YLAT2_HUMAN
ID YLAT2_HUMAN Reviewed; 515 AA.
AC Q92536; Q68DS4; Q7L1N3;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 3.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Y+L amino acid transporter 2;
DE AltName: Full=Cationic amino acid transporter, y+ system;
DE AltName: Full=Solute carrier family 7 member 6;
DE AltName: Full=y(+)L-type amino acid transporter 2;
DE Short=Y+LAT2;
DE Short=y+LAT-2;
GN Name=SLC7A6 {ECO:0000312|HGNC:HGNC:11064};
GN Synonyms=KIAA0245 {ECO:0000312|EMBL:BAA13376.2};
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] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Myoblast {ECO:0000269|PubMed:9829974};
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 [2] {ECO:0000312|EMBL:BAA13376.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow {ECO:0000312|EMBL:BAA13376.2};
RX PubMed=9039502; DOI=10.1093/dnares/3.5.321;
RA Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O.,
RA Tanaka A., Kotani H., Miyajima N., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. VI. The
RT coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of
RT cDNA clones from cell line KG-1 and brain.";
RL DNA Res. 3:321-329(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Salivary gland;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4] {ECO:0000312|EMBL:CAH18146.1}
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 [5] {ECO:0000312|EMBL:AAH28216.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Leukocyte {ECO:0000312|EMBL:AAH28216.1};
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 [6] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=11078698; DOI=10.1152/ajpcell.2000.279.6.c1829;
RA Dall'Asta V., Bussolati O., Sala R., Rotoli B.M., Sebastio G.,
RA Sperandeo M.P., Andria G., Gazzola G.C.;
RT "Arginine transport through system y(+)L in cultured human fibroblasts:
RT normal phenotype of cells from LPI subjects.";
RL Am. J. Physiol. 279:C1829-C1837(2000).
RN [7] {ECO:0000305}
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND INHIBITION.
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 [8] {ECO:0000305}
RP FUNCTION, AND SUBUNIT.
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 [9] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=11742806; DOI=10.1152/ajpcell.2002.282.1.c134;
RA Sala R., Rotoli B.M., Colla E., Visigalli R., Parolari A., Bussolati O.,
RA Gazzola G.C., Dall'Asta V.;
RT "Two-way arginine transport in human endothelial cells: TNF-alpha
RT stimulation is restricted to system y(+).";
RL Am. J. Physiol. 282:C134-C143(2002).
RN [10] {ECO:0000305}
RP FUNCTION, 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 [11] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15280038; DOI=10.1016/j.febslet.2004.06.086;
RA Rotoli B.M., Bussolati O., Sala R., Barilli A., Talarico E., Gazzola G.C.,
RA Dall'Asta V.;
RT "INFgamma stimulates arginine transport through system y+L in human
RT monocytes.";
RL FEBS Lett. 571:177-181(2004).
RN [12] {ECO:0000305}
RP SUBCELLULAR LOCATION.
RX PubMed=15756301; DOI=10.1038/sj.ejhg.5201376;
RA Sperandeo M.P., Paladino S., Maiuri L., Maroupulos G.D., Zurzolo C.,
RA Taglialatela M., Andria G., Sebastio G.;
RT "A y(+)LAT-1 mutant protein interferes with y(+)LAT-2 activity:
RT implications for the molecular pathogenesis of lysinuric protein
RT intolerance.";
RL Eur. J. Hum. Genet. 13:628-634(2005).
RN [13] {ECO:0000305}
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND INHIBITION.
RX PubMed=16785209; DOI=10.1080/09687860600652968;
RA Chubb S., Kingsland A.L., Broeer A., Broeer S.;
RT "Mutation of the 4F2 heavy-chain carboxy terminus causes y+ LAT2 light-
RT chain dysfunction.";
RL Mol. Membr. Biol. 23:255-267(2006).
RN [14] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND INHIBITION.
RX PubMed=17329401; DOI=10.1152/ajpcell.00323.2006;
RA Rotmann A., Simon A., Martine U., Habermeier A., Closs E.I.;
RT "Activation of classical protein kinase C decreases transport via systems
RT y+ and y+L.";
RL Am. J. Physiol. 292:C2259-C2268(2007).
RN [15] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=17197568; DOI=10.1167/iovs.06-0398;
RA Kaneko S., Ando A., Okuda-Ashitaka E., Maeda M., Furuta K., Suzuki M.,
RA Matsumura M., Ito S.;
RT "Ornithine transport via cationic amino acid transporter-1 is involved in
RT ornithine cytotoxicity in retinal pigment epithelial cells.";
RL Invest. Ophthalmol. Vis. Sci. 48:464-471(2007).
