758168, PubMed:34880232, PubMed:35352032). Interacts with CC TLCD3A/CT120 (PubMed:12270127). Interacts with ICAM1 (PubMed:12716892). CC Constitutively and specifically associates with beta-1 integrins CC (alpha-2/beta-1, alpha-3/beta-1, alpha-5/beta-1 and alpha-6/beta-1), CC but minimally with alpha-4/beta-1 (PubMed:11696247). Interacts with CC LAPTM4B; recruits SLC3A2 and SLC7A5/LAT1 to lysosomes to promote CC leucine uptake into these organelles and is required for mTORC1 CC activation (PubMed:25998567). {ECO:0000269|PubMed:10574970, CC ECO:0000269|PubMed:10903140, ECO:0000269|PubMed:11311135, CC ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, CC ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:11696247, CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, CC ECO:0000269|PubMed:12270127, ECO:0000269|PubMed:12716892, CC ECO:0000269|PubMed:14603368, ECO:0000269|PubMed:15769744, CC ECO:0000269|PubMed:17724034, ECO:0000269|PubMed:25998567, CC ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:33298890, CC ECO:0000269|PubMed:33758168, ECO:0000269|PubMed:34880232, CC ECO:0000269|PubMed:35352032, ECO:0000269|PubMed:9751058, CC ECO:0000269|PubMed:9829974, ECO:0000269|PubMed:9878049}. CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis C virus/HCV CC envelope glycoprotein E2; the interaction may facilitate viral entry CC into host cell. {ECO:0000269|PubMed:30341327}. CC -!- INTERACTION: CC P08195; O15354: GPR37; NbExp=3; IntAct=EBI-702356, EBI-15639515; CC P08195; Q01650: SLC7A5; NbExp=2; IntAct=EBI-702356, EBI-6138761; CC P08195; O52302: sepZ; Xeno; NbExp=5; IntAct=EBI-702356, EBI-14022357; CC P08195-1; Q01650: SLC7A5; NbExp=3; IntAct=EBI-11614088, EBI-6138761; CC P08195-4; Q9NX09: DDIT4; NbExp=3; IntAct=EBI-12832276, EBI-715104; CC P08195-4; Q15125: EBP; NbExp=3; IntAct=EBI-12832276, EBI-3915253; CC P08195-4; P21333-2: FLNA; NbExp=3; IntAct=EBI-12832276, EBI-9641086; CC P08195-4; P04792: HSPB1; NbExp=3; IntAct=EBI-12832276, EBI-352682; CC P08195-4; O60333-2: KIF1B; NbExp=3; IntAct=EBI-12832276, EBI-10975473; CC P08195-4; Q5T3J3: LRIF1; NbExp=3; IntAct=EBI-12832276, EBI-473196; CC P08195-4; P31153: MAT2A; NbExp=3; IntAct=EBI-12832276, EBI-1050743; CC P08195-4; Q9UPY5: SLC7A11; NbExp=3; IntAct=EBI-12832276, EBI-3843348; CC P08195-4; Q9UHI5: SLC7A8; NbExp=3; IntAct=EBI-12832276, EBI-13292283; CC P08195-4; O76024: WFS1; NbExp=3; IntAct=EBI-12832276, EBI-720609; CC P08195-4; Q96BH6; NbExp=3; IntAct=EBI-12832276, EBI-25872486; CC -!- SUBCELLULAR LOCATION: Apical cell membrane CC {ECO:0000269|PubMed:11742812}. Cell membrane CC {ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679, CC ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, CC ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:15769744, CC ECO:0000269|PubMed:16496379, ECO:0000269|PubMed:25998567, CC ECO:0000269|PubMed:3476959, ECO:0000269|PubMed:3480538, CC ECO:0000269|PubMed:36028562, ECO:0000269|PubMed:9829974}; Single-pass CC type II membrane protein {ECO:0000269|PubMed:30867591}. Cell junction CC {ECO:0000250|UniProtKB:P10852}. Lysosome membrane CC {ECO:0000269|PubMed:25998567}. Melanosome CC {ECO:0000269|PubMed:17081065}. Basolateral cell membrane CC {ECO:0000250|UniProtKB:P10852}. Note=Localized at the plasma membrane CC when associated with SLC7A5/LAT1 or SLC7A8/LAT2 (PubMed:9751058, CC PubMed:11311135). Localized to the apical membrane of placental CC syncytiotrophoblastic cells (PubMed:11742812). Recruited to