LAT2_HUMAN
ID LAT2_HUMAN Reviewed; 535 AA.
AC Q9UHI5; B2R8Q4; B4DKT4; B4DTV6; D3DS46; F2Z2J4; Q86U05; Q9UKQ6; Q9UKQ7;
AC Q9UKQ8; Q9Y445;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Large neutral amino acids transporter small subunit 2;
DE AltName: Full=L-type amino acid transporter 2;
DE Short=hLAT2;
DE AltName: Full=Solute carrier family 7 member 8;
GN Name=SLC7A8; Synonyms=LAT2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INHIBITION.
RX PubMed=10391915; DOI=10.1074/jbc.274.28.19738;
RA Pineda M., Fernandez E., Torrents D., Estevez R., Lopez C., Camps M.,
RA Lloberas J., Zorzano A., Palacin M.;
RT "Identification of a membrane protein, LAT-2, that co-expresses with 4F2
RT heavy chain, an L-type amino acid transport activity with broad specificity
RT for small and large zwitterionic amino acids.";
RL J. Biol. Chem. 274:19738-19744(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBUNIT.
RC TISSUE=Melanocyte;
RX PubMed=10574970; DOI=10.1074/jbc.274.49.34948;
RA Rossier G., Meier C., Bauch C., Summa V., Sordat B., Verrey F., Kuehn L.C.;
RT "LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of
RT kidney and intestine.";
RL J. Biol. Chem. 274:34948-34954(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=10080183; DOI=10.1038/6815;
RA Borsani G., Bassi M.T., Sperandeo M.P., De Grandi A., Buoninconti A.,
RA Riboni M., Manzoni M., Incerti B., Pepe A., Andria G., Ballabio A.,
RA Sebastio G.;
RT "SLC7A7, encoding a putative permease-related protein, is mutated in
RT patients with lysinuric protein intolerance.";
RL Nat. Genet. 21:297-301(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INHIBITION.
RC TISSUE=Kidney;
RX PubMed=15918515; DOI=10.1007/bf02977671;
RA Park S.Y., Kim J.-K., Kim I.J., Choi B.K., Jung K.Y., Lee S., Park K.J.,
RA Chairoungdua A., Kanai Y., Endou H., Kim D.K.;
RT "Reabsorption of neutral amino acids mediated by amino acid transporter
RT LAT2 and TAT1 in the basolateral membrane of proximal tubule.";
RL Arch. Pharm. Res. 28:421-432(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
RC TISSUE=Hippocampus, Placenta, and Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP FUNCTION, AND SUBUNIT.
RX PubMed=11311135; DOI=10.1042/bj3550725;
RA Broeer A., Friedrich B., Wagner C.A., Fillon S., Ganapathy V., Lang F.,
RA Broeer S.;
RT "Association of 4F2hc with light chains LAT1, LAT2 or y+LAT2 requires
RT different domains.";
RL Biochem. J. 355:725-731(2001).
RN [11]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND INHIBITION.
RX PubMed=12117417; DOI=10.1042/bj20020841;
RA Simmons-Willis T.A., Koh A.S., Clarkson T.W., Ballatori N.;
RT "Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-
RT cysteine complex is a substrate for human L-type large neutral amino acid
RT transporter (LAT) 1 and LAT2.";
RL Biochem. J. 367:239-246(2002).
RN [12]
RP FUNCTION, SUBUNIT, AND INDUCTION.
RX PubMed=12716892; DOI=10.1074/jbc.m302777200;
RA Liu X., Charrier L., Gewirtz A., Sitaraman S., Merlin D.;
RT "CD98 and intracellular adhesion molecule I regulate the activity of amino
RT acid transporter LAT-2 in polarized intestinal epithelia.";
RL J. Biol. Chem. 278:23672-23677(2003).
RN [13]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, AND
RP INHIBITION.
RX PubMed=15081149; DOI=10.1016/j.ijpharm.2004.01.035;
RA Gandhi M.D., Pal D., Mitra A.K.;
RT "Identification and functional characterization of a Na(+)-independent
RT large neutral amino acid transporter (LAT2) on ARPE-19 cells.";
RL Int. J. Pharm. 275:189-200(2004).
RN [14]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16027961; DOI=10.1007/s00726-005-0221-x;
RA Fraga S., Pinho M.J., Soares-da-Silva P.;
RT "Expression of LAT1 and LAT2 amino acid transporters in human and rat
RT intestinal epithelial cells.";
RL Amino Acids 29:229-233(2005).
RN [15]
RP FUNCTION, SUBUNIT, AND INHIBITION.
RX PubMed=15769744; DOI=10.1074/jbc.m413164200;
RA Li S., Whorton A.R.;
RT "Identification of stereoselective transporters for S-nitroso-L-cysteine:
RT role of LAT1 and LAT2 in biological activity of S-nitrosothiols.";
RL J. Biol. Chem. 280:20102-20110(2005).
CC -!- FUNCTION: Sodium-independent, high-affinity transport of small and
CC large neutral amino acids such as alanine, serine, threonine, cysteine,
CC phenylalanine, tyrosine, leucine, arginine and tryptophan, when
CC associated with SLC3A2/4F2hc. Acts as an amino acid exchanger. Has
CC higher affinity for L-phenylalanine than LAT1 but lower affinity for
CC glutamine and serine. L-alanine is transported at physiological
CC concentrations. Plays a role in basolateral (re)absorption of neutral
CC amino acids. Involved in the uptake of methylmercury (MeHg) when
CC administered as the L-cysteine or D,L-homocysteine complexes, and hence
CC plays a role in metal ion homeostasis and toxicity. Involved in the
CC cellular activity of small molecular weight nitrosothiols, via the
CC stereoselective transport of L-nitrosocysteine (L-CNSO) across the
CC transmembrane. Plays an essential role in the reabsorption of neutral
CC amino acids from the epithelial cells to the bloodstream in the kidney.
CC {ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:10574970,
CC ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:12117417,
CC ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:15081149,
CC ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15918515}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=221 uM for L-leucine {ECO:0000269|PubMed:10391915,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:15081149,
CC ECO:0000269|PubMed:15918515};
CC KM=64 uM for MeHg-L-cysteine {ECO:0000269|PubMed:10391915,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:15081149,
CC ECO:0000269|PubMed:15918515};
CC KM=161 uM for methionine {ECO:0000269|PubMed:10391915,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:15081149,
CC ECO:0000269|PubMed:15918515};
CC KM=978 uM for L-alanine {ECO:0000269|PubMed:10391915,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:15081149,
CC ECO:0000269|PubMed:15918515};
CC KM=89.35 uM for L-phenylalanine {ECO:0000269|PubMed:10391915,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:15081149,
CC ECO:0000269|PubMed:15918515};
CC KM=57.3 uM for L-tryptophan {ECO:0000269|PubMed:10391915,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:15081149,
CC ECO:0000269|PubMed:15918515};
CC KM=48.8 uM for L-tyrosine {ECO:0000269|PubMed:10391915,
CC ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:15081149,
CC ECO:0000269|PubMed:15918515};
CC -!- SUBUNIT: Disulfide-linked heterodimer with the amino acid transport
CC protein SLC3A2/4F2hc. {ECO:0000269|PubMed:10391915,
CC ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:11311135,
CC ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:15769744,
CC ECO:0000269|PubMed:15918515}.
CC -!- INTERACTION:
CC Q9UHI5; O95870: ABHD16A; NbExp=3; IntAct=EBI-13292283, EBI-348517;
CC Q9UHI5; Q9NRZ5: AGPAT4; NbExp=3; IntAct=EBI-13292283, EBI-1754287;
CC Q9UHI5; Q13520: AQP6; NbExp=3; IntAct=EBI-13292283, EBI-13059134;
CC Q9UHI5; P21964: COMT; NbExp=3; IntAct=EBI-13292283, EBI-372265;
CC Q9UHI5; Q9BUN8: DERL1; NbExp=3; IntAct=EBI-13292283, EBI-398977;
CC Q9UHI5; O75460-2: ERN1; NbExp=3; IntAct=EBI-13292283, EBI-25852368;
CC Q9UHI5; P22607: FGFR3; NbExp=3; IntAct=EBI-13292283, EBI-348399;
CC Q9UHI5; Q0VDC6: FKBP1A; NbExp=3; IntAct=EBI-13292283, EBI-10226858;
CC Q9UHI5; P06396: GSN; NbExp=3; IntAct=EBI-13292283, EBI-351506;
CC Q9UHI5; P54652: HSPA2; NbExp=3; IntAct=EBI-13292283, EBI-356991;
CC Q9UHI5; P11021: HSPA5; NbExp=3; IntAct=EBI-13292283, EBI-354921;
CC Q9UHI5; Q9GZY8-5: MFF; NbExp=3; IntAct=EBI-13292283, EBI-11956541;
CC Q9UHI5; Q96ES6: MFSD3; NbExp=3; IntAct=EBI-13292283, EBI-745345;
CC Q9UHI5; O95167: NDUFA3; NbExp=3; IntAct=EBI-13292283, EBI-1246131;
CC Q9UHI5; Q9NZG7: NINJ2; NbExp=3; IntAct=EBI-13292283, EBI-10317425;
CC Q9UHI5; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-13292283, EBI-7545592;
CC Q9UHI5; O15389: SIGLEC5; NbExp=3; IntAct=EBI-13292283, EBI-750381;
CC Q9UHI5; Q96AG3: SLC25A46; NbExp=3; IntAct=EBI-13292283, EBI-10281975;
CC Q9UHI5; Q9BRI3: SLC30A2; NbExp=3; IntAct=EBI-13292283, EBI-8644112;
CC Q9UHI5; P08195-4: SLC3A2; NbExp=3; IntAct=EBI-13292283, EBI-12832276;
CC Q9UHI5; O60906: SMPD2; NbExp=3; IntAct=EBI-13292283, EBI-12828299;
CC Q9UHI5; Q6UX34: SNORC; NbExp=3; IntAct=EBI-13292283, EBI-11957067;
CC Q9UHI5; P57105: SYNJ2BP; NbExp=3; IntAct=EBI-13292283, EBI-1049004;
CC Q9UHI5; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-13292283, EBI-8638294;
CC Q9UHI5; Q9BTX3: TMEM208; NbExp=3; IntAct=EBI-13292283, EBI-12876824;
CC Q9UHI5; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-13292283, EBI-2852148;
CC Q9UHI5; Q6PI78: TMEM65; NbExp=3; IntAct=EBI-13292283, EBI-6656213;
CC Q9UHI5; Q9Y548: YIPF1; NbExp=3; IntAct=EBI-13292283, EBI-7850136;
CC Q9UHI5; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-13292283, EBI-751210;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Basolateral cell membrane; Multi-pass
CC membrane protein. Note=Localized to the cytoplasm when expressed alone
CC but when coexpressed with SLC3A2/4F2hc, is localized to the plasma
CC membrane. Colocalized with SLC3A2/4F2hc at the basolateral membrane of
CC kidney cortex proximal tubules and small intestine epithelia of the
CC villi.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9UHI5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UHI5-2; Sequence=VSP_046946;
CC Name=3;
CC IsoId=Q9UHI5-3; Sequence=VSP_046945;
CC Name=4;
CC IsoId=Q9UHI5-4; Sequence=VSP_046947;
CC -!- TISSUE SPECIFICITY: Strongest expression is observed in kidney and
CC moderate expression in placenta and brain, followed by liver, prostate,
CC testis, ovary, lymph node, thymus, spleen, skeletal muscle and heart.
CC Also expressed in fetal liver as well as in the retinal pigment
CC epithelial cell line ARPE-19 and the intestinal epithelial cell line
CC Caco-2. {ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:15081149,
CC ECO:0000269|PubMed:15918515, ECO:0000269|PubMed:16027961}.
CC -!- INDUCTION: Activity in polarized intestinal cells is regulated by the
CC association between SLC3A2/4F2 (in the SLC3A2/4F2-LAT2 heterodimer) and
CC ICAM1. {ECO:0000269|PubMed:12716892}.
CC -!- MISCELLANEOUS: L-leucine transport activity inhibited by small
CC zwitterionic amino acids (i.e. glycine, alanine, serine, threonine
CC asparagine, glutamine, methionine, leucine, isoleucine, valine,
CC phenylalanine, tyrosine, tryptophan, histidine and cysteine) and by
CC glutamine and asparagine. Methionine uptake was inhibited by the L-
CC system substrates L-leucine, 2-amino-bicyclo-(2,2,1)-heptane-2-
CC carboxylate (BCH), L-cysteine and by the MeHg-L-cysteine complex and
CC structurally related S-ethyl-L-cysteine. MeHg-L-cysteine uptake is
CC inhibited by L-methionine, L-leucine, BCH and S-ethyl-L-cysteine. L-
CC leucine uptake was inhibited by L-CNSO.
CC -!- SIMILARITY: Belongs to the amino acid-polyamine-organocation (APC)
CC superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD62616.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF135828; AAF05695.1; -; mRNA.
DR EMBL; AF135829; AAF05696.1; -; mRNA.
DR EMBL; AF135830; AAF05697.1; -; mRNA.
