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Q92536 (YLAT2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SLC7A6
Synonyms:KIAA0245
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length515 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.7 Ref.8 Ref.10 Ref.11 Ref.13 Ref.14 Ref.15

Enzyme regulation

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.

Subunit structure

Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc. Ref.8 Ref.13

Subcellular location

Basolateral cell membrane; Multi-pass membrane protein Ref.12 Ref.13.

Tissue specificity

Expressed in normal fibroblasts and those from LPI patients. Also expressed in HUVECs, monocytes, RPE cells, and various carcinoma cell lines. Ref.6 Ref.9 Ref.10 Ref.11 Ref.14 Ref.15

Sequence similarities

Belongs to the amino acid-polyamine-organocation (APC) superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family. [View classification]

Biophysicochemical properties

Kinetic parameters:

KM=295 µM for glutamine (in the presence of NaCl) Ref.7

KM=236 µM for leucine (in the presence of NaCl) Ref.7

KM=120 µM for arginine (in the presence of NaCl) Ref.7

KM=138 µM for arginine (in the absence of NaCl) Ref.7

Sequence caution

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 515515Y+L amino acid transporter 2
PRO_0000341477

Regions

Topological domain1 – 4444Cytoplasmic Potential
Transmembrane45 – 6521Helical; Potential
Topological domain66 – 7813Extracellular Potential
Transmembrane79 – 9921Helical; Potential
Topological domain100 – 11415Cytoplasmic Potential
Transmembrane115 – 13521Helical; Potential
Topological domain136 – 16732Extracellular Potential
Transmembrane168 – 18821Helical; Potential
Topological domain189 – 1946Cytoplasmic Potential
Transmembrane195 – 21521Helical; Potential
Topological domain216 – 23520Extracellular Potential
Transmembrane236 – 25621Helical; Potential
Topological domain257 – 26610Cytoplasmic Potential
Transmembrane267 – 28721Helical; Potential
Topological domain288 – 31124Extracellular Potential
Transmembrane312 – 33221Helical; Potential
Topological domain333 – 36331Cytoplasmic Potential
Transmembrane364 – 38421Helical; Potential
Topological domain3851Extracellular Potential
Transmembrane386 – 40621Helical; Potential
Topological domain407 – 42519Cytoplasmic Potential
Transmembrane426 – 44621Helical; Potential
Topological domain447 – 4515Extracellular Potential
Transmembrane452 – 47221Helical; Potential
Topological domain473 – 51543Cytoplasmic Potential

Amino acid modifications

Modified residue301Phosphoserine By similarity

Experimental info

Sequence conflict81R → G in CAH18146. Ref.3
Sequence conflict3881Q → R in CAH18146. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q92536 [UniParc].

Last modified June 10, 2008. Version 3.
Checksum: 4E92F6E1972351A9

FASTA51556,828
        10         20         30         40         50         60 
MEAREPGRPT PTYHLVPNTS QSQVEEDVSS PPQRSSETMQ LKKEISLLNG VSLVVGNMIG 

        70         80         90        100        110        120 
SGIFVSPKGV LVHTASYGMS LIVWAIGGLF SVVGALCYAE LGTTITKSGA SYAYILEAFG 

       130        140        150        160        170        180 
GFIAFIRLWV SLLVVEPTGQ AIIAITFANY IIQPSFPSCD PPYLACRLLA AACICLLTFV 

       190        200        210        220        230        240 
NCAYVKWGTR VQDTFTYAKV VALIAIIVMG LVKLCQGHSE HFQDAFEGSS WDMGNLSLAL 

       250        260        270        280        290        300 
YSALFSYSGW DTLNFVTEEI KNPERNLPLA IGISMPIVTL IYILTNVAYY TVLNISDVLS 

       310        320        330        340        350        360 
SDAVAVTFAD QTFGMFSWTI PIAVALSCFG GLNASIFASS RLFFVGSREG HLPDLLSMIH 

       370        380        390        400        410        420 
IERFTPIPAL LFNCTMALIY LIVEDVFQLI NYFSFSYWFF VGLSVVGQLY LRWKEPKRPR 

       430        440        450        460        470        480 
PLKLSVFFPI VFCICSVFLV IVPLFTDTIN SLIGIGIALS GVPFYFMGVY LPESRRPLFI 

       490        500        510 
RNVLAAITRG TQQLCFCVLT ELDVAEEKKD ERKTD 

« Hide

References

« Hide 'large scale' references
[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: Myoblast.
[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 marrow.
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Salivary gland.
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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: Leukocyte.
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D87432 mRNA. Translation: BAA13376.2. Different initiation.
CR749291 mRNA. Translation: CAH18146.1.
CH471092 Genomic DNA. Translation: EAW83219.1.
BC028216 mRNA. Translation: AAH28216.1.
RefSeqNP_001070253.1. NM_001076785.2.
NP_003974.3. NM_003983.5.
UniGeneHs.679580.

3D structure databases

ProteinModelPortalQ92536.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ92536. 1 interaction.
STRING9606.ENSP00000219343.

Protein family/group databases

TCDB2.A.3.8.23. the amino acid-polyamine-organocation (apc) family.

PTM databases

PhosphoSiteQ92536.

Polymorphism databases

DMDM190462822.

Proteomic databases

PaxDbQ92536.
PRIDEQ92536.

Protocols and materials databases

DNASU9057.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000219343; ENSP00000219343; ENSG00000103064.
ENST00000566454; ENSP00000455064; ENSG00000103064.
GeneID9057.
KEGGhsa:9057.
UCSCuc002evt.2. human.

Organism-specific databases

CTD9057.
GeneCardsGC16P068298.
H-InvDBHIX0013172.
HGNCHGNC:11064. SLC7A6.
HPAHPA050713.
MIM605641. gene.
neXtProtNX_Q92536.
PharmGKBPA35924.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0531.
HOGENOMHOG000098892.
HOVERGENHBG000476.
InParanoidQ92536.
KOK13872.
OMAFCICSLF.
OrthoDBEOG73BVCR.
PhylomeDBQ92536.
TreeFamTF313355.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000103064-MONOMER.
ReactomeREACT_15518. Transmembrane transport of small molecules.
REACT_19419. Amino acid and oligopeptide SLC transporters.
REACT_604. Hemostasis.
SABIO-RKQ92536.

Gene expression databases

ArrayExpressQ92536.
BgeeQ92536.
CleanExHS_SLC7A6.
GenevestigatorQ92536.

Family and domain databases

InterProIPR002293. AA/rel_permease1.
[Graphical view]
PANTHERPTHR11785. PTHR11785. 1 hit.
PfamPF13520. AA_permease_2. 1 hit.
[Graphical view]
PIRSFPIRSF006060. AA_transporter. 1 hit.
ProtoNetSearch...

Other

GeneWikiSLC7A6.
GenomeRNAi9057.
NextBio33939.
PROQ92536.
SOURCESearch...

Entry information

Entry nameYLAT2_HUMAN
AccessionPrimary (citable) accession number: Q92536
Secondary accession number(s): Q68DS4, Q7L1N3
Entry history
Integrated into UniProtKB/Swiss-Prot: June 10, 2008
Last sequence update: June 10, 2008
Last modified: April 16, 2014
This is version 112 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM