4F2_HUMAN
ID 4F2_HUMAN Reviewed; 630 AA.
AC P08195; Q13543;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-SEP-2009, sequence version 3.
DT 03-AUG-2022, entry version 237.
DE RecName: 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 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 [9]
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 [10]
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 [11]
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 [12]
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 [13]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
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 [14]
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 [15]
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 [16]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
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 [17]
RP FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, AND INTERACTION WITH
RP 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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
RP FUNCTION.
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 [25]
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 [26]
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 [27]
RP FUNCTION, 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 [28]
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 [29]
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 [30]
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 [31]
RP FUNCTION.
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 [32]
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 [33]
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 [34]
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 [35]
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 [36]
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 [37]
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 [38]
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 [39]
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 [40]
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 [41]
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 [42]
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 [43]
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 [44]
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 [45]
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 [46]
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 [47]
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 [48]
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 [49]
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 [50]
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 [51]
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 [52]
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 [53] {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-424; ASN-365; ASN-381;
RP ASN-424 AND ASN-506, DISULFIDE BOND, AND MUTAGENESIS OF ARG-182;
RP 234-GLN--ALA-630 AND 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).
CC -!- FUNCTION: Component of several heterodimeric complexes involved in
CC amino acid transport (PubMed:11557028, PubMed:9829974, PubMed:9751058,
CC PubMed:10391915, PubMed:10574970, PubMed:11311135, PubMed:30341327).
CC The precise substrate specificity depends on the other subunit in the
CC heterodimer (PubMed:9829974, PubMed:9751058, PubMed:10391915,
CC PubMed:10574970, PubMed:30867591, PubMed:10903140). The complexes
CC function as amino acid exchangers (PubMed:11557028, PubMed:10903140,
CC PubMed:12117417, PubMed:12225859, PubMed:30867591). The homodimer
CC functions as sodium-independent, high-affinity transporter that
CC mediates uptake of large neutral amino acids such as phenylalanine,
CC tyrosine, L-DOPA, leucine, histidine, methionine and tryptophan
CC (PubMed:9751058, PubMed:11557028, PubMed:11311135, PubMed:11564694,
CC PubMed:12117417, PubMed:12225859, PubMed:25998567, PubMed:30867591).
CC The heterodimer formed by SLC3A2 and SLC7A6 or SLC3A2 and SLC7A7
CC mediates the uptake of dibasic amino acids (PubMed:9829974,
CC PubMed:10903140). The heterodimer with SLC7A5/LAT1 mediates the
CC transport of thyroid hormones triiodothyronine (T3) and thyroxine (T4)
CC across the cell membrane (PubMed:11564694, PubMed:12225859). The
CC heterodimer with SLC7A5/LAT1 is involved in the uptake of toxic
CC methylmercury (MeHg) when administered as the L-cysteine or D,L-
CC homocysteine complexes (PubMed:12117417). The heterodimer with
CC SLC7A5/LAT1 is involved in the uptake of leucine (PubMed:25998567,
CC PubMed:30341327). When associated with LAPTM4B, the heterodimer with
CC SLC7A5/LAT1 is recruited to lysosomes to promote leucine uptake into
CC these organelles, and thereby mediates mTORC1 activation
CC (PubMed:25998567). The heterodimer with SLC7A5/LAT1 may play a role in
CC the transport of L-DOPA across the blood-brain barrier (By similarity).
CC The heterodimer formed by SLC3A2 and SLC7A5/LAT1 or SLC3A2 and
CC SLC7A8/LAT2 is involved in the cellular activity of small molecular
CC weight nitrosothiols, via the stereoselective transport of L-
CC nitrosocysteine (L-CNSO) across the transmembrane (PubMed:15769744).
