EAA1_HUMAN
ID EAA1_HUMAN Reviewed; 542 AA.
AC P43003; B2R5T3; Q4JCQ8;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Excitatory amino acid transporter 1 {ECO:0000303|PubMed:16042756, ECO:0000303|PubMed:8647279};
DE AltName: Full=Sodium-dependent glutamate/aspartate transporter 1 {ECO:0000303|PubMed:8647279};
DE Short=GLAST-1 {ECO:0000303|PubMed:8647279};
DE AltName: Full=Solute carrier family 1 member 3;
GN Name=SLC1A3 {ECO:0000312|HGNC:HGNC:10941};
GN Synonyms=EAAT1 {ECO:0000303|PubMed:16042756, ECO:0000303|PubMed:8647279},
GN GLAST, GLAST1 {ECO:0000303|PubMed:8647279};
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), AND TISSUE SPECIFICITY.
RC TISSUE=Cerebellum;
RX PubMed=8218410; DOI=10.1016/0167-4781(93)90057-k;
RA Shashidharan P., Plaitakis A.;
RT "Cloning and characterization of a glutamate transporter cDNA from human
RT cerebellum.";
RL Biochim. Biophys. Acta 1216:161-164(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Brain cortex;
RX PubMed=7521911; DOI=10.1523/jneurosci.14-09-05559.1994;
RA Arriza J.L., Fairman W.A., Wendy A., Wadiche J.I., Murdoch G.H.,
RA Kavanaugh M.P., Amara S.G.;
RT "Functional comparisons of three glutamate transporter subtypes cloned from
RT human motor cortex.";
RL J. Neurosci. 14:5559-5569(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=8123008; DOI=10.1006/bbrc.1994.1210;
RA Kawakami H., Tanaka K., Nakayama T., Inoue K., Nakamura S.;
RT "Cloning and expression of a human glutamate transporter.";
RL Biochem. Biophys. Res. Commun. 199:171-176(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8647279; DOI=10.1016/0014-5793(96)00424-3;
RA Stoffel W., Sasse J., Dueker M., Mueller R., Hofmann K.O., Fink T.,
RA Lichter P.;
RT "Human high affinity, Na(+)-dependent L-glutamate/L-aspartate transporter
RT GLAST-1 (EAAT-1): gene structure and localization to chromosome 5p11-p12.";
RL FEBS Lett. 386:189-193(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=16042756; DOI=10.1111/j.1471-4159.2005.03370.x;
RA Vallejo-Illarramendi A., Domercq M., Matute C.;
RT "A novel alternative splicing form of excitatory amino acid transporter 1
RT is a negative regulator of glutamate uptake.";
RL J. Neurochem. 95:341-348(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cerebellum;
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=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-363 AND ARG-477.
RX PubMed=20477940; DOI=10.1111/j.1471-4159.2010.06796.x;
RA Ryan R.M., Kortt N.C., Sirivanta T., Vandenberg R.J.;
RT "The position of an arginine residue influences substrate affinity and K+
RT coupling in the human glutamate transporter, EAAT1.";
RL J. Neurochem. 114:565-575(2010).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-512, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP TRANSPORTER ACTIVITY.
RX PubMed=26690923; DOI=10.1007/s00232-015-9863-0;
RA Abousaab A., Warsi J., Elvira B., Lang F.;
RT "Caveolin-1 Sensitivity of Excitatory Amino Acid Transporters EAAT1, EAAT2,
RT EAAT3, and EAAT4.";
RL J. Membr. Biol. 249:239-249(2016).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-523.
RX PubMed=28032905; DOI=10.1002/1873-3468.12549;
RA Krycer J.R., Fazakerley D.J., Cater R.J., C Thomas K., Naghiloo S.,
RA Burchfield J.G., Humphrey S.J., Vandenberg R.J., Ryan R.M., James D.E.;
RT "The amino acid transporter, SLC1A3, is plasma membrane-localised in
RT adipocytes and its activity is insensitive to insulin.";
RL FEBS Lett. 591:322-330(2017).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 1-148 AND 243-542 IN COMPLEXES
RP WITH SODIUM; ASPARTATE AND ALLOSTERIC INHIBITOR, FUNCTION, TOPOLOGY,
RP SUBUNIT, AND DOMAIN.