lysosomes CC by LAPTM4B (PubMed:25998567). Identified by mass spectrometry in CC melanosome fractions from stage I to stage IV (PubMed:17081065). CC Located selectively at cell-cell adhesion sites (By similarity). CC Colocalized with SLC7A8/LAT2 at the basolateral membrane of kidney CC proximal tubules and small intestine epithelia. Expressed in both CC luminal and abluminal membranes of brain capillary endothelial cells CC (By similarity). {ECO:0000250|UniProtKB:P10852, CC ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11742812, CC ECO:0000269|PubMed:17081065, ECO:0000269|PubMed:25998567, CC ECO:0000269|PubMed:9751058}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=P08195-1; Sequence=Displayed; CC Name=2; CC IsoId=P08195-2; Sequence=VSP_037907; CC Name=3; CC IsoId=P08195-3; Sequence=VSP_037908; CC Name=4; CC IsoId=P08195-4; Sequence=VSP_037909; CC Name=5; CC IsoId=P08195-5; Sequence=VSP_061769; CC -!- TISSUE SPECIFICITY: Expressed ubiquitously in all tissues tested with CC highest levels detected in kidney, placenta and testis and weakest CC level in thymus. During gestation, expression in the placenta was CC significantly stronger at full-term than at the mid-trimester stage. CC Expressed in HUVECS and at low levels in resting peripheral blood T- CC lymphocytes and quiescent fibroblasts. Also expressed in fetal liver CC and in the astrocytic process of primary astrocytic gliomas. Expressed CC in retinal endothelial cells and in the intestinal epithelial cell line CC C2BBe1. {ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, CC ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:12716892, CC ECO:0000269|PubMed:14603368, ECO:0000269|PubMed:15980244, CC ECO:0000269|PubMed:16496379, ECO:0000269|PubMed:3265470, CC ECO:0000269|PubMed:3480538}. CC -!- INDUCTION: Expression is induced in resting peripheral blood T- CC lymphocytes following PHA stimulation. Expression increases at the time CC of maximal DNA synthesis, in fibroblasts stimulated to divide. CC Expression and the uptake of leucine is stimulated in mononuclear, CC cytotrophoblast-like choriocarcinoma cells by combined treatment with CC PMA and calcium ionophore. Up-regulated in response to hydrogen CC peroxide (PubMed:30341327). Highly expressed in various cancer types CC (PubMed:23116296, PubMed:28350098, PubMed:19292886). CC {ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:19292886, CC ECO:0000269|PubMed:23116296, ECO:0000269|PubMed:28350098, CC ECO:0000269|PubMed:30341327, ECO:0000269|PubMed:3265470, CC ECO:0000269|PubMed:3480538}. CC -!- INDUCTION: (Microbial infection) Up-regulated upon hepatitis C CC virus/HCV infection via NS3-A4 viral protein complex; the up-regulation CC is mediated by oxidative stress (PubMed:30341327). Up-regulation of the CC complex formed by SLC3A2 and SLC7A5/LAT1 upon hepatitis C virus/HCV CC infection (PubMed:30341327). {ECO:0000269|PubMed:30341327}. CC -!- PTM: N-glycosylated; N-glycosylation is crucial for trafficking and CC stability of SLC3A2 to the plasma membrane. CC {ECO:0000269|PubMed:36028562}. CC -!- PTM: Phosphorylation on Ser-406; Ser-408 or Ser-410 and on Ser-527 or CC Ser-531 by ecto-protein kinases favors heterotypic cell-cell CC interactions. {ECO:0000269|PubMed:19065266}. CC -!- MASS SPECTROMETRY: Mass=57944.93; Method=MALDI; CC Evidence={ECO:0000269|PubMed:11840567}; CC -!