ID EAA2_HUMAN Reviewed; 574 AA.
AC P43004; B4DQE9; Q14417; Q541G6; U3KQQ4;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 27-MAR-2024, entry version 201.
DE RecName: Full=Excitatory amino acid transporter 2 {ECO:0000305};
DE AltName: Full=Glutamate/aspartate transporter II;
DE AltName: Full=Sodium-dependent glutamate/aspartate transporter 2;
DE AltName: Full=Solute carrier family 1 member 2;
GN Name=SLC1A2 {ECO:0000312|HGNC:HGNC:10940};
GN Synonyms=EAAT2 {ECO:0000303|PubMed:7521911}, GLT1;
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, SUBCELLULAR LOCATION,
RP TRANSPORTER ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=8172925; DOI=10.1016/0005-2736(94)90192-9;
RA Shashidharan P., Wittenberg I., Plaitakis A.;
RT "Molecular cloning of human brain glutamate/aspartate transporter II.";
RL Biochim. Biophys. Acta 1191:393-396(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
RX PubMed=7522567; DOI=10.1016/0005-2736(94)90026-4;
RA Manfras B.J., Rudert W.A., Trucco M., Boehm B.O.;
RT "Cloning and characterization of a glutamate transporter cDNA from human
RT brain and pancreas.";
RL Biochim. Biophys. Acta 1195:185-188(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9463476; DOI=10.1124/mol.53.2.195;
RA Shimamoto K., Lebrun B., Yasuda-Kamatani Y., Sakaitani M., Shigeri Y.,
RA Yumoto N., Nakajima T.;
RT "DL-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino
RT acid transporters.";
RL Mol. Pharmacol. 53:195-201(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=12950454; DOI=10.1046/j.1471-4159.2003.01958.x;
RA Kim S.Y., Chao W., Choi S.Y., Volsky D.J.;
RT "Cloning and characterization of the 3'-untranslated region of the human
RT excitatory amino acid transporter 2 transcript.";
RL J. Neurochem. 86:1458-1467(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
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).
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 SUBCELLULAR LOCATION.
RX PubMed=14506254; DOI=10.1074/jbc.m307990200;
RA Melzer N., Biela A., Fahlke C.;
RT "Glutamate modifies ion conduction and voltage-dependent gating of
RT excitatory amino acid transporter-associated anion channels.";
RL J. Biol. Chem. 278:50112-50119(2003).
RN [11]
RP SUBUNIT, FUNCTION, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=15265858; DOI=10.1074/jbc.m408038200;
RA Gendreau S., Voswinkel S., Torres-Salazar D., Lang N., Heidtmann H.,
RA Detro-Dassen S., Schmalzing G., Hidalgo P., Fahlke C.;
RT "A trimeric quaternary structure is conserved in bacterial and human
RT glutamate transporters.";
RL J. Biol. Chem. 279:39505-39512(2004).
RN [12]
RP SUBUNIT.
RX PubMed=15483603; DOI=10.1038/nature03018;
RA Yernool D., Boudker O., Jin Y., Gouaux E.;
RT "Structure of a glutamate transporter homologue from Pyrococcus
RT horikoshii.";
RL Nature 431:811-818(2004).
RN [13]
RP ALTERNATIVE SPLICING (ISOFORM 3), AND SUBUNIT.
RX PubMed=20688910; DOI=10.1074/jbc.m110.153494;
RA Gebhardt F.M., Mitrovic A.D., Gilbert D.F., Vandenberg R.J., Lynch J.W.,
RA Dodd P.R.;
RT "Exon-skipping splice variants of excitatory amino acid transporter-2
RT (EAAT2) form heteromeric complexes with full-length EAAT2.";
RL J. Biol. Chem. 285:31313-31324(2010).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=26483543; DOI=10.1074/jbc.m115.689836;
RA Simonin A., Montalbetti N., Gyimesi G., Pujol-Gimenez J., Hediger M.A.;
RT "The Hydroxyl Side Chain of a Highly Conserved Serine Residue Is Required
RT for Cation Selectivity and Substrate Transport in the Glial Glutamate
RT Transporter GLT-1/SLC1A2.";
RL J. Biol. Chem. 290:30464-30474(2015).
RN [15]
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 [16]
RP INVOLVEMENT IN DEE41, AND VARIANTS DEE41 ARG-82 AND PRO-85.
RX PubMed=27476654; DOI=10.1016/j.ajhg.2016.06.003;
RG Epi4K Consortium;
RT "De novo mutations in SLC1A2 and CACNA1A are important causes of epileptic
RT encephalopathies.";
RL Am. J. Hum. Genet. 99:287-298(2016).