RX PubMed=28424515; DOI=10.1038/nature22064;
RA Canul-Tec J.C., Assal R., Cirri E., Legrand P., Brier S., Chamot-Rooke J.,
RA Reyes N.;
RT "Structure and allosteric inhibition of excitatory amino acid transporter
RT 1.";
RL Nature 544:446-451(2017).
RN [16]
RP VARIANT EA6 ARG-290.
RX PubMed=16116111; DOI=10.1212/01.wnl.0000172638.58172.5a;
RA Jen J.C., Wan J., Palos T.P., Howard B.D., Baloh R.W.;
RT "Mutation in the glutamate transporter EAAT1 causes episodic ataxia,
RT hemiplegia, and seizures.";
RL Neurology 65:529-534(2005).
CC -!- FUNCTION: Sodium-dependent, high-affinity amino acid transporter that
CC mediates the uptake of L-glutamate and also L-aspartate and D-aspartate
CC (PubMed:7521911, PubMed:8123008, PubMed:20477940, PubMed:26690923,
CC PubMed:28032905, PubMed:28424515). Functions as a symporter that
CC transports one amino acid molecule together with two or three Na(+)
CC ions and one proton, in parallel with the counter-transport of one K(+)
CC ion (PubMed:20477940). Mediates Cl(-) flux that is not coupled to amino
CC acid transport; this avoids the accumulation of negative charges due to
CC aspartate and Na(+) symport (PubMed:20477940). Plays a redundant role
CC in the rapid removal of released glutamate from the synaptic cleft,
CC which is essential for terminating the postsynaptic action of glutamate
CC (By similarity). {ECO:0000250|UniProtKB:P56564,
CC ECO:0000269|PubMed:20477940, ECO:0000269|PubMed:26690923,
CC ECO:0000269|PubMed:28032905, ECO:0000269|PubMed:28424515,
CC ECO:0000269|PubMed:7521911, ECO:0000269|PubMed:8123008}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(out) + K(+)(in) + L-glutamate(out) + 3 Na(+)(out) =
CC H(+)(in) + K(+)(out) + L-glutamate(in) + 3 Na(+)(in);
CC Xref=Rhea:RHEA:70699, ChEBI:CHEBI:15378, ChEBI:CHEBI:29101,
CC ChEBI:CHEBI:29103, ChEBI:CHEBI:29985;
CC Evidence={ECO:0000269|PubMed:7521911};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(out) + K(+)(in) + L-aspartate(out) + 3 Na(+)(out) =
CC H(+)(in) + K(+)(out) + L-aspartate(in) + 3 Na(+)(in);
CC Xref=Rhea:RHEA:70851, ChEBI:CHEBI:15378, ChEBI:CHEBI:29101,
CC ChEBI:CHEBI:29103, ChEBI:CHEBI:29991;
CC Evidence={ECO:0000269|PubMed:7521911};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-aspartate(out) + H(+)(out) + K(+)(in) + 3 Na(+)(out) = D-
CC aspartate(in) + H(+)(in) + K(+)(out) + 3 Na(+)(in);
CC Xref=Rhea:RHEA:71379, ChEBI:CHEBI:15378, ChEBI:CHEBI:29101,
CC ChEBI:CHEBI:29103, ChEBI:CHEBI:29990;
CC Evidence={ECO:0000269|PubMed:7521911};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=62 uM for L-glutamate {ECO:0000269|PubMed:7521911};
CC KM=47 uM for D-aspartate {ECO:0000269|PubMed:7521911};
CC KM=20 uM for L-glutamate (when transfected in Xenopus laevis oocytes)
CC {ECO:0000269|PubMed:7521911};
CC KM=23 uM for D-aspartate (when transfected in Xenopus laevis oocytes)
CC {ECO:0000269|PubMed:7521911};
CC KM=16 uM for L-aspartate (when transfected in Xenopus laevis oocytes)
CC {ECO:0000269|PubMed:7521911};
CC KM=525 uM for L-glutamate (when transfected in Xenopus laevis
CC oocytes) {ECO:0000269|PubMed:26690923};
CC -!- SUBUNIT: Homotrimer (PubMed:28424515). {ECO:0000269|PubMed:28424515}.
