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Protein

Y+L amino acid transporter 2

Gene

SLC7A6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the sodium-independent uptake of dibasic amino acids and sodium-dependent uptake of some neutral amino acids. Requires coexpression with SLC3A2/4F2hc to mediate the uptake of arginine, leucine and glutamine. Also acts as an arginine/glutamine exchanger, following an antiport mechanism for amino acid transport, influencing arginine release in exchange for extracellular amino acids. Plays a role in nitric oxide synthesis in human umbilical vein endothelial cells (HUVECs) via transport of L-arginine. Involved in the transport of L-arginine in monocytes. Reduces uptake of ornithine in retinal pigment epithelial (RPE) cells.8 Publications

Enzyme regulationi

Arginine transport is strongly inhibited by lysine, glutamate, leucine, glutamine, methionine and histidine, in the presence of Na+. Also inhibited by protein kinase C (PKC) and treatment with phorbol-12-myristate-13-acetate (PMA). Mutual inhibition is observed when leucine or glutamine is used as substrate. Inhibition of arginine and leucine uptake also occurs when SLC3A2/4F2hc is either truncated at its C-terminus or mutated at critical residues within the terminal 15 amino acids.

Kineticsi

  1. KM=295 µM for glutamine (in the presence of NaCl)1 Publication
  2. KM=236 µM for leucine (in the presence of NaCl)1 Publication
  3. KM=120 µM for arginine (in the presence of NaCl)1 Publication
  4. KM=138 µM for arginine (in the absence of NaCl)1 Publication

    GO - Molecular functioni

    GO - Biological processi

    • amino acid transmembrane transport Source: GO_Central
    • amino acid transport Source: Reactome
    • blood coagulation Source: Reactome
    • cellular amino acid metabolic process Source: ProtInc
    • ion transport Source: Reactome
    • L-alpha-amino acid transmembrane transport Source: GOC
    • L-amino acid transport Source: GOC
    • leukocyte migration Source: Reactome
    • protein complex assembly Source: ProtInc
    • transmembrane transport Source: Reactome
    • transport Source: ProtInc
    Complete GO annotation...

    Keywords - Biological processi

    Amino-acid transport, Antiport, Transport

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000103064-MONOMER.
    ReactomeiREACT_12560. Basigin interactions.
    REACT_13796. Amino acid transport across the plasma membrane.
    SABIO-RKQ92536.

    Protein family/group databases

    TCDBi2.A.3.8.23. the amino acid-polyamine-organocation (apc) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Y+L amino acid transporter 2
    Alternative name(s):
    Cationic amino acid transporter, y+ system
    Solute carrier family 7 member 6
    y(+)L-type amino acid transporter 2
    Short name:
    Y+LAT2
    Short name:
    y+LAT-2
    Gene namesi
    Name:SLC7A6Imported
    Synonyms:KIAA0245Imported
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:11064. SLC7A6.

    Subcellular locationi

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 4444CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei45 – 6521HelicalSequence AnalysisAdd
    BLAST
    Topological domaini66 – 7813ExtracellularSequence AnalysisAdd
    BLAST
    Transmembranei79 – 9921HelicalSequence AnalysisAdd
    BLAST
    Topological domaini100 – 11415CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei115 – 13521HelicalSequence AnalysisAdd
    BLAST
    Topological domaini136 – 16732ExtracellularSequence AnalysisAdd
    BLAST
    Transmembranei168 – 18821HelicalSequence AnalysisAdd
    BLAST
    Topological domaini189 – 1946CytoplasmicSequence Analysis
    Transmembranei195 – 21521HelicalSequence AnalysisAdd
    BLAST
    Topological domaini216 – 23520ExtracellularSequence AnalysisAdd
    BLAST
    Transmembranei236 – 25621HelicalSequence AnalysisAdd
    BLAST
    Topological domaini257 – 26610CytoplasmicSequence Analysis
    Transmembranei267 – 28721HelicalSequence AnalysisAdd
    BLAST
    Topological domaini288 – 31124ExtracellularSequence AnalysisAdd
    BLAST
    Transmembranei312 – 33221HelicalSequence AnalysisAdd
    BLAST
    Topological domaini333 – 36331CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei364 – 38421HelicalSequence AnalysisAdd
    BLAST
    Topological domaini385 – 3851ExtracellularSequence Analysis
    Transmembranei386 – 40621HelicalSequence AnalysisAdd
    BLAST
    Topological domaini407 – 42519CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei426 – 44621HelicalSequence AnalysisAdd
    BLAST
    Topological domaini447 – 4515ExtracellularSequence Analysis
    Transmembranei452 – 47221HelicalSequence AnalysisAdd
    BLAST
    Topological domaini473 – 51543CytoplasmicSequence AnalysisAdd
    BLAST