CC Together with ICAM1, regulates the transport activity of SLC7A8/LAT2 in
CC polarized intestinal cells by generating and delivering intracellular
CC signals (PubMed:12716892). Required for targeting of SLC7A5/LAT1 and
CC SLC7A8/LAT2 to the plasma membrane and for channel activity
CC (PubMed:9751058, PubMed:11311135, PubMed:30867591). Plays a role in
CC nitric oxide synthesis in human umbilical vein endothelial cells
CC (HUVECs) via transport of L-arginine (PubMed:14603368). May mediate
CC blood-to-retina L-leucine transport across the inner blood-retinal
CC barrier (By similarity). {ECO:0000250|UniProtKB:P10852,
CC ECO:0000250|UniProtKB:Q794F9, ECO:0000269|PubMed:10391915,
CC ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:10903140,
CC ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679,
CC ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:12117417,
CC ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:12716892,
CC ECO:0000269|PubMed:14603368, ECO:0000269|PubMed:15769744,
CC ECO:0000269|PubMed:15980244, ECO:0000269|PubMed:25998567,
CC ECO:0000269|PubMed:30341327, ECO:0000269|PubMed:30867591,
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=295 uM for glutamine (in the presence of NaCl)
CC {ECO:0000269|PubMed:10903140};
CC KM=236 uM for leucine (in the presence of NaCl)
CC {ECO:0000269|PubMed:10903140};
CC KM=120 uM for arginine (in the presence of NaCl)
CC {ECO:0000269|PubMed:10903140};
CC KM=138 uM for arginine (in the absence of NaCl)
CC {ECO:0000269|PubMed:10903140};
CC -!- SUBUNIT: Disulfide-linked heterodimer with a non-glycosylated light
CC chain (SLC7A5/LAT1, SLC7A6, SLCA7A7, SLC7A8/LAT2, SLC7A10 or SLCA7A11)
CC (PubMed:11557028, PubMed:9829974, PubMed:9751058, PubMed:10391915,
CC PubMed:10574970, PubMed:10903140,PubMed:11311135, PubMed:30867591).
CC Interacts with TLCD3A/CT120 (PubMed:12270127). Interacts with ICAM1
CC (PubMed:12716892). Constitutively and specifically associates with
CC beta-1 integrins (alpha-2/beta-1, alpha-3/beta-1, alpha-5/beta-1 and
CC alpha-6/beta-1), but minimally with alpha-4/beta-1 (PubMed:11696247).
CC Interacts with LAPTM4B; recruits SLC3A2 and SLC7A5/LAT1 to lysosomes to
CC promote leucine uptake into these organelles and is required for mTORC1
CC activation (PubMed:25998567). {ECO:0000269|PubMed:10391915,
CC ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:10903140,
CC ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679,
CC ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:11696247, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:12270127, ECO:0000269|PubMed:12716892,
CC ECO:0000269|PubMed:14603368, ECO:0000269|PubMed:17724034,
CC ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30867591,
CC ECO:0000269|PubMed:9751058, ECO:0000269|PubMed:9829974,
CC 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:10391915, ECO:0000269|PubMed:10574970,
CC ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679,
CC ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859,
CC ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:16496379,
CC ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:3476959,
CC ECO:0000269|PubMed:3480538, ECO:0000269|PubMed:9751058,
CC ECO:0000269|PubMed:9829974}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:30867591}. Cell junction
CC {ECO:0000250|UniProtKB:P10852}. Lysosome membrane
CC {ECO:0000269|PubMed:25998567}. Melanosome
CC {ECO:0000269|PubMed:17081065}. 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, ECO:0000269|PubMed:11311135,
CC ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:17081065,
CC ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:9751058}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
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 -!- 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). {ECO:0000269|PubMed:11742812,
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: 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 -!- MISCELLANEOUS: Arginine uptake is inhibited by increasing
CC concentrations of leucine in the presence of Na(+).
CC -!- SIMILARITY: Belongs to the SLC3A transporter family. {ECO:0000305}.
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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; BC001061; AAH01061.2; -; mRNA.
DR EMBL; BC003000; AAH03000.2; -; mRNA.
DR EMBL; BE794697; -; NOT_ANNOTATED_CDS; mRNA.
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.
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; 7P9U; EM; 3.70 A; A=2-630.
DR PDB; 7P9V; EM; 3.40 A; A=2-630.
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; 7P9U; -.
DR PDBsum; 7P9V; -.
DR AlphaFoldDB; P08195; -.
DR SMR; P08195; -.
DR BioGRID; 112411; 355.
DR CORUM; P08195; -.
DR IntAct; P08195; 107.
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 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; P08195; -.
DR PeptideAtlas; P08195; -.
DR PRIDE; P08195; -.
DR ProteomicsDB; 52082; -. [P08195-1]
DR ProteomicsDB; 52083; -. [P08195-2]
DR ProteomicsDB; 52084; -. [P08195-3]
DR ProteomicsDB; 52085; -. [P08195-4]
DR ABCD; P08195; 54 sequenced antibodies.