CC -!- INTERACTION:
CC P43003; Q8WVV5: BTN2A2; NbExp=3; IntAct=EBI-359038, EBI-8648738;
CC P43003; O14880: MGST3; NbExp=3; IntAct=EBI-359038, EBI-724754;
CC P43003; A0PK00: TMEM120B; NbExp=3; IntAct=EBI-359038, EBI-10171534;
CC P43003; Q5BJH2-2: TMEM128; NbExp=3; IntAct=EBI-359038, EBI-10694905;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20477940,
CC ECO:0000269|PubMed:26690923, ECO:0000269|PubMed:28032905,
CC ECO:0000269|PubMed:7521911, ECO:0000269|PubMed:8123008}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:28424515}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P43003-1; Sequence=Displayed;
CC Name=2; Synonyms=EAAT1ex9skip;
CC IsoId=P43003-2; Sequence=VSP_043913;
CC -!- TISSUE SPECIFICITY: Detected in brain (PubMed:8218410, PubMed:7521911,
CC PubMed:8123008). Detected at very much lower levels in heart, lung,
CC placenta and skeletal muscle (PubMed:7521911, PubMed:8123008). Highly
CC expressed in cerebellum, but also found in frontal cortex, hippocampus
CC and basal ganglia (PubMed:7521911). {ECO:0000269|PubMed:7521911,
CC ECO:0000269|PubMed:8123008, ECO:0000269|PubMed:8218410}.
CC -!- DOMAIN: Contains eight transmembrane regions plus two helical hairpins
CC that dip into the membrane. These helical hairpin structures play an
CC important role in the transport process. The first enters the membrane
CC from the cytoplasmic side, the second one from the extracellular side.
CC During the transport cycle, the regions involved in amino acid
CC transport, and especially the helical hairpins, move vertically by
CC about 15-18 Angstroms, alternating between exposure to the aqueous
CC phase and reinsertion in the lipid bilayer. In contrast, the regions
CC involved in trimerization do not move. {ECO:0000305|PubMed:28424515}.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P24942}.
CC -!- DISEASE: Episodic ataxia 6 (EA6) [MIM:612656]: A disorder characterized
CC by episodic ataxia, seizures, migraine and alternating hemiplegia.
CC {ECO:0000269|PubMed:16116111}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Expressed throughout the CNS, both in gray
CC matter and axonal tracts, at levels ranging between 10% and 20% of
CC isoform 1. Localizes to ER, has no functional glutamate uptake
CC activity, and exerts a dominant negative effect isoform 1.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the dicarboxylate/amino acid:cation symporter
CC (DAACS) (TC 2.A.23) family. SLC1A3 subfamily. {ECO:0000305}.
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DR EMBL; L19158; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; U03504; AAA50428.1; -; mRNA.
DR EMBL; D26443; BAA05462.1; -; mRNA.
DR EMBL; Z31713; CAA83507.1; -; Genomic_DNA.
DR EMBL; Z31703; CAA83507.1; JOINED; Genomic_DNA.
DR EMBL; Z31704; CAA83507.1; JOINED; Genomic_DNA.
DR EMBL; Z31705; CAA83507.1; JOINED; Genomic_DNA.
DR EMBL; Z31706; CAA83507.1; JOINED; Genomic_DNA.
DR EMBL; Z31707; CAA83507.1; JOINED; Genomic_DNA.
DR EMBL; Z31708; CAA83507.1; JOINED; Genomic_DNA.
DR EMBL; Z31709; CAA83507.1; JOINED; Genomic_DNA.
DR EMBL; Z31710; CAA83507.1; JOINED; Genomic_DNA.
DR EMBL; AY954110; AAY28724.1; -; mRNA.
DR EMBL; AK312304; BAG35230.1; -; mRNA.
DR EMBL; AC008957; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010631; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471119; EAW55945.1; -; Genomic_DNA.
DR CCDS; CCDS3919.1; -. [P43003-1]
DR CCDS; CCDS54844.1; -. [P43003-2]
DR PIR; S38353; S38353.
DR RefSeq; NP_001160167.1; NM_001166695.2. [P43003-2]
DR RefSeq; NP_001276869.1; NM_001289940.1.
DR RefSeq; NP_004163.3; NM_004172.4. [P43003-1]
DR RefSeq; XP_005248399.1; XM_005248342.2. [P43003-1]
DR PDB; 5LLM; X-ray; 3.25 A; A=1-148, A=243-542.
DR PDB; 5LLU; X-ray; 3.32 A; A=1-148, A=243-542.
DR PDB; 5LM4; X-ray; 3.10 A; A=1-148, A=243-542.
DR PDB; 5MJU; X-ray; 3.71 A; A=1-148, A=243-542.
DR PDB; 7NPW; EM; 3.99 A; A/B/C=29-497.