- SIMILARITY: Belongs to the SLC3A transporter family. {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; J02939; AAA52497.1; -; mRNA. DR EMBL; J02769; AAA51540.1; -; mRNA. DR EMBL; J03569; AAA35536.1; -; mRNA. DR EMBL; M21904; AAA35489.1; -; Genomic_DNA. DR EMBL; M21898; AAA35489.1; JOINED; Genomic_DNA. DR EMBL; M21899; AAA35489.1; JOINED; Genomic_DNA. DR EMBL; M21900; AAA35489.1; JOINED; Genomic_DNA. DR EMBL; M21901; AAA35489.1; JOINED; Genomic_DNA. DR EMBL; M21902; AAA35489.1; JOINED; Genomic_DNA. DR EMBL; M21903; AAA35489.1; JOINED; Genomic_DNA. DR EMBL; AB018010; BAA84649.1; -; mRNA. DR EMBL; AP001160; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471076; EAW74118.1; -; Genomic_DNA. DR EMBL; BC001061; AAH01061.2; -; mRNA. DR EMBL; BC003000; AAH03000.2; -; mRNA. DR EMBL; BE794697; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS31588.1; -. [P08195-5] DR CCDS; CCDS31589.1; -. [P08195-3] DR CCDS; CCDS31590.1; -. [P08195-2] DR CCDS; CCDS8039.2; -. [P08195-1] DR PIR; A28455; SAHU4F. DR RefSeq; NP_001012680.1; NM_001012662.2. [P08195-5] DR RefSeq; NP_001012682.1; NM_001012664.2. [P08195-3] DR RefSeq; NP_001013269.1; NM_001013251.2. [P08195-2] DR RefSeq; NP_002385.3; NM_002394.5. [P08195-1] DR PDB; 2DH2; X-ray; 2.10 A; A=212-630. DR PDB; 2DH3; X-ray; 2.80 A; A/B=212-630. DR PDB; 6IRS; EM; 3.30 A; A=1-630. DR PDB; 6IRT; EM; 3.50 A; A=1-630. DR PDB; 6JMQ; EM; 3.31 A; B=2-630. DR PDB; 6JMR; EM; 4.10 A; B=2-630. DR PDB; 6S8V; X-ray; 1.80 A; B/D=212-630. DR PDB; 7B00; EM; 3.98 A; B=102-630. DR PDB; 7CCS; EM; 6.20 A; A=2-630. DR PDB; 7CMH; EM; 3.40 A; A=2-630. DR PDB; 7CMI; EM; 2.90 A; A=2-630. DR PDB; 7DF1; X-ray; 2.81 A; A/B/C/D=212-630. DR PDB; 7DSK; EM; 2.90 A; A=2-630. DR PDB; 7DSL; EM; 2.90 A; A=2-630. DR PDB; 7DSN; EM; 3.10 A; A=2-630. DR PDB; 7DSQ; EM; 3.40 A; A=2-630. DR PDB; 7EPZ; EM; 3.40 A; A=2-630. DR PDB; 7P9U; EM; 3.70 A; A=2-630. DR PDB; 7P9V; EM; 3.40 A; A=2-630. DR PDB; 8A6L; EM; 3.18 A; A=98-630. DR PDB; 8G0M; X-ray; 2.25 A; A=212-630. DR PDBsum; 2DH2; -. DR PDBsum; 2DH3; -. DR PDBsum; 6IRS; -. DR PDBsum; 6IRT; -. DR PDBsum; 6JMQ; -. DR PDBsum; 6JMR; -. DR PDBsum; 6S8V; -. DR PDBsum; 7B00; -. DR PDBsum; 7CCS; -. DR PDBsum; 7CMH; -. DR PDBsum; 7CMI; -. DR PDBsum; 7DF1; -. DR PDBsum; 7DSK; -. DR PDBsum; 7DSL; -. DR PDBsum; 7DSN; -. DR PDBsum; 7DSQ; -. DR PDBsum; 7EPZ; -. DR PDBsum; 7P9U; -. DR PDBsum; 7P9V; -. DR PDBsum; 8A6L; -. DR PDBsum; 8G0M; -. DR AlphaFoldDB; P08195; -. DR EMDB; EMD-11726; -. DR EMDB; EMD-11952; -. DR EMDB; EMD-13266; -. DR EMDB; EMD-13267; -. DR EMDB; EMD-15210; -. DR EMDB; EMD-30341; -. DR EMDB; EMD-30406; -. DR EMDB; EMD-30407; -. DR EMDB; EMD-30835; -. DR EMDB; EMD-30837; -. DR EMDB; EMD-30839; -. DR EMDB; EMD-30841; -. DR EMDB; EMD-31251; -. DR EMDB; EMD-4642; -. DR EMDB; EMD-9721; -. DR EMDB; EMD-9722; -. DR EMDB; EMD-9849; -. DR EMDB; EMD-9850; -. DR SMR; P08195; -. DR BioGRID; 112411; 427. DR ComplexPortal; CPX-8185; LAT1-4F2 heteromeric amino acid transporter complex. DR ComplexPortal; CPX-8186; LAT2-4F2 heteromeric amino acid transporter complex. DR ComplexPortal; CPX-8187; Y+LAT1-4F2 heteromeric amino acid transporter complex. DR ComplexPortal; CPX-8188; Y+LAT2-4F2 heteromeric amino acid transporter complex. DR ComplexPortal; CPX-8189; ASC1-4F2 heteromeric amino acid transporter complex. DR ComplexPortal; CPX-8190; XCT-4F2 heteromeric amino acid transporter complex. DR CORUM; P08195; -. DR IntAct; P08195; 121. DR MINT; P08195; -. DR STRING; 9606.ENSP00000367123; -. DR GuidetoPHARMACOLOGY; 890; -. DR CAZy; GH13; Glycoside Hydrolase Family 