CC -!- FUNCTION: Involved in the sodium-independent uptake of dibasic amino
CC acids and sodium-dependent uptake of some neutral amino acids. Requires
CC coexpression with SLC3A2/4F2hc to mediate the uptake of arginine,
CC leucine and glutamine. Also acts as an arginine/glutamine exchanger,
CC following an antiport mechanism for amino acid transport, influencing
CC arginine release in exchange for extracellular amino acids. Plays a
CC role in nitric oxide synthesis in human umbilical vein endothelial
CC cells (HUVECs) via transport of L-arginine. Involved in the transport
CC of L-arginine in monocytes. Reduces uptake of ornithine in retinal
CC pigment epithelial (RPE) cells. {ECO:0000269|PubMed:10903140,
CC ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:14603368,
CC ECO:0000269|PubMed:15280038, ECO:0000269|PubMed:16785209,
CC ECO:0000269|PubMed:17197568, ECO:0000269|PubMed:17329401,
CC ECO:0000269|PubMed:9829974}.
CC -!- ACTIVITY REGULATION: Arginine transport is strongly inhibited by
CC lysine, glutamate, leucine, glutamine, methionine and histidine, in the
CC presence of Na(+). Also inhibited by protein kinase C (PKC) and
CC treatment with phorbol-12-myristate-13-acetate (PMA). Mutual inhibition
CC is observed when leucine or glutamine is used as substrate. Inhibition
CC of arginine and leucine uptake also occurs when SLC3A2/4F2hc is either
CC truncated at its C-terminus or mutated at critical residues within the
CC terminal 15 amino acids.
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 the amino acid transport
CC protein SLC3A2/4F2hc. {ECO:0000269|PubMed:11311135,
CC ECO:0000269|PubMed:16785209}.
CC -!- INTERACTION:
CC Q92536; Q9UPQ8: DOLK; NbExp=3; IntAct=EBI-2880595, EBI-8645574;
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000269|PubMed:15756301, ECO:0000269|PubMed:16785209}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:15756301,
CC ECO:0000269|PubMed:16785209}.
CC -!- TISSUE SPECIFICITY: Expressed in normal fibroblasts and those from LPI
CC patients. Also expressed in HUVECs, monocytes, RPE cells, and various
CC carcinoma cell lines. {ECO:0000269|PubMed:11078698,
CC ECO:0000269|PubMed:11742806, ECO:0000269|PubMed:14603368,
CC ECO:0000269|PubMed:15280038, ECO:0000269|PubMed:17197568,
CC ECO:0000269|PubMed:17329401}.
CC -!- SIMILARITY: Belongs to the amino acid-polyamine-organocation (APC)
CC superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family.
CC {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA13376.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; D87432; BAA13376.2; ALT_INIT; mRNA.
DR EMBL; CR749291; CAH18146.1; -; mRNA.
DR EMBL; CH471092; EAW83219.1; -; Genomic_DNA.
DR EMBL; BC028216; AAH28216.1; -; mRNA.
DR CCDS; CCDS32470.1; -.
DR RefSeq; NP_001070253.1; NM_001076785.2.
DR RefSeq; NP_003974.3; NM_003983.5.
DR RefSeq; XP_011521735.1; XM_011523433.1.
DR RefSeq; XP_011521736.1; XM_011523434.1.
DR RefSeq; XP_011521740.1; XM_011523438.1.
DR AlphaFoldDB; Q92536; -.
DR SMR; Q92536; -.
DR BioGRID; 114519; 55.
DR IntAct; Q92536; 4.
DR STRING; 9606.ENSP00000455064; -.
DR DrugBank; DB00130; L-Glutamine.
DR TCDB; 2.A.3.8.23; the amino acid-polyamine-organocation (apc) family.
DR iPTMnet; Q92536; -.
DR PhosphoSitePlus; Q92536; -.
DR BioMuta; SLC7A6; -.
DR DMDM; 190462822; -.
DR EPD; Q92536; -.
DR jPOST; Q92536; -.
DR MassIVE; Q92536; -.
DR MaxQB; Q92536; -.
DR PaxDb; Q92536; -.
DR PeptideAtlas; Q92536; -.
DR PRIDE; Q92536; -.
DR ProteomicsDB; 75294; -.
DR Antibodypedia; 55124; 110 antibodies from 17 providers.
DR DNASU; 9057; -.
DR Ensembl; ENST00000219343.11; ENSP00000219343.6; ENSG00000103064.15.
DR Ensembl; ENST00000566454.5; ENSP00000455064.1; ENSG00000103064.15.
DR GeneID; 9057; -.
DR KEGG; hsa:9057; -.