DR EMBL; AF171669; AAF20381.1; -; mRNA.
DR EMBL; Y18483; CAB40137.1; -; mRNA.
DR EMBL; AB037669; BAB21519.1; -; mRNA.
DR EMBL; BX248288; CAD62616.1; ALT_INIT; mRNA.
DR EMBL; AK296702; BAG59296.1; -; mRNA.
DR EMBL; AK300384; BAG62118.1; -; mRNA.
DR EMBL; AK313465; BAG36251.1; -; mRNA.
DR EMBL; AL117258; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW66181.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW66182.1; -; Genomic_DNA.
DR EMBL; BC052250; AAH52250.1; -; mRNA.
DR CCDS; CCDS41924.1; -. [Q9UHI5-2]
DR CCDS; CCDS58304.1; -. [Q9UHI5-3]
DR CCDS; CCDS58305.1; -. [Q9UHI5-4]
DR CCDS; CCDS9590.1; -. [Q9UHI5-1]
DR RefSeq; NP_001253965.1; NM_001267036.1. [Q9UHI5-4]
DR RefSeq; NP_001253966.1; NM_001267037.1. [Q9UHI5-3]
DR RefSeq; NP_036376.2; NM_012244.3. [Q9UHI5-1]
DR RefSeq; NP_877392.1; NM_182728.2. [Q9UHI5-2]
DR PDB; 7B00; EM; 3.98 A; A=1-535.
DR PDB; 7CMH; EM; 3.40 A; B=2-535.
DR PDB; 7CMI; EM; 2.90 A; B=2-535.
DR PDBsum; 7B00; -.
DR PDBsum; 7CMH; -.
DR PDBsum; 7CMI; -.
DR AlphaFoldDB; Q9UHI5; -.
DR SMR; Q9UHI5; -.
DR BioGRID; 116996; 31.
DR CORUM; Q9UHI5; -.
DR IntAct; Q9UHI5; 29.
DR STRING; 9606.ENSP00000320378; -.
DR BindingDB; Q9UHI5; -.
DR ChEMBL; CHEMBL4301; -.
DR DrugBank; DB00160; Alanine.
DR DrugBank; DB00130; L-Glutamine.
DR DrugBank; DB01235; Levodopa.
DR DrugBank; DB00120; Phenylalanine.
DR DrugBank; DB02750; S-(Methylmercury)-L-Cysteine.
DR TCDB; 2.A.3.8.20; the amino acid-polyamine-organocation (apc) family.
DR iPTMnet; Q9UHI5; -.
DR PhosphoSitePlus; Q9UHI5; -.
DR SwissPalm; Q9UHI5; -.
DR BioMuta; SLC7A8; -.
DR DMDM; 12643348; -.
DR EPD; Q9UHI5; -.
DR jPOST; Q9UHI5; -.
DR MassIVE; Q9UHI5; -.
DR PaxDb; Q9UHI5; -.
DR PeptideAtlas; Q9UHI5; -.
DR PRIDE; Q9UHI5; -.
DR ProteomicsDB; 23734; -.
DR ProteomicsDB; 4485; -.
DR ProteomicsDB; 5131; -.
DR ProteomicsDB; 84356; -. [Q9UHI5-1]
DR Antibodypedia; 22403; 241 antibodies from 24 providers.
DR DNASU; 23428; -.
DR Ensembl; ENST00000316902.12; ENSP00000320378.7; ENSG00000092068.21. [Q9UHI5-1]
DR Ensembl; ENST00000422941.6; ENSP00000416398.2; ENSG00000092068.21. [Q9UHI5-3]
DR Ensembl; ENST00000453702.5; ENSP00000391577.1; ENSG00000092068.21. [Q9UHI5-2]
DR Ensembl; ENST00000529705.6; ENSP00000434345.2; ENSG00000092068.21. [Q9UHI5-4]
DR GeneID; 23428; -.
DR KEGG; hsa:23428; -.
DR MANE-Select; ENST00000316902.12; ENSP00000320378.7; NM_012244.4; NP_036376.2.
DR UCSC; uc001wix.5; human. [Q9UHI5-1]
DR CTD; 23428; -.
DR DisGeNET; 23428; -.
DR GeneCards; SLC7A8; -.
DR HGNC; HGNC:11066; SLC7A8.
DR HPA; ENSG00000092068; Tissue enhanced (parathyroid).
DR MIM; 604235; gene.
DR neXtProt; NX_Q9UHI5; -.