13. DR TCDB; 2.A.3.8.18; the amino acid-polyamine-organocation (apc) family. DR TCDB; 8.A.9.2.2; the rbat transport accessory protein (rbat) family. DR GlyConnect; 984; 54 N-Linked glycans (3 sites). DR GlyCosmos; P08195; 4 sites, 51 glycans. DR GlyGen; P08195; 6 sites, 51 N-linked glycans (3 sites), 1 O-linked glycan (1 site). DR iPTMnet; P08195; -. DR MetOSite; P08195; -. DR PhosphoSitePlus; P08195; -. DR SwissPalm; P08195; -. DR BioMuta; SLC3A2; -. DR DMDM; 257051063; -. DR EPD; P08195; -. DR jPOST; P08195; -. DR MassIVE; P08195; -. DR MaxQB; P08195; -. DR PaxDb; 9606-ENSP00000367123; -. DR PeptideAtlas; P08195; -. DR PRIDE; J3KPF3; -. DR ProteomicsDB; 52082; -. [P08195-1] DR ProteomicsDB; 52083; -. [P08195-2] DR ProteomicsDB; 52084; -. [P08195-3] DR ProteomicsDB; 52085; -. [P08195-4] DR Pumba; P08195; -. DR ABCD; P08195; 55 sequenced antibodies. DR Antibodypedia; 15042; 1216 antibodies from 46 providers. DR DNASU; 6520; -. DR Ensembl; ENST00000338663.12; ENSP00000340815.7; ENSG00000168003.19. [P08195-2] DR Ensembl; ENST00000377889.6; ENSP00000367121.2; ENSG00000168003.19. [P08195-3] DR Ensembl; ENST00000377890.6; ENSP00000367122.2; ENSG00000168003.19. [P08195-1] DR Ensembl; ENST00000377891.6; ENSP00000367123.2; ENSG00000168003.19. [P08195-5] DR Ensembl; ENST00000538084.2; ENSP00000440001.2; ENSG00000168003.19. [P08195-4] DR Ensembl; ENST00000544377.2; ENSP00000442135.2; ENSG00000168003.19. [P08195-2] DR Ensembl; ENST00000680631.1; ENSP00000506006.1; ENSG00000168003.19. [P08195-2] DR Ensembl; ENST00000681657.1; ENSP00000505110.1; ENSG00000168003.19. [P08195-2] DR GeneID; 6520; -. DR KEGG; hsa:6520; -. DR MANE-Select; ENST00000338663.12; ENSP00000340815.7; NM_001013251.3; NP_001013269.1. [P08195-2] DR UCSC; uc001nwd.4; human. [P08195-1] DR AGR; HGNC:11026; -. DR CTD; 6520; -. DR DisGeNET; 6520; -. DR GeneCards; SLC3A2; -. DR HGNC; HGNC:11026; SLC3A2. DR HPA; ENSG00000168003; Low tissue specificity. DR MIM; 158070; gene. DR neXtProt; NX_P08195; -. DR OpenTargets; ENSG00000168003; -. DR PharmGKB; PA35894; -. DR VEuPathDB; HostDB:ENSG00000168003; -. DR eggNOG; KOG0471; Eukaryota. DR GeneTree; ENSGT00940000156646; -. DR HOGENOM; CLU_006462_9_0_1; -. DR InParanoid; P08195; -. DR OrthoDB; 4266085at2759; -. DR PhylomeDB; P08195; -. DR TreeFam; TF314498; -. DR BioCyc; MetaCyc:ENSG00000168003-MONOMER; -. DR PathwayCommons; P08195; -. DR Reactome; R-HSA-210991; Basigin interactions. DR Reactome; R-HSA-352230; Amino acid transport across the plasma membrane. DR Reactome; R-HSA-5660862; Defective SLC7A7 causes lysinuric protein intolerance (LPI). DR Reactome; R-HSA-71240; Tryptophan catabolism. DR SABIO-RK; P08195; -. DR SignaLink; P08195; -. DR SIGNOR; P08195; -. DR BioGRID-ORCS; 6520; 194 hits in 1175 CRISPR screens. DR ChiTaRS; SLC3A2; human. DR EvolutionaryTrace; P08195; -. DR GeneWiki; SLC3A2; -. DR GenomeRNAi; 6520; -. DR Pharos; P08195; Tbio. DR PRO; PR:P08195; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P08195; Protein. DR Bgee; ENSG00000168003; Expressed in islet of Langerhans and 206 other cell types or tissues. DR ExpressionAtlas; P08195; baseline and differential. DR GO; GO:1990184; C:amino acid transport complex; IDA:UniProtKB. DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell. DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL. DR GO; GO:0044225; C:apical pole of neuron; IEA:Ensembl. DR GO; GO:0009925; C:basal plasma membrane; ISS:ARUK-UCL. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:ARUK-UCL. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell. DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0045202; C:synapse; IEA:Ensembl. DR GO; GO:0015173; F:aromatic amino acid transmembrane transporter activity; IGI:ARUK-UCL. DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL. DR GO; GO:0005432; F:calcium:sodium antiporter activity; TAS:UniProtKB. DR GO; GO:0003725; F:double-stranded RNA binding; IDA:MGI. DR GO; GO:0140272; F:exogenous protein binding; IDA:UniProtKB. DR GO; GO:0015180; F:L-alanine transmembrane transporter activity; IGI:ARUK-UCL. DR GO; GO:0015190; F:L-leucine transmembrane transporter activity; IGI:ARUK-UCL. DR GO; GO:0005294; F:neutral L-amino acid secondary active transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015175; F:neutral L-amino acid transmembrane transporter activity; IGI:ARUK-UCL. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW. DR GO; GO:0006865; P:amino acid transport; TAS:UniProtKB. DR GO; GO:0006816; P:calcium ion transport; NAS:UniProtKB. DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro. DR GO; GO:0015818; P:isoleucine transport; IDA:UniProtKB. DR GO; GO:1904273; P:L-alanine import across plasma membrane; IGI:ARUK-UCL. DR GO; GO:1902024; P:L-histidine transport; IDA:UniProtKB. DR GO; GO:1903801; P:L-leucine import across plasma membrane; IGI:ARUK-UCL. DR GO; GO:0098713; P:leucine import across plasma membrane; IGI:ARUK-UCL. DR GO; GO:0015820; P:leucine transport; IDA:UniProtKB. DR GO; GO:0015821; P:methionine transport; IDA:UniProtKB. DR GO; GO:0015823; P:phenylalanine transport; IDA:UniProtKB. DR GO; GO:0015824; P:proline transport; IDA:UniProtKB. DR GO; GO:0043330; P:response to exogenous dsRNA; IMP:MGI. DR GO; GO:0070327; P:thyroid hormone transport; IDA:UniProtKB. 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:0046718; P:viral entry into host cell; IMP:UniProtKB. DR CDD; cd11345; AmyAc_SLC3A2; 1. DR Gene3D; 3.20.20.80; Glycosidases; 1. DR Gene3D; 2.60.40.1180; Golgi alpha-mannosidase II; 1. DR InterPro; IPR006047; Glyco_hydro_13_cat_dom. DR InterPro; IPR013780; Glyco_hydro_b. DR InterPro; IPR017853; Glycoside_hydrolase_SF. DR InterPro; IPR042280; SLC3A2. DR InterPro; IPR031984; SLC3A2_N. DR PANTHER; PTHR46673; 4F2 CELL-SURFACE ANTIGEN HEAVY CHAIN; 1. DR PANTHER; PTHR46673:SF1; 4F2 CELL-SURFACE ANTIGEN HEAVY CHAIN; 1. DR Pfam; PF00128; Alpha-amylase; 1. DR Pfam; PF16028; SLC3A2_N; 1. DR PRINTS; PR02045; F138DOMAIN. DR SMART; SM00642; Aamy; 1. DR SUPFAM; SSF51445; (Trans)glycosidases; 1. DR SUPFAM; SSF51011; Glycosyl hydrolase domain; 1. DR Genevisible; P08195; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Amino-acid transport; KW Cell junction; Cell membrane; Direct protein sequencing; Disulfide bond; KW Glycoprotein; Host cell receptor for virus entry; Isopeptide bond; KW Lysosome; Membrane; Phosphoprotein; Receptor; Reference proteome; KW Signal-anchor; Transmembrane; Transmembrane helix; Transport; KW Ubl conjugation. FT CHAIN 1..630 FT /note="Amino acid transporter heavy chain SLC3A2" FT /id="PRO_0000064383" FT TOPO_DOM 102..184 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:11121428, FT ECO:0000269|PubMed:30867591" FT TRANSMEM 185..205 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000269|PubMed:30867591" FT TOPO_DOM 206..630 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:11121428, FT ECO:0000269|PubMed:30867591" FT REGION 15..39 