    GO - Cellular componenti

    • basolateral plasma membrane Source: UniProtKB-SubCell
    • integral component of plasma membrane Source: ProtInc
    • plasma membrane Source: Reactome
    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA35924.

    Polymorphism and mutation databases

    BioMutaiSLC7A6.
    DMDMi190462822.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 515515Y+L amino acid transporter 2PRO_0000341477Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei30 – 301PhosphoserineBy similarity

    Keywords - PTMi

    Disulfide bond, Phosphoprotein

    Proteomic databases

    MaxQBiQ92536.
    PaxDbiQ92536.
    PRIDEiQ92536.

    PTM databases

    PhosphoSiteiQ92536.

    Expressioni

    Tissue specificityi

    Expressed in normal fibroblasts and those from LPI patients. Also expressed in HUVECs, monocytes, RPE cells, and various carcinoma cell lines.6 Publications

    Gene expression databases

    BgeeiQ92536.
    CleanExiHS_SLC7A6.
    ExpressionAtlasiQ92536. baseline and differential.
    GenevestigatoriQ92536.

    Organism-specific databases

    HPAiHPA050713.

    Interactioni

    Subunit structurei

    Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc.2 Publications

    Protein-protein interaction databases

    BioGridi114519. 9 interactions.
    IntActiQ92536. 1 interaction.
    STRINGi9606.ENSP00000219343.

    Structurei

    3D structure databases

    ProteinModelPortaliQ92536.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0531.
    GeneTreeiENSGT00760000119037.
    HOGENOMiHOG000098892.
    HOVERGENiHBG000476.
    InParanoidiQ92536.
    KOiK13872.
    OMAiSSWDMGD.
    OrthoDBiEOG73BVCR.
    PhylomeDBiQ92536.
    TreeFamiTF313355.

    Family and domain databases

    InterProiIPR002293. AA/rel_permease1.
    [Graphical view]
    PANTHERiPTHR11785. PTHR11785. 1 hit.
    PfamiPF13520. AA_permease_2. 1 hit.
    [Graphical view]
    PIRSFiPIRSF006060. AA_transporter. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Q92536-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MEAREPGRPT PTYHLVPNTS QSQVEEDVSS PPQRSSETMQ LKKEISLLNG
    60 70 80 90 100
    VSLVVGNMIG SGIFVSPKGV LVHTASYGMS LIVWAIGGLF SVVGALCYAE
    110 120 130 140 150
    LGTTITKSGA SYAYILEAFG GFIAFIRLWV SLLVVEPTGQ AIIAITFANY
    160 170 180 190 200
    IIQPSFPSCD PPYLACRLLA AACICLLTFV NCAYVKWGTR VQDTFTYAKV
    210 220 230 240 250
    VALIAIIVMG LVKLCQGHSE HFQDAFEGSS WDMGNLSLAL YSALFSYSGW
    260 270 280 290 300
    DTLNFVTEEI KNPERNLPLA IGISMPIVTL IYILTNVAYY TVLNISDVLS
    310 320 330 340 350
    SDAVAVTFAD QTFGMFSWTI PIAVALSCFG GLNASIFASS RLFFVGSREG
    360 370 380 390 400
    HLPDLLSMIH IERFTPIPAL LFNCTMALIY LIVEDVFQLI NYFSFSYWFF
    410 420 430 440 450
    VGLSVVGQLY LRWKEPKRPR PLKLSVFFPI VFCICSVFLV IVPLFTDTIN
    460 470 480 490 500
    SLIGIGIALS GVPFYFMGVY LPESRRPLFI RNVLAAITRG TQQLCFCVLT
    510
    ELDVAEEKKD ERKTD
    Length:515
    Mass (Da):56,828
    Last modified:June 10, 2008 - v3
    Checksum:i4E92F6E1972351A9
    GO