DR Antibodypedia; 15042; 1043 antibodies from 46 providers.
DR DNASU; 6520; -.
DR Ensembl; ENST00000338663.12; ENSP00000340815.7; ENSG00000168003.18. [P08195-2]
DR Ensembl; ENST00000377889.6; ENSP00000367121.2; ENSG00000168003.18. [P08195-3]
DR Ensembl; ENST00000377890.6; ENSP00000367122.2; ENSG00000168003.18. [P08195-1]
DR Ensembl; ENST00000538084.2; ENSP00000440001.2; ENSG00000168003.18. [P08195-4]
DR Ensembl; ENST00000544377.2; ENSP00000442135.2; ENSG00000168003.18. [P08195-2]
DR Ensembl; ENST00000680631.1; ENSP00000506006.1; ENSG00000168003.18. [P08195-2]
DR Ensembl; ENST00000681657.1; ENSP00000505110.1; ENSG00000168003.18. [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 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; 1384693at2759; -.
DR PhylomeDB; P08195; -.
DR BioCyc; MetaCyc:ENSG00000168003-MON; -.
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 BioGRID-ORCS; 6520; 186 hits in 1091 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 204 other tissues.
DR ExpressionAtlas; P08195; baseline and differential.
DR Genevisible; P08195; HS.
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:0016021; C:integral component of membrane; NAS: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:UniProtKB.
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: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:0015175; F:neutral amino acid transmembrane transporter activity; IGI:ARUK-UCL.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
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:1904273; P:L-alanine import across plasma membrane; IGI:ARUK-UCL.
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; IMP:UniProtKB.
DR GO; GO:0015823; P:phenylalanine transport; IGI:ARUK-UCL.
DR GO; GO:0043330; P:response to exogenous dsRNA; IMP:MGI.
DR GO; GO:0015827; P:tryptophan transport; ISS:UniProtKB.
DR GO; GO:0046718; P:viral entry into host cell; IMP:UniProtKB.
DR Gene3D; 2.60.40.1180; -; 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; PTHR46673; 1.
DR Pfam; PF00128; Alpha-amylase; 1.
DR Pfam; PF16028; SLC3A2_N; 1.
DR SMART; SM00642; Aamy; 1.
DR SUPFAM; SSF51445; SSF51445; 1.
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; Isopeptide bond; Lysosome; Membrane; Phosphoprotein;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW Transport; Ubl conjugation.
FT CHAIN 1..630
FT /note="4F2 cell-surface antigen heavy chain"
FT /id="PRO_0000064383"
FT TOPO_DOM 102..184
FT /note="Cytoplasmic"
FT /evidence="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: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.9, 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:0007744|PDB:6IRS"
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:0007744|PDB:6IRS"
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:0007744|PDB:6IRS"
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:0007744|PDB:6IRS"
FT DISULFID 210
FT /note="Interchain (with C-164 in SLC7A5)"
FT /evidence="ECO:0000269|PubMed:30867591,
FT ECO:0000305|PubMed:17724034"
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 98
FT /note="V -> VTETGFHHVSQADIEFLTSIDPTASASGSAGI (in isoform
FT 4)"
FT /evidence="ECO:0000303|Ref.10"
FT /id="VSP_037909"
FT MUTAGEN 182
FT /note="R->A,E,K,L: Strongly decreased transport 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 transport activity."
FT /evidence="ECO:0000269|PubMed:30867591"
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 532
FT /note="K->E: Strongly decreased transport 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 168..173
FT /evidence="ECO:0007829|PDB:7P9V"
FT TURN 176..178
FT /evidence="ECO:0007829|PDB:7P9V"
FT HELIX 181..206
FT /evidence="ECO:0007829|PDB:6JMQ"
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 TURN 236..238
FT /evidence="ECO:0007829|PDB:7P9V"
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 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 STRAND 399..401
FT /evidence="ECO:0007829|PDB:6S8V"
FT HELIX 403..405
FT /evidence="ECO:0007829|PDB:7P9V"
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 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 550..556
FT /evidence="ECO:0007829|PDB:6S8V"
FT STRAND 558..560
FT /evidence="ECO:0007829|PDB:6JMQ"
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