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000269|Ref.10, ECO:0007744|PubMed:22814378" FT MOD_RES 103 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 106 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q794F9" FT MOD_RES 134 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 165 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 406 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:19065266" FT MOD_RES 408 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:19065266" FT MOD_RES 410 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:19065266" FT MOD_RES 527 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:19065266" FT MOD_RES 531 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:19065266" FT CARBOHYD 365 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19349973, FT ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:33298890, FT ECO:0000269|PubMed:33758168, ECO:0000269|PubMed:34880232, FT ECO:0000269|PubMed:35352032, ECO:0007744|PDB:6IRS, FT ECO:0007744|PDB:7CMI, ECO:0007744|PDB:7DSK, FT ECO:0007744|PDB:7EPZ, ECO:0007744|PDB:7P9V" FT CARBOHYD 381 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:19349973, ECO:0000269|PubMed:30867591, FT ECO:0000269|PubMed:33298890, ECO:0000269|PubMed:33758168, FT ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:35352032, FT ECO:0007744|PDB:6IRS, ECO:0007744|PDB:7CMI, FT ECO:0007744|PDB:7DSK, ECO:0007744|PDB:7EPZ, FT ECO:0007744|PDB:7P9V" FT CARBOHYD 424 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:12754519, FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19139490, FT ECO:0000269|PubMed:19349973, ECO:0000269|PubMed:30867591, FT ECO:0000269|PubMed:33298890, ECO:0000269|PubMed:33758168, FT ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:35352032, FT ECO:0007744|PDB:6IRS, ECO:0007744|PDB:7CMI, FT ECO:0007744|PDB:7DSK, ECO:0007744|PDB:7EPZ, FT ECO:0007744|PDB:7P9V" FT CARBOHYD 506 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:19349973, ECO:0000269|PubMed:30867591, FT ECO:0000269|PubMed:33298890, ECO:0000269|PubMed:33758168, FT ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:35352032, FT ECO:0007744|PDB:6IRS, ECO:0007744|PDB:7CMH, FT ECO:0007744|PDB:7DSK, ECO:0007744|PDB:7EPZ, FT ECO:0007744|PDB:7P9V" FT DISULFID 210 FT /note="Interchain (with C-164 in SLC7A5; C-158 in SLC7A11 FT and C-154 in SLC7A8)" FT /evidence="ECO:0000269|PubMed:30867591, FT ECO:0000269|PubMed:33298890, ECO:0000269|PubMed:35352032, FT ECO:0000305|PubMed:17724034, ECO:0007744|PDB:7EPZ" FT CROSSLNK 147 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT CROSSLNK 166 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25114211" FT VAR_SEQ 1..101 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11557028, FT ECO:0000303|PubMed:3036867, ECO:0000303|PubMed:3476959, FT ECO:0000303|PubMed:3480538" FT /id="VSP_037907" FT VAR_SEQ 38..99 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_037908" FT VAR_SEQ 39..98 FT /note="LGSHCVAQTGLELLASGDPLPSASQNAEMIETGSDCVTQAGLQLLASSDPPA FT LASKNAEV -> TGSDCVTQAGLQLLASSDPPALASKNAEVTVETGFHHVSQADIEFLT FT SIDPTASASGSAGI (in isoform 5)" FT /id="VSP_061769" FT VAR_SEQ 98 FT /note="V -> VTETGFHHVSQADIEFLTSIDPTASASGSAGI (in isoform FT 4)" FT /evidence="ECO:0000303|Ref.11" FT /id="VSP_037909" FT MUTAGEN 182 FT /note="R->A,E,K,L: Strongly decreased leucine transport FT activity." FT /evidence="ECO:0000269|PubMed:30867591" FT MUTAGEN 210 FT /note="C->S: Abolishes dimerization, leucine uptake and FT interaction with