    Sequence cautioni

    The sequence BAA13376.2 differs from that shown. Reason: Erroneous initiation. Curated

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti8 – 81R → G in CAH18146 (PubMed:17974005).Curated
    Sequence conflicti388 – 3881Q → R in CAH18146 (PubMed:17974005).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    D87432 mRNA. Translation: BAA13376.2. Different initiation.
    CR749291 mRNA. Translation: CAH18146.1.
    CH471092 Genomic DNA. Translation: EAW83219.1.
    BC028216 mRNA. Translation: AAH28216.1.
    CCDSiCCDS32470.1.
    RefSeqiNP_001070253.1. NM_001076785.2.
    NP_003974.3. NM_003983.5.
    UniGeneiHs.679580.

    Genome annotation databases

    EnsembliENST00000219343; ENSP00000219343; ENSG00000103064.
    ENST00000566454; ENSP00000455064; ENSG00000103064.
    GeneIDi9057.
    KEGGihsa:9057.
    UCSCiuc002evt.2. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    D87432 mRNA. Translation: BAA13376.2. Different initiation.
    CR749291 mRNA. Translation: CAH18146.1.
    CH471092 Genomic DNA. Translation: EAW83219.1.
    BC028216 mRNA. Translation: AAH28216.1.
    CCDSiCCDS32470.1.
    RefSeqiNP_001070253.1. NM_001076785.2.
    NP_003974.3. NM_003983.5.
    UniGeneiHs.679580.

    3D structure databases

    ProteinModelPortaliQ92536.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi114519. 9 interactions.
    IntActiQ92536. 1 interaction.
    STRINGi9606.ENSP00000219343.

    Protein family/group databases

    TCDBi2.A.3.8.23. the amino acid-polyamine-organocation (apc) family.

    PTM databases

    PhosphoSiteiQ92536.

    Polymorphism and mutation databases

    BioMutaiSLC7A6.
    DMDMi190462822.

    Proteomic databases

    MaxQBiQ92536.
    PaxDbiQ92536.
    PRIDEiQ92536.

    Protocols and materials databases

    DNASUi9057.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000219343; ENSP00000219343; ENSG00000103064.
    ENST00000566454; ENSP00000455064; ENSG00000103064.
    GeneIDi9057.
    KEGGihsa:9057.
    UCSCiuc002evt.2. human.

    Organism-specific databases

    CTDi9057.
    GeneCardsiGC16P068298.
    H-InvDBHIX0013172.
    HGNCiHGNC:11064. SLC7A6.
    HPAiHPA050713.
    MIMi605641. gene.
    neXtProtiNX_Q92536.
    PharmGKBiPA35924.
    HUGEiSearch...
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG0531.
    GeneTreeiENSGT00760000119037.
    HOGENOMiHOG000098892.
    HOVERGENiHBG000476.
    InParanoidiQ92536.
    KOiK13872.
    OMAiSSWDMGD.
    OrthoDBiEOG73BVCR.
    PhylomeDBiQ92536.
    TreeFamiTF313355.

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000103064-MONOMER.
    ReactomeiREACT_12560. Basigin interactions.
    REACT_13796. Amino acid transport across the plasma membrane.
    SABIO-RKQ92536.

    Miscellaneous databases

    ChiTaRSiSLC7A6. human.
    GeneWikiiSLC7A6.
    GenomeRNAii9057.
    NextBioi33939.
    PROiQ92536.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ92536.
    CleanExiHS_SLC7A6.
    ExpressionAtlasiQ92536. baseline and differential.
    GenevestigatoriQ92536.

