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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

  1. amino acid transmembrane transporter activity Source: ProtInc
  2. antiporter activity Source: UniProtKB-KW

GO - Biological processi

  1. amino acid transport Source: Reactome
  2. blood coagulation Source: Reactome
  3. cellular amino acid metabolic process Source: ProtInc
  4. ion transport Source: Reactome
  5. leukocyte migration Source: Reactome
  6. protein complex assembly Source: ProtInc
  7. transmembrane transport Source: Reactome
  8. 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

Basolateral cell membrane 2 Publications; Multi-pass membrane protein 2 Publications

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

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

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35924.

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

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 9, 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.

Polymorphism databases

DMDMi190462822.

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

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 databases

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(1997) [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(1995) [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(2003) [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(1999) [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(1999) [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(2000) [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(2001) [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(2002) [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(2003) [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(2004) [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(2005) [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(2006) [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(2006) [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 9, 2008
Last sequence update: June 9, 2008
Last modified: March 3, 2015
This is version 120 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.