beta-1 integrins." FT /evidence="ECO:0000269|PubMed:11696247, FT ECO:0000269|PubMed:17724034, ECO:0000269|PubMed:9829974" FT MUTAGEN 234..630 FT /note="Missing: Nearly abolishes leucine transport FT activity." FT /evidence="ECO:0000269|PubMed:30867591" FT MUTAGEN 365 FT /note="N->Q: Impairs both the stability and the trafficking FT of SLC3A2 to the plasma membrane; when associated with FT Q-381; Q-424 and Q-506." FT /evidence="ECO:0000269|PubMed:36028562" FT MUTAGEN 381 FT /note="N->Q: Impairs both the stability and the trafficking FT of SLC3A2 to the plasma membrane; when associated with FT Q-365; Q-424 and Q-506." FT /evidence="ECO:0000269|PubMed:36028562" FT MUTAGEN 424 FT /note="N->Q: Impairs both the stability and the trafficking FT of SLC3A2 to the plasma membrane; when associated with FT Q-365 Q-381 and Q-506." FT /evidence="ECO:0000269|PubMed:36028562" FT MUTAGEN 431 FT /note="C->S: No effect on dimerization, leucine uptake or FT interaction with beta-1 integrins." FT /evidence="ECO:0000269|PubMed:11696247, FT ECO:0000269|PubMed:9829974" FT MUTAGEN 506 FT /note="N->Q: Impairs both the stability and the trafficking FT of SLC3A2 to the plasma membrane; when associated with FT Q-365 Q-381 and Q-424." FT /evidence="ECO:0000269|PubMed:36028562" FT MUTAGEN 532 FT /note="K->E: Strongly decreased leucine transport FT activity." FT /evidence="ECO:0000269|PubMed:30867591" FT CONFLICT 137 FT /note="G -> E (in Ref. 4; AAA35536)" FT /evidence="ECO:0000305" FT CONFLICT 158 FT /note="A -> P (in Ref. 3; AAA51540)" FT /evidence="ECO:0000305" FT CONFLICT 223 FT /note="A -> P (in Ref. 4; AAA35536)" FT /evidence="ECO:0000305" FT CONFLICT 315 FT /note="E -> D (in Ref. 4; AAA35536)" FT /evidence="ECO:0000305" FT CONFLICT 320 FT /note="S -> F (in Ref. 5; AAA35489)" FT /evidence="ECO:0000305" FT CONFLICT 372 FT /note="E -> G (in Ref. 4; AAA35536)" FT /evidence="ECO:0000305" FT CONFLICT 412..413 FT /note="GE -> PQ (in Ref. 4; AAA35536)" FT /evidence="ECO:0000305" FT CONFLICT 465 FT /note="V -> L (in Ref. 4; AAA35536)" FT /evidence="ECO:0000305" FT CONFLICT 481 FT /note="G -> P (in Ref. 4; AAA35536)" FT /evidence="ECO:0000305" FT CONFLICT 549 FT /note="G -> E (in Ref. 5; AAA35489)" FT /evidence="ECO:0000305" FT CONFLICT 609 FT /note="L -> P (in Ref. 4; AAA35536)" FT /evidence="ECO:0000305" FT CONFLICT 612 FT /note="E -> G (in Ref. 4; AAA35536)" FT /evidence="ECO:0000305" FT HELIX 167..173 FT /evidence="ECO:0007829|PDB:7CMI" FT HELIX 178..181 FT /evidence="ECO:0007829|PDB:7CMI" FT HELIX 183..206 FT /evidence="ECO:0007829|PDB:7CMI" FT HELIX 218..220 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 224..227 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 230..234 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 236..238 FT /evidence="ECO:0007829|PDB:7CMI" FT HELIX 241..245 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 248..253 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 257..261 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 265..267 FT /evidence="ECO:0007829|PDB:6S8V" FT TURN 272..274 FT /evidence="ECO:0007829|PDB:7DSK" FT STRAND 275..280 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 282..284 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 287..299 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 303..307 FT /evidence="ECO:0007829|PDB:6S8V" FT TURN 310..313 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 314..316 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 