DR PDBsum; 5LLM; -.
DR PDBsum; 5LLU; -.
DR PDBsum; 5LM4; -.
DR PDBsum; 5MJU; -.
DR PDBsum; 7NPW; -.
DR AlphaFoldDB; P43003; -.
DR SMR; P43003; -.
DR BioGRID; 112398; 92.
DR IntAct; P43003; 17.
DR MINT; P43003; -.
DR STRING; 9606.ENSP00000265113; -.
DR BindingDB; P43003; -.
DR ChEMBL; CHEMBL3085; -.
DR DrugBank; DB08868; Fingolimod.
DR DrugBank; DB00142; Glutamic acid.
DR DrugCentral; P43003; -.
DR GuidetoPHARMACOLOGY; 868; -.
DR TCDB; 2.A.23.2.6; the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.
DR iPTMnet; P43003; -.
DR PhosphoSitePlus; P43003; -.
DR SwissPalm; P43003; -.
DR BioMuta; SLC1A3; -.
DR DMDM; 1169458; -.
DR EPD; P43003; -.
DR jPOST; P43003; -.
DR MassIVE; P43003; -.
DR MaxQB; P43003; -.
DR PaxDb; P43003; -.
DR PeptideAtlas; P43003; -.
DR PRIDE; P43003; -.
DR ProteomicsDB; 55567; -. [P43003-1]
DR ProteomicsDB; 55568; -. [P43003-2]
DR Antibodypedia; 22936; 409 antibodies from 39 providers.
DR DNASU; 6507; -.
DR Ensembl; ENST00000265113.9; ENSP00000265113.4; ENSG00000079215.15. [P43003-1]
DR Ensembl; ENST00000381918.4; ENSP00000371343.4; ENSG00000079215.15. [P43003-1]
DR Ensembl; ENST00000679983.1; ENSP00000505238.1; ENSG00000079215.15. [P43003-1]
DR Ensembl; ENST00000679992.1; ENSP00000506585.1; ENSG00000079215.15. [P43003-1]
DR Ensembl; ENST00000680125.1; ENSP00000506424.1; ENSG00000079215.15. [P43003-2]
DR Ensembl; ENST00000680318.1; ENSP00000505057.1; ENSG00000079215.15. [P43003-1]
DR Ensembl; ENST00000681926.1; ENSP00000505850.1; ENSG00000079215.15. [P43003-2]
DR GeneID; 6507; -.
DR KEGG; hsa:6507; -.
DR MANE-Select; ENST00000265113.9; ENSP00000265113.4; NM_004172.5; NP_004163.3.
DR UCSC; uc003jkj.4; human. [P43003-1]
DR CTD; 6507; -.
DR DisGeNET; 6507; -.
DR GeneCards; SLC1A3; -.
DR HGNC; HGNC:10941; SLC1A3.
DR HPA; ENSG00000079215; Group enriched (brain, choroid plexus, retina).
DR MalaCards; SLC1A3; -.
DR MIM; 600111; gene.
DR MIM; 612656; phenotype.
DR neXtProt; NX_P43003; -.
DR OpenTargets; ENSG00000079215; -.
DR Orphanet; 2131; Alternating hemiplegia of childhood.
DR Orphanet; 209967; Episodic ataxia type 6.
DR PharmGKB; PA35828; -.
DR VEuPathDB; HostDB:ENSG00000079215; -.
DR eggNOG; KOG3787; Eukaryota.
DR GeneTree; ENSGT00940000155464; -.
DR InParanoid; P43003; -.
DR OMA; GHGMNVD; -.
DR OrthoDB; 540689at2759; -.
DR PhylomeDB; P43003; -.
DR TreeFam; TF315206; -.
DR PathwayCommons; P43003; -.
DR Reactome; R-HSA-210455; Astrocytic Glutamate-Glutamine Uptake And Metabolism.
DR Reactome; R-HSA-210500; Glutamate Neurotransmitter Release Cycle.
DR Reactome; R-HSA-425393; Transport of inorganic cations/anions and amino acids/oligopeptides.
DR Reactome; R-HSA-5619062; Defective SLC1A3 causes episodic ataxia 6 (EA6).
DR SignaLink; P43003; -.
DR SIGNOR; P43003; -.
DR BioGRID-ORCS; 6507; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; SLC1A3; human.
DR GeneWiki; Glutamate_aspartate_transporter; -.
DR GenomeRNAi; 6507; -.