DR MANE-Select; ENST00000219343.11; ENSP00000219343.6; NM_003983.6; NP_003974.3.
DR UCSC; uc002evt.3; human.
DR CTD; 9057; -.
DR DisGeNET; 9057; -.
DR GeneCards; SLC7A6; -.
DR HGNC; HGNC:11064; SLC7A6.
DR HPA; ENSG00000103064; Tissue enhanced (skeletal).
DR MIM; 605641; gene.
DR neXtProt; NX_Q92536; -.
DR OpenTargets; ENSG00000103064; -.
DR PharmGKB; PA35924; -.
DR VEuPathDB; HostDB:ENSG00000103064; -.
DR eggNOG; KOG1287; Eukaryota.
DR GeneTree; ENSGT00940000158295; -.
DR HOGENOM; CLU_007946_3_0_1; -.
DR InParanoid; Q92536; -.
DR OMA; QIVFRRR; -.
DR OrthoDB; 621852at2759; -.
DR PhylomeDB; Q92536; -.
DR TreeFam; TF313355; -.
DR BioCyc; MetaCyc:ENSG00000103064-MON; -.
DR PathwayCommons; Q92536; -.
DR Reactome; R-HSA-210991; Basigin interactions.
DR Reactome; R-HSA-352230; Amino acid transport across the plasma membrane.
DR SABIO-RK; Q92536; -.
DR SignaLink; Q92536; -.
DR BioGRID-ORCS; 9057; 23 hits in 1076 CRISPR screens.
DR ChiTaRS; SLC7A6; human.
DR GeneWiki; SLC7A6; -.
DR GenomeRNAi; 9057; -.
DR Pharos; Q92536; Tbio.
DR PRO; PR:Q92536; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q92536; protein.
DR Bgee; ENSG00000103064; Expressed in apex of heart and 169 other tissues.
DR ExpressionAtlas; Q92536; baseline and differential.
DR Genevisible; Q92536; HS.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; TAS:ProtInc.
DR GO; GO:0015297; F:antiporter activity; IEA:UniProtKB-KW.
DR GO; GO:0015174; F:basic amino acid transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0015179; F:L-amino acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0003333; P:amino acid transmembrane transport; TAS:GO_Central.
DR GO; GO:0015822; P:ornithine transport; IMP:ARUK-UCL.
DR InterPro; IPR002293; AA/rel_permease1.
DR Pfam; PF13520; AA_permease_2; 1.
PE 1: Evidence at protein level;
KW Amino-acid transport; Antiport; Cell membrane; Disulfide bond; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..515
FT /note="Y+L amino acid transporter 2"
FT /id="PRO_0000341477"
FT TOPO_DOM 1..44
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 45..65
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 66..78
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 79..99
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 100..114
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 115..135
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 136..167
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..188
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 189..194
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 195..215
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 216..235
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 236..256
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 257..266
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 267..287
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 288..311
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 312..332
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 333..363
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 364..384
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 385
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 386..406
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 407..425
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 426..446
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 447..451
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 452..472
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 473..515
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 13..36
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 30
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BGK6"
FT CONFLICT 8
FT /note="R -> G (in Ref. 3; CAH18146)"
FT /evidence="ECO:0000305"
FT CONFLICT 388
FT /note="Q -> R (in Ref. 3; CAH18146)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 515 AA; 56828 MW; 4E92F6E1972351A9 CRC64;
MEAREPGRPT PTYHLVPNTS QSQVEEDVSS PPQRSSETMQ LKKEISLLNG VSLVVGNMIG
SGIFVSPKGV LVHTASYGMS LIVWAIGGLF SVVGALCYAE LGTTITKSGA SYAYILEAFG
GFIAFIRLWV SLLVVEPTGQ AIIAITFANY IIQPSFPSCD PPYLACRLLA AACICLLTFV
NCAYVKWGTR VQDTFTYAKV VALIAIIVMG LVKLCQGHSE HFQDAFEGSS WDMGNLSLAL
YSALFSYSGW DTLNFVTEEI KNPERNLPLA IGISMPIVTL IYILTNVAYY TVLNISDVLS
SDAVAVTFAD QTFGMFSWTI PIAVALSCFG GLNASIFASS RLFFVGSREG HLPDLLSMIH
IERFTPIPAL LFNCTMALIY LIVEDVFQLI NYFSFSYWFF VGLSVVGQLY LRWKEPKRPR
PLKLSVFFPI VFCICSVFLV IVPLFTDTIN SLIGIGIALS GVPFYFMGVY LPESRRPLFI
RNVLAAITRG TQQLCFCVLT ELDVAEEKKD ERKTD