319..321 FT /evidence="ECO:0007829|PDB:2DH3" FT HELIX 323..340 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 344..347 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 350..352 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 356..370 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 375..379 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 385..392 FT /evidence="ECO:0007829|PDB:6S8V" FT TURN 393..395 FT /evidence="ECO:0007829|PDB:7DF1" FT STRAND 399..401 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 403..405 FT /evidence="ECO:0007829|PDB:7DSQ" FT STRAND 406..408 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 412..425 FT /evidence="ECO:0007829|PDB:6S8V" FT TURN 426..428 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 431..433 FT /evidence="ECO:0007829|PDB:7CMI" FT STRAND 437..439 FT /evidence="ECO:0007829|PDB:2DH3" FT HELIX 441..443 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 447..449 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 450..457 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 460..467 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 470..472 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 476..478 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 479..481 FT /evidence="ECO:0007829|PDB:2DH2" FT STRAND 484..486 FT /evidence="ECO:0007829|PDB:2DH2" FT HELIX 493..495 FT /evidence="ECO:0007829|PDB:2DH3" FT HELIX 500..502 FT /evidence="ECO:0007829|PDB:2DH3" FT HELIX 505..507 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 509..513 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 519..530 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 534..538 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 540..543 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 547..549 FT /evidence="ECO:0007829|PDB:7CMI" FT STRAND 550..556 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 558..560 FT /evidence="ECO:0007829|PDB:7CMI" FT STRAND 562..568 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 570..572 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 580..582 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 585..587 FT /evidence="ECO:0007829|PDB:2DH2" FT STRAND 591..603 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 607..610 FT /evidence="ECO:0007829|PDB:6S8V" FT HELIX 611..613 FT /evidence="ECO:0007829|PDB:6S8V" FT STRAND 621..626 FT /evidence="ECO:0007829|PDB:6S8V" FT INIT_MET P08195-2:1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:22223895" FT MOD_RES P08195-2:2 FT /note="N-acetylserine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:22223895" FT MOD_RES P08195-2:2 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" SQ SEQUENCE 630 AA; 67994 MW; AE427F8204CC10B0 CRC64; MELQPPEASI AVVSIPRQLP GSHSEAGVQG LSAGDDSELG SHCVAQTGLE LLASGDPLPS ASQNAEMIET GSDCVTQAGL QLLASSDPPA LASKNAEVTG TMSQDTEVDM KEVELNELEP EKQPMNAASG AAMSLAGAEK NGLVKIKVAE DEAEAAAAAK FTGLSKEELL KVAGSPGWVR TRWALLLLFW LGWLGMLAGA VVIIVRAPRC RELPAQKWWH TGALYRIGDL QAFQGHGAGN LAGLKGRLDY LSSLKVKGLV LGPIHKNQKD DVAQTDLLQI DPNFGSKEDF DSLLQSAKKK SIRVILDLTP NYRGENSWFS TQVDTVATKV KDALEFWLQA GVDGFQVRDI ENLKDASSFL AEWQNITKGF SEDRLLIAGT NSSDLQQILS LLESNKDLLL TSSYLSDSGS TGEHTKSLVT QYLNATGNRW CSWSLSQARL LTSFLPAQLL RLYQLMLFTL PGTPVFSYGD EIGLDAAALP GQPMEAPVML WDESSFPDIP GAVSANMTVK GQSEDPGSLL SLFRRLSDQR SKERSLLHGD FHAFSAGPGL FSYIRHWDQN ERFLVVLNFG DVGLSAGLQA SDLPASASLP AKADLLLSTQ PGREEGSPLE LERLKLEPHE GLLLRFPYAA //