    Family and domain databases

    InterProiIPR002293. AA/rel_permease1.
    [Graphical view]
    PANTHERiPTHR11785. PTHR11785. 1 hit.
    PfamiPF13520. AA_permease_2. 1 hit.
    [Graphical view]
    PIRSFiPIRSF006060. AA_transporter. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Identification and characterization of a membrane protein (y+L amino acid transporter-1) that associates with 4F2hc to encode the amino acid transport activity y+L. A candidate gene for lysinuric protein intolerance."
      Torrents D., Estevez R., Pineda M., Fernandez E., Lloberas J., Shi Y.-B., Zorzano A., Palacin M.
      J. Biol. Chem. 273:32437-32445(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
      Tissue: Myoblast1 Publication.
    2. "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain."
      Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N.
      DNA Res. 3:321-329(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Bone marrowImported.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Salivary gland.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: LeukocyteImported.
    6. "Arginine transport through system y(+)L in cultured human fibroblasts: normal phenotype of cells from LPI subjects."
      Dall'Asta V., Bussolati O., Sala R., Rotoli B.M., Sebastio G., Sperandeo M.P., Andria G., Gazzola G.C.
      Am. J. Physiol. 279:C1829-C1837(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    7. "The heterodimeric amino acid transporter 4F2hc/y+LAT2 mediates arginine efflux in exchange with glutamine."
      Broeer A., Wagner C.A., Lang F., Broeer S.
      Biochem. J. 349:787-795(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, INHIBITION.
    8. "Association of 4F2hc with light chains LAT1, LAT2 or y+LAT2 requires different domains."
      Broeer A., Friedrich B., Wagner C.A., Fillon S., Ganapathy V., Lang F., Broeer S.
      Biochem. J. 355:725-731(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT.
    9. "Two-way arginine transport in human endothelial cells: TNF-alpha stimulation is restricted to system y(+)."
      Sala R., Rotoli B.M., Colla E., Visigalli R., Parolari A., Bussolati O., Gazzola G.C., Dall'Asta V.
      Am. J. Physiol. 282:C134-C143(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    10. "Nitric oxide synthesis requires activity of the cationic and neutral amino acid transport system y+L in human umbilical vein endothelium."
      Arancibia-Garavilla Y., Toledo F., Casanello P., Sobrevia L.
      Exp. Physiol. 88:699-710(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.
    11. "INFgamma stimulates arginine transport through system y+L in human monocytes."
      Rotoli B.M., Bussolati O., Sala R., Barilli A., Talarico E., Gazzola G.C., Dall'Asta V.
      FEBS Lett. 571:177-181(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.
    12. "A y(+)LAT-1 mutant protein interferes with y(+)LAT-2 activity: implications for the molecular pathogenesis of lysinuric protein intolerance."
      Sperandeo M.P., Paladino S., Maiuri L., Maroupulos G.D., Zurzolo C., Taglialatela M., Andria G., Sebastio G.
      Eur. J. Hum. Genet. 13:628-634(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    13. "Mutation of the 4F2 heavy-chain carboxy terminus causes y+ LAT2 light-chain dysfunction."
      Chubb S., Kingsland A.L., Broeer A., Broeer S.
      Mol. Membr. Biol. 23:255-267(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, INHIBITION.
    14. "Activation of classical protein kinase C decreases transport via systems y+ and y+L."
      Rotmann A., Simon A., Martine U., Habermeier A., Closs E.I.
      Am. J. Physiol. 292:C2259-C2268(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY, INHIBITION.
    15. "Ornithine transport via cationic amino acid transporter-1 is involved in ornithine cytotoxicity in retinal pigment epithelial cells."
      Kaneko S., Ando A., Okuda-Ashitaka E., Maeda M., Furuta K., Suzuki M., Matsumura M., Ito S.
      Invest. Ophthalmol. Vis. Sci. 48:464-471(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiYLAT2_HUMAN
    AccessioniPrimary (citable) accession number: Q92536
    Secondary accession number(s): Q68DS4, Q7L1N3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 10, 2008
    Last sequence update: June 10, 2008
    Last modified: April 29, 2015
    This is version 121 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.