Q9UHI5 (LAT2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Large neutral amino acids transporter small subunit 2

Alternative name(s):
L-type amino acid transporter 2
Short name=hLAT2
Solute carrier family 7 member 8

Gene names

Name:	SLC7A8
Synonyms:	LAT2

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	535 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Sodium-independent, high-affinity transport of small and large neutral amino acids such as alanine, serine, threonine, cysteine, phenylalanine, tyrosine, leucine, arginine and tryptophan, when associated with SLC3A2/4F2hc. Acts as an amino acid exchanger. Has higher affinity for L-phenylalanine than LAT1 but lower affinity for glutamine and serine. L-alanine is transported at physiological concentrations. Plays a role in basolateral (re)absorption of neutral amino acids. Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity. Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane. Plays an essential role in the reabsorption of neutral amino acids from the epithelial cells to the bloodstream in the kidney. Ref.1 Ref.2 Ref.4 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13
Subunit structure	Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc. Ref.1 Ref.2 Ref.4 Ref.8 Ref.10 Ref.13
Subcellular location	Cytoplasm. Basolateral cell membrane; Multi-pass membrane protein. Note: Localized to the cytoplasm when expressed alone but when coexpressed with SLC3A2/4F2hc, is localized to the plasma membrane. Colocalized with SLC3A2/4F2hc at the basolateral membrane of kidney cortex proximal tubules and small intestine epithelia of the villi. Ref.1 Ref.4 Ref.12
Tissue specificity	Strongest expression is observed in kidney and moderate expression in placenta and brain, followed by liver, prostate, testis, ovary, lymph node, thymus, spleen, skeletal muscle and heart. Also expressed in fetal liver as well as in the retinal pigment epithelial cell line ARPE-19 and the intestinal epithelial cell line Caco-2. Ref.1 Ref.4 Ref.11 Ref.12
Induction	Activity in polarized intestinal cells is regulated by the association between SLC3A2/4F2 (in the SLC3A2/4F2-LAT2 heterodimer) and ICAM1. Ref.10
Miscellaneous	L-leucine transport activity inhibited by small zwitterionic amino acids (i.e. glycine, alanine, serine, threonine asparginine, glutamine, methionine, leucine, isoleucine, valine, phenylalanine, tyrosine, tryptophan, histidine and cysteine) and by glutamine and asparginine. Methionine uptake was inhibited by the L-system substrates L-leucine, 2-amino-bicyclo-(2,2,1)-heptane-2-carboxylate (BCH), L-cysteine and by the MeHg-L-cysteine complex and structurally related S-ethyl-L-cysteine. MeHg-L-cysteine uptake is inhibited by L-methionine, L-leucine, BCH and S-ethyl-L-cysteine. L-leucine uptake was inhibited by L-CNSO.
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=221 µM for L-leucine Ref.1 Ref.4 Ref.9 Ref.11 KM=64 µM for MeHg-L-cysteine KM=161 µM for methionine KM=978 µM for L-alanine KM=89.35 µM for L-phenylalanine KM=57.3 µM for L-tryptophan KM=48.8 µM for L-tyrosine