DR OpenTargets; ENSG00000092068; -.
DR PharmGKB; PA35926; -.
DR VEuPathDB; HostDB:ENSG00000092068; -.
DR eggNOG; KOG1287; Eukaryota.
DR GeneTree; ENSGT00940000158278; -.
DR HOGENOM; CLU_007946_3_0_1; -.
DR InParanoid; Q9UHI5; -.
DR OMA; FTHLWND; -.
DR PhylomeDB; Q9UHI5; -.
DR TreeFam; TF313355; -.
DR BioCyc; MetaCyc:ENSG00000092068-MON; -.
DR PathwayCommons; Q9UHI5; -.
DR Reactome; R-HSA-210991; Basigin interactions.
DR Reactome; R-HSA-352230; Amino acid transport across the plasma membrane.
DR SABIO-RK; Q9UHI5; -.
DR SignaLink; Q9UHI5; -.
DR BioGRID-ORCS; 23428; 164 hits in 1082 CRISPR screens.
DR ChiTaRS; SLC7A8; human.
DR GeneWiki; SLC7A8; -.
DR GenomeRNAi; 23428; -.
DR Pharos; Q9UHI5; Tbio.
DR PRO; PR:Q9UHI5; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9UHI5; protein.
DR Bgee; ENSG00000092068; Expressed in islet of Langerhans and 202 other tissues.
DR ExpressionAtlas; Q9UHI5; baseline and differential.
DR Genevisible; Q9UHI5; HS.
DR GO; GO:0016324; C:apical plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0009925; C:basal plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0031528; C:microvillus membrane; IDA:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0015171; F:amino acid transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015187; F:glycine transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0015180; F:L-alanine transmembrane transporter activity; IGI:ARUK-UCL.
DR GO; GO:0015179; F:L-amino acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015190; F:L-leucine transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0015175; F:neutral amino acid transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0015101; F:organic cation transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0042605; F:peptide antigen binding; ISS:UniProtKB.
DR GO; GO:0015349; F:thyroid hormone transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0019534; F:toxin transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0089718; P:amino acid import across plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0006865; P:amino acid transport; IDA:UniProtKB.
DR GO; GO:0015816; P:glycine transport; ISS:ARUK-UCL.
DR GO; GO:1904273; P:L-alanine import across plasma membrane; IGI:ARUK-UCL.
DR GO; GO:1903801; P:L-leucine import across plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0098713; P:leucine import across plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0015820; P:leucine transport; ISS:ARUK-UCL.
DR GO; GO:0055065; P:metal ion homeostasis; NAS:UniProtKB.
DR GO; GO:0015804; P:neutral amino acid transport; ISS:UniProtKB.
DR GO; GO:0035524; P:proline transmembrane transport; ISS:ARUK-UCL.
DR GO; GO:0009636; P:response to toxic substance; NAS:UniProtKB.
DR GO; GO:0070327; P:thyroid hormone transport; IDA:ARUK-UCL.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR GO; GO:0015827; P:tryptophan transport; ISS:ARUK-UCL.
DR GO; GO:0015829; P:valine transport; ISS:ARUK-UCL.
DR InterPro; IPR002293; AA/rel_permease1.
DR InterPro; IPR004760; L_AA_transporter.
DR Pfam; PF13520; AA_permease_2; 1.