DR Pharos; P43003; Tchem.
DR PRO; PR:P43003; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P43003; protein.
DR Bgee; ENSG00000079215; Expressed in ventricular zone and 193 other tissues.
DR ExpressionAtlas; P43003; baseline and differential.
DR Genevisible; P43003; HS.
DR GO; GO:0009925; C:basal plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:ARUK-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0098796; C:membrane protein complex; ISS:ARUK-UCL.
DR GO; GO:0043005; C:neuron projection; ISS:ARUK-UCL.
DR GO; GO:0043025; C:neuronal cell body; ISS:ARUK-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0016595; F:glutamate binding; IEA:Ensembl.
DR GO; GO:0015501; F:glutamate:sodium symporter activity; IDA:UniProtKB.
DR GO; GO:0005314; F:high-affinity L-glutamate transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0005313; F:L-glutamate transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0015175; F:neutral amino acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0031223; P:auditory behavior; IEA:Ensembl.
DR GO; GO:0048667; P:cell morphogenesis involved in neuron differentiation; IEA:Ensembl.
DR GO; GO:0071314; P:cellular response to cocaine; IEA:Ensembl.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; IEA:Ensembl.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:1902476; P:chloride transmembrane transport; IDA:UniProtKB.
DR GO; GO:0021545; P:cranial nerve development; IEA:Ensembl.
DR GO; GO:0070779; P:D-aspartate import across plasma membrane; IDA:UniProtKB.
DR GO; GO:0009449; P:gamma-aminobutyric acid biosynthetic process; IEA:Ensembl.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0140009; P:L-aspartate import across plasma membrane; IDA:UniProtKB.
DR GO; GO:0051938; P:L-glutamate import; IDA:UniProtKB.
DR GO; GO:0098712; P:L-glutamate import across plasma membrane; IDA:UniProtKB.
DR GO; GO:0015813; P:L-glutamate transmembrane transport; IDA:UniProtKB.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl.
DR GO; GO:0006836; P:neurotransmitter transport; TAS:Reactome.
DR GO; GO:0001504; P:neurotransmitter uptake; TAS:ProtInc.
DR GO; GO:0050806; P:positive regulation of synaptic transmission; IEA:Ensembl.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0046677; P:response to antibiotic; IEA:Ensembl.
DR GO; GO:0009416; P:response to light stimulus; IEA:Ensembl.
DR GO; GO:0009611; P:response to wounding; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl.
DR GO; GO:0070633; P:transepithelial transport; ISS:ARUK-UCL.
DR GO; GO:0150104; P:transport across blood-brain barrier; ISS:ARUK-UCL.
DR Gene3D; 1.10.3860.10; -; 1.
DR InterPro; IPR001991; Na-dicarboxylate_symporter.
DR InterPro; IPR018107; Na-dicarboxylate_symporter_CS.
DR InterPro; IPR036458; Na:dicarbo_symporter_sf.
DR Pfam; PF00375; SDF; 1.
DR SUPFAM; SSF118215; SSF118215; 1.
DR PROSITE; PS00713; NA_DICARBOXYL_SYMP_1; 1.
DR PROSITE; PS00714; NA_DICARBOXYL_SYMP_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Amino-acid transport; Cell membrane;
KW Chloride; Disease variant; Glycoprotein; Membrane; Metal-binding;
KW Phosphoprotein; Potassium; Reference proteome; Sodium; Symport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..542
FT /note="Excitatory amino acid transporter 1"
FT /id="PRO_0000202057"
FT TOPO_DOM 1..47
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TRANSMEM 48..68
FT /note="Helical; Name=1"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TOPO_DOM 69..86
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TRANSMEM 87..108
FT /note="Helical; Name=2"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TOPO_DOM 109..122
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TRANSMEM 123..145
FT /note="Helical; Name=3"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TOPO_DOM 146..236
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TRANSMEM 237..260
FT /note="Helical; Name=4"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TOPO_DOM 261..269
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TRANSMEM 270..297
FT /note="Helical; Name=5"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TOPO_DOM 298..318
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TRANSMEM 319..340
FT /note="Helical; Name=6"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TOPO_DOM 341..345
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:28424515"
FT INTRAMEM 346..376
FT /note="Discontinuously helical"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TOPO_DOM 377..385
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TRANSMEM 386..412
FT /note="Helical; Name=7"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TOPO_DOM 413..425
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:28424515"
FT INTRAMEM 426..459
FT /note="Discontinuously helical"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TOPO_DOM 460..472
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TRANSMEM 473..494
FT /note="Helical; Name=8"
FT /evidence="ECO:0000305|PubMed:28424515"
FT TOPO_DOM 495..542
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:28424515"
FT BINDING 363..365
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000269|PubMed:28424515,
FT ECO:0007744|PDB:5LM4"
FT BINDING 394
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 396
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:28424515,
FT ECO:0007744|PDB:5LM4"
FT BINDING 398
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 402
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000269|PubMed:28424515,
FT ECO:0007744|PDB:5LM4"
FT BINDING 443..447
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000269|PubMed:28424515,
FT ECO:0007744|PDB:5LM4"
FT BINDING 476
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000269|PubMed:28424515,
FT ECO:0007744|PDB:5LM4"
FT BINDING 483
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000269|PubMed:28424515,
FT ECO:0007744|PDB:5LM4"
FT BINDING 483
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 487
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT MOD_RES 512
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 430..475
FT /note="SITATAASIGAAGIPQAGLVTMVIVLTSVGLPTDDITLIIAVDWFL -> R
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16042756"
FT /id="VSP_043913"
FT VARIANT 219
FT /note="E -> D (in dbSNP:rs2032892)"
FT /id="VAR_011877"
FT VARIANT 290
FT /note="P -> R (in EA6; dbSNP:rs137852619)"
FT /evidence="ECO:0000269|PubMed:16116111"
FT /id="VAR_031733"
FT MUTAGEN 363
FT /note="S->R: Loss of electrogenic glutamate transport.
FT Strongly decreased L-aspartate and L-glutamate uptake
FT combined with strongly increased permeability ot other
FT ions; when associated with M-477."
FT /evidence="ECO:0000269|PubMed:20477940"
FT MUTAGEN 477
FT /note="R->M: Strongly decreased L-aspartate and L-glutamate
FT uptake combined with strongly increased permeability ot
FT other ions; when associated with R-363."
FT /evidence="ECO:0000269|PubMed:20477940"
FT MUTAGEN 523
FT /note="Y->F: No effect on activity."
FT /evidence="ECO:0000269|PubMed:28032905"
FT CONFLICT 366
FT /note="S -> CT (in Ref. 1)"
FT /evidence="ECO:0000305"
FT HELIX 41..45
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 76..81
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 83..95
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 102..104
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 106..109
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 114..117
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 121..136
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 262..265
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 274..277
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 283..300
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 316..328
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 332..335
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 347..351
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 353..362
FT /evidence="ECO:0007829|PDB:5LM4"
FT TURN 365..367
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 369..377
FT /evidence="ECO:0007829|PDB:5LM4"
FT TURN 378..380
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 387..396
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 400..407
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 411..414
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 424..439
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 446..449
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 451..456
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 462..464
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 465..473
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 475..487
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 493..497
FT /evidence="ECO:0007829|PDB:5LM4"
FT HELIX 499..504
FT /evidence="ECO:0007829|PDB:5LM4"
SQ SEQUENCE 542 AA; 59572 MW; 6E9F62D35A3A5A29 CRC64;
MTKSNGEEPK MGGRMERFQQ GVRKRTLLAK KKVQNITKED VKSYLFRNAF VLLTVTAVIV
GTILGFTLRP YRMSYREVKY FSFPGELLMR MLQMLVLPLI ISSLVTGMAA LDSKASGKMG
MRAVVYYMTT TIIAVVIGII IVIIIHPGKG TKENMHREGK IVRVTAADAF LDLIRNMFPP
NLVEACFKQF KTNYEKRSFK VPIQANETLV GAVINNVSEA METLTRITEE LVPVPGSVNG
VNALGLVVFS MCFGFVIGNM KEQGQALREF FDSLNEAIMR LVAVIMWYAP VGILFLIAGK
IVEMEDMGVI GGQLAMYTVT VIVGLLIHAV IVLPLLYFLV TRKNPWVFIG GLLQALITAL
GTSSSSATLP ITFKCLEENN GVDKRVTRFV LPVGATINMD GTALYEALAA IFIAQVNNFE
LNFGQIITIS ITATAASIGA AGIPQAGLVT MVIVLTSVGL PTDDITLIIA VDWFLDRLRT
TTNVLGDSLG AGIVEHLSRH ELKNRDVEMG NSVIEENEMK KPYQLIAQDN ETEKPIDSET
KM