Ontologies

Keywords
Biological process	Amino-acid transport Transport
Cellular component	Cell membrane Cytoplasm 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 metal ion homeostasis Non-traceable author statement Ref.8. Source: UniProtKB response to toxin Non-traceable author statement Ref.8. Source: UniProtKB
Cellular_component	basolateral plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	L-amino acid transmembrane transporter activity Inferred from electronic annotation. Source: Compara neutral amino acid transmembrane transporter activity Traceable author statement Ref.1. Source: ProtInc organic cation transmembrane transporter activity Inferred from direct assay Ref.9. Source: UniProtKB peptide antigen binding Inferred from sequence or structural similarity. Source: UniProtKB toxin transporter activity Inferred from direct assay Ref.9. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 535	535	Large neutral amino acids transporter small subunit 2		PRO_0000054273
Regions
	Transmembrane	40 – 60	21	Helical; Potential
	Transmembrane	72 – 92	21	Helical; Potential
	Transmembrane	113 – 133	21	Helical; Potential
	Transmembrane	155 – 175	21	Helical; Potential
	Transmembrane	189 – 209	21	Helical; Potential
	Transmembrane	231 – 251	21	Helical; Potential
	Transmembrane	268 – 288	21	Helical; Potential
	Transmembrane	310 – 330	21	Helical; Potential
	Transmembrane	362 – 382	21	Helical; Potential
	Transmembrane	388 – 408	21	Helical; Potential
	Transmembrane	424 – 444	21	Helical; Potential
	Transmembrane	447 – 467	21	Helical; Potential
Experimental info
	Sequence conflict	225	1	N → D in CAB40137. Ref.3
	Sequence conflict	401	1	V → G in CAB40137. Ref.3
	Sequence conflict	503	1	G → R in AAF05696. Ref.1
	Sequence conflict	503	1	G → R in AAF05697. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9UHI5 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: AC129146353F1E47	FASTA	535	58,382
	10 20 30 40 50 60 MEEGARHRNN TEKKHPGGGE SDASPEAGSG GGGVALKKEI GLVSACGIIV GNIIGSGIFV 70 80 90 100 110 120 SPKGVLENAG SVGLALIVWI VTGFITVVGA LCYAELGVTI PKSGGDYSYV KDIFGGLAGF 130 140 150 160 170 180 LRLWIAVLVI YPTNQAVIAL TFSNYVLQPL FPTCFPPESG LRLLAAICLL LLTWVNCSSV 190 200 210 220 230 240 RWATRVQDIF TAGKLLALAL IIIMGIVQIC KGEYFWLEPK NAFENFQEPD IGLVALAFLQ 250 260 270 280 290 300 GSFAYGGWNF LNYVTEELVD PYKNLPRAIF ISIPLVTFVY VFANVAYVTA MSPQELLASN 310 320 330 340 350 360 AVAVTFGEKL LGVMAWIMPI SVALSTFGGV NGSLFTSSRL FFAGAREGHL PSVLAMIHVK 370 380 390 400 410 420 RCTPIPALLF TCISTLLMLV TSDMYTLINY VGFINYLFYG VTVAGQIVLR WKKPDIPRPI 430 440 450 460 470 480 KINLLFPIIY LLFWAFLLVF SLWSEPVVCG IGLAIMLTGV PVYFLGVYWQ HKPKCFSDFI 490 500 510 520 530 ELLTLVSQKM CVVVYPEVER GSGTEEANED MEEQQQPMYQ PTPTKDKDVA GQPQP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a membrane protein, LAT-2, that co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids." Pineda M., Fernandez E., Torrents D., Estevez R., Lopez C., Camps M., Lloberas J., Zorzano A., Palacin M. J. Biol. Chem. 274:19738-19744(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INHIBITION.
[2]	"LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine." Rossier G., Meier C., Bauch C., Summa V., Sordat B., Verrey F., Kuehn L.C. J. Biol. Chem. 274:34948-34954(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT. Tissue: Melanocyte.
[3]	"SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance." Borsani G., Bassi M.T., Sperandeo M.P., De Grandi A., Buoninconti A., Riboni M., Manzoni M., Incerti B., Pepe A., Andria G., Ballabio A., Sebastio G. Nat. Genet. 21:297-301(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[4]	"Reabsorption of neutral amino acids mediated by amino acid transporter LAT2 and TAT1 in the basolateral membrane of proximal tubule." Park S.Y., Kim J.-K., Kim I.J., Choi B.K., Jung K.Y., Lee S., Park K.J., Chairoungdua A., Kanai Y., Endou H., Kim D.K. Arch. Pharm. Res. 28:421-432(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INHIBITION. Tissue: Kidney.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Hippocampus.
[6]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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: Skin.
[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]	"Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2." Simmons-Willis T.A., Koh A.S., Clarkson T.W., Ballatori N. Biochem. J. 367:239-246(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, INHIBITION.
[10]	"CD98 and intracellular adhesion molecule I regulate the activity of amino acid transporter LAT-2 in polarized intestinal epithelia." Liu X., Charrier L., Gewirtz A., Sitaraman S., Merlin D. J. Biol. Chem. 278:23672-23677(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, INDUCTION.
[11]	"Identification and functional characterization of a Na(+)-independent large neutral amino acid transporter (LAT2) on ARPE-19 cells." Gandhi M.D., Pal D., Mitra A.K. Int. J. Pharm. 275:189-200(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, INHIBITION.
[12]	"Expression of LAT1 and LAT2 amino acid transporters in human and rat intestinal epithelial cells." Fraga S., Pinho M.J., Soares-da-Silva P. Amino Acids 29:229-233(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[13]	"Identification of stereoselective transporters for S-nitroso-L-cysteine: role of LAT1 and LAT2 in biological activity of S-nitrosothiols." Li S., Whorton A.R. J. Biol. Chem. 280:20102-20110(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, INHIBITION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF135828 mRNA. Translation: AAF05695.1. AF135829 mRNA. Translation: AAF05696.1. AF135830 mRNA. Translation: AAF05697.1. AF171669 mRNA. Translation: AAF20381.1. Y18483 mRNA. Translation: CAB40137.1. AB037669 mRNA. Translation: BAB21519.1. AK313465 mRNA. Translation: BAG36251.1. CH471078 Genomic DNA. Translation: EAW66181.1. CH471078 Genomic DNA. Translation: EAW66182.1. BC052250 mRNA. Translation: AAH52250.1.
IPI	IPI00296114.
RefSeq	NP_001253965.1. NM_001267036.1. NP_001253966.1. NM_001267037.1. NP_036376.2. NM_012244.3. NP_877392.1. NM_182728.2.
UniGene	Hs.596643.
3D structure databases
ProteinModelPortal	Q9UHI5.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000320378.
PTM databases
PhosphoSite	Q9UHI5.
Polymorphism databases
DMDM	12643348.
Proteomic databases
PaxDb	Q9UHI5.
PRIDE	Q9UHI5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000316902; ENSP00000320378; ENSG00000092068.
GeneID	23428.
KEGG	hsa:23428.
UCSC	uc001wix.3. human.
Organism-specific databases
CTD	23428.
GeneCards	GC14M023594.
HGNC	HGNC:11066. SLC7A8.
MIM	604235. gene.
neXtProt	NX_Q9UHI5.
PharmGKB	PA35926.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0531.
HOVERGEN	HBG000476.
InParanoid	Q9UHI5.
KO	K13781.
OMA	DERPAKE.
OrthoDB	EOG4V437M.
PhylomeDB	Q9UHI5.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000092068-MONOMER.
Reactome	REACT_15518. Transmembrane transport of small molecules. REACT_19419. Amino acid and oligopeptide SLC transporters. REACT_604. Hemostasis.
SABIO-RK	Q9UHI5.
Gene expression databases
ArrayExpress	Q9UHI5.
Bgee	Q9UHI5.
CleanEx	HS_LAT2. HS_SLC7A8.
Genevestigator	Q9UHI5.
GermOnline	ENSG00000092068. Homo sapiens.
Family and domain databases
InterPro	IPR002293. AA/rel_permease1. IPR004760. L_AA_transporter. [Graphical view]
PANTHER	PTHR11785. PTHR11785. 1 hit.
PIRSF	PIRSF006060. AA_transporter. 1 hit.
TIGRFAMs	TIGR00911. 2A0308. 1 hit.
ProtoNet	Search...
Other
BindingDB	Q9UHI5.
ChEMBL	CHEMBL4301.
DrugBank	DB00160. L-Alanine. DB00130. L-Glutamine. DB00120. L-Phenylalanine.
GenomeRNAi	23428.
NextBio	45663.
SOURCE	Search...

Entry information

Entry name

LAT2_HUMAN

Accession

Primary (citable) accession number: Q9UHI5
Secondary accession number(s): B2R8Q4 , D3DS46, Q9UKQ6, Q9UKQ7, Q9UKQ8, Q9Y445

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 118 of the entry and version 1 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.