Q92536 (YLAT2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	SLC7A6
Synonyms:	KIAA0245

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	515 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Amino-acid transport Antiport Transport
Cellular component	Cell membrane Membrane
Domain	Transmembrane Transmembrane helix
PTM	Disulfide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Traceable author statement. Source: Reactome cellular amino acid metabolic process Traceable author statement Ref.1. Source: ProtInc leukocyte migration Traceable author statement. Source: Reactome protein complex assembly Traceable author statement Ref.1. Source: ProtInc
Cellular_component	basolateral plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	amino acid transmembrane transporter activity Traceable author statement Ref.1. Source: ProtInc antiporter activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 515	515	Y+L amino acid transporter 2		PRO_0000341477
Regions
	Topological domain	1 – 44	44	Cytoplasmic Potential
	Transmembrane	45 – 65	21	Helical; Potential
	Topological domain	66 – 78	13	Extracellular Potential
	Transmembrane	79 – 99	21	Helical; Potential
	Topological domain	100 – 114	15	Cytoplasmic Potential
	Transmembrane	115 – 135	21	Helical; Potential
	Topological domain	136 – 167	32	Extracellular Potential
	Transmembrane	168 – 188	21	Helical; Potential
	Topological domain	189 – 194	6	Cytoplasmic Potential
	Transmembrane	195 – 215	21	Helical; Potential
	Topological domain	216 – 235	20	Extracellular Potential
	Transmembrane	236 – 256	21	Helical; Potential
	Topological domain	257 – 266	10	Cytoplasmic Potential
	Transmembrane	267 – 287	21	Helical; Potential
	Topological domain	288 – 311	24	Extracellular Potential
	Transmembrane	312 – 332	21	Helical; Potential
	Topological domain	333 – 363	31	Cytoplasmic Potential
	Transmembrane	364 – 384	21	Helical; Potential
	Topological domain	385	1	Extracellular Potential
	Transmembrane	386 – 406	21	Helical; Potential
	Topological domain	407 – 425	19	Cytoplasmic Potential
	Transmembrane	426 – 446	21	Helical; Potential
	Topological domain	447 – 451	5	Extracellular Potential
	Transmembrane	452 – 472	21	Helical; Potential
	Topological domain	473 – 515	43	Cytoplasmic Potential
Experimental info
	Sequence conflict	8	1	R → G in CAH18146. Ref.3
	Sequence conflict	388	1	Q → R in CAH18146. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q92536 [UniParc]. Last modified June 10, 2008. Version 3. Checksum: 4E92F6E1972351A9	FASTA	515	56,828
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00644701.
RefSeq	NP_001070253.1. NM_001076785.2. NP_003974.3. NM_003983.5.
UniGene	Hs.679580.
3D structure databases
ProteinModelPortal	Q92536.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q92536. 1 interaction.
STRING	9606.ENSP00000219343.
PTM databases
PhosphoSite	Q92536.
Polymorphism databases
DMDM	190462822.
Proteomic databases
PaxDb	Q92536.
PRIDE	Q92536.
Protocols and materials databases
DNASU	9057.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000219343; ENSP00000219343; ENSG00000103064. ENST00000566454; ENSP00000455064; ENSG00000103064.
GeneID	9057.
KEGG	hsa:9057.
UCSC	uc002evt.2. human.
Organism-specific databases
CTD	9057.
GeneCards	GC16P068298.
H-InvDB	HIX0013172.
HGNC	HGNC:11064. SLC7A6.
HPA	HPA050713.
MIM	605641. gene.
neXtProt	NX_Q92536.
PharmGKB	PA35924.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0531.
HOGENOM	HOG000098892.
HOVERGEN	HBG000476.
InParanoid	Q92536.
KO	K13872.
OMA	PTYHLLP.
OrthoDB	EOG4255SN.
PhylomeDB	Q92536.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000103064-MONOMER.
Reactome	REACT_15518. Transmembrane transport of small molecules. REACT_19419. Amino acid and oligopeptide SLC transporters. REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	Q92536.
Bgee	Q92536.
CleanEx	HS_SLC7A6.
Genevestigator	Q92536.
Family and domain databases
InterPro	IPR002293. AA/rel_permease1. [Graphical view]
PANTHER	PTHR11785. PTHR11785. 1 hit.
PIRSF	PIRSF006060. AA_transporter. 1 hit.
PROSITE	PS00218. AMINO_ACID_PERMEASE_1. False negative. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	9057.
NextBio	33939.
SOURCE	Search...

Entry information

Entry name

YLAT2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 104 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.