DR TIGRFAMs; TIGR00911; 2A0308; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Amino-acid transport; Cell membrane;
KW Cytoplasm; Disulfide bond; Membrane; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..535
FT /note="Large neutral amino acids transporter small subunit
FT 2"
FT /id="PRO_0000054273"
FT TRANSMEM 40..60
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 72..92
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 113..133
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 155..175
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 189..209
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 231..251
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 268..288
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 310..330
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 362..382
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 388..408
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 424..444
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 447..467
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 502..535
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..20
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 513..535
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXW9"
FT VAR_SEQ 1..263
FT /note="MEEGARHRNNTEKKHPGGGESDASPEAGSGGGGVALKKEIGLVSACGIIVGN
FT IIGSGIFVSPKGVLENAGSVGLALIVWIVTGFITVVGALCYAELGVTIPKSGGDYSYVK
FT DIFGGLAGFLRLWIAVLVIYPTNQAVIALTFSNYVLQPLFPTCFPPESGLRLLAAICLL
FT LLTWVNCSSVRWATRVQDIFTAGKLLALALIIIMGIVQICKGEYFWLEPKNAFENFQEP
FT DIGLVALAFLQGSFAYGGWNFLNYVTEELVDPYK -> MGQLFQCAVGHPGSRHLHSWE
FT APGLGPDYHHGDCTDMQR (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046945"
FT VAR_SEQ 1..203
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_046946"
FT VAR_SEQ 1..169
FT /note="MEEGARHRNNTEKKHPGGGESDASPEAGSGGGGVALKKEIGLVSACGIIVGN
FT IIGSGIFVSPKGVLENAGSVGLALIVWIVTGFITVVGALCYAELGVTIPKSGGDYSYVK
FT DIFGGLAGFLRLWIAVLVIYPTNQAVIALTFSNYVLQPLFPTCFPPESGLRLLAAICL
FT -> MGQYGQELSWKCLVKAVCLQEHSQPSQLLCTLLLCWCVLGRERPFRKAQSTSSPLE
FT GVPRFLKR (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046947"
FT CONFLICT 225
FT /note="N -> D (in Ref. 3; CAB40137)"
FT /evidence="ECO:0000305"
FT CONFLICT 401
FT /note="V -> G (in Ref. 3; CAB40137)"
FT /evidence="ECO:0000305"
FT CONFLICT 503
FT /note="G -> R (in Ref. 1; AAF05696/AAF05697)"
FT /evidence="ECO:0000305"
FT HELIX 42..53
FT /evidence="ECO:0007829|PDB:7CMI"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:7CMI"
FT TURN 58..61
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 62..69
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 72..99
FT /evidence="ECO:0007829|PDB:7CMI"
FT TURN 103..105
FT /evidence="ECO:0007829|PDB:7CMH"
FT HELIX 106..112
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 117..128
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 130..146
FT /evidence="ECO:0007829|PDB:7CMI"
FT STRAND 147..154
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 158..177
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 180..185
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 189..209
FT /evidence="ECO:0007829|PDB:7CMI"
FT TURN 210..212
FT /evidence="ECO:0007829|PDB:7CMI"
FT STRAND 215..217
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 231..233
FT /evidence="ECO:0007829|PDB:7CMH"
FT HELIX 234..241
FT /evidence="ECO:0007829|PDB:7CMI"
FT TURN 242..245
FT /evidence="ECO:0007829|PDB:7CMI"
FT TURN 249..254
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:7CMI"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:7CMI"
FT STRAND 262..265
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 266..288
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 293..296
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 302..308
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 314..335
FT /evidence="ECO:0007829|PDB:7CMI"
FT TURN 336..338
FT /evidence="ECO:0007829|PDB:7CMH"
FT HELIX 339..345
FT /evidence="ECO:0007829|PDB:7CMI"
FT TURN 346..348
FT /evidence="ECO:0007829|PDB:7CMI"
FT STRAND 357..361
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 365..377
FT /evidence="ECO:0007829|PDB:7CMI"
FT STRAND 380..382
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 386..411
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 426..444
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 446..466
FT /evidence="ECO:0007829|PDB:7CMI"
FT HELIX 474..490
FT /evidence="ECO:0007829|PDB:7CMI"
SQ SEQUENCE 535 AA; 58382 MW; AC129146353F1E47 CRC64;
MEEGARHRNN TEKKHPGGGE SDASPEAGSG GGGVALKKEI GLVSACGIIV GNIIGSGIFV
SPKGVLENAG SVGLALIVWI VTGFITVVGA LCYAELGVTI PKSGGDYSYV KDIFGGLAGF
LRLWIAVLVI YPTNQAVIAL TFSNYVLQPL FPTCFPPESG LRLLAAICLL LLTWVNCSSV
RWATRVQDIF TAGKLLALAL IIIMGIVQIC KGEYFWLEPK NAFENFQEPD IGLVALAFLQ
GSFAYGGWNF LNYVTEELVD PYKNLPRAIF ISIPLVTFVY VFANVAYVTA MSPQELLASN
AVAVTFGEKL LGVMAWIMPI SVALSTFGGV NGSLFTSSRL FFAGAREGHL PSVLAMIHVK
RCTPIPALLF TCISTLLMLV TSDMYTLINY VGFINYLFYG VTVAGQIVLR WKKPDIPRPI
KINLLFPIIY LLFWAFLLVF SLWSEPVVCG IGLAIMLTGV PVYFLGVYWQ HKPKCFSDFI
ELLTLVSQKM CVVVYPEVER GSGTEEANED MEEQQQPMYQ PTPTKDKDVA GQPQP