RN [17]
RP VARIANTS DEE41 ARG-82 AND ARG-289.
RX PubMed=28777935; DOI=10.1016/j.ajhg.2017.07.004;
RG Epilepsy Genomics Study;
RG Deciphering Developmental Disorders Study;
RA Guella I., McKenzie M.B., Evans D.M., Buerki S.E., Toyota E.B.,
RA Van Allen M.I., Suri M., Elmslie F., Simon M.E.H., van Gassen K.L.I.,
RA Heron D., Keren B., Nava C., Connolly M.B., Demos M., Farrer M.J.;
RT "De novo mutations in YWHAG cause early-onset epilepsy.";
RL Am. J. Hum. Genet. 101:300-310(2017).
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:14506254, PubMed:15265858, PubMed:26690923).
CC Functions as a symporter that transports one amino acid molecule
CC together with two or three Na(+) ions and one proton, in parallel with
CC the counter-transport of one K(+) ion (PubMed:14506254). Mediates Cl(-)
CC flux that is not coupled to amino acid transport; this avoids the
CC accumulation of negative charges due to aspartate and Na(+) symport
CC (PubMed:14506254). Essential for the rapid removal of released
CC glutamate from the synaptic cleft, and for terminating the postsynaptic
CC action of glutamate (By similarity). {ECO:0000250|UniProtKB:P43006,
CC ECO:0000269|PubMed:15265858, ECO:0000269|PubMed:26690923,
CC ECO:0000269|PubMed:7521911}.
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=97 uM for L-glutamate {ECO:0000269|PubMed:7521911};
CC KM=54 uM for D-aspartate {ECO:0000269|PubMed:7521911};
CC KM=18 uM for L-glutamate (when transfected in Xenopus laevis oocytes)
CC {ECO:0000269|PubMed:7521911};
CC KM=13 uM for D-aspartate (when transfected in Xenopus laevis oocytes)
CC {ECO:0000269|PubMed:7521911};
CC KM=7 uM for L-aspartate (when transfected in Xenopus laevis oocytes)
CC {ECO:0000269|PubMed:7521911};
CC KM=391 uM for L-glutamate (when transfected in Xenopus laevis
CC oocytes) {ECO:0000269|PubMed:26690923};
CC -!- SUBUNIT: Homotrimer (PubMed:15265858, PubMed:15483603,
CC PubMed:26483543). Isoform 3 can oligomerize with isoform 1
CC (PubMed:20688910). Interacts with AJUBA (By similarity).
CC {ECO:0000250|UniProtKB:P31596, ECO:0000269|PubMed:15265858,
CC ECO:0000269|PubMed:15483603, ECO:0000269|PubMed:20688910,
CC ECO:0000269|PubMed:26483543}.
CC -!- INTERACTION:
CC P43004; P42858: HTT; NbExp=12; IntAct=EBI-3440986, EBI-466029;
CC P43004; P10636: MAPT; NbExp=4; IntAct=EBI-3440986, EBI-366182;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14506254,
CC ECO:0000269|PubMed:15265858, ECO:0000269|PubMed:26690923,
CC ECO:0000269|PubMed:7521911}; Multi-pass membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P43004-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P43004-2; Sequence=VSP_037152;
CC Name=3; Synonyms=EEAT2b;
CC IsoId=P43004-3; Sequence=VSP_054934;
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:0000250|UniProtKB:P43003}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:15265858}.
CC -!- PTM: Palmitoylation at Cys-38 is not required for correct subcellular
CC localization, but is important for glutamate uptake activity.
CC {ECO:0000250|UniProtKB:P43006}.
CC -!- DISEASE: Developmental and epileptic encephalopathy 41 (DEE41)
CC [MIM:617105]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. DEE41 inheritance is autosomal dominant.
CC {ECO:0000269|PubMed:27476654, ECO:0000269|PubMed:28777935}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the dicarboxylate/amino acid:cation symporter
CC (DAACS) (TC 2.A.23) family. SLC1A2 subfamily. {ECO:0000305}.
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DR EMBL; U03505; AAA50429.1; -; mRNA.
DR EMBL; U01824; AAA18900.1; -; mRNA.
DR EMBL; Z32517; CAA83532.1; -; mRNA.
DR EMBL; D85884; BAA28706.1; -; mRNA.
DR EMBL; AY066021; AAL57716.1; -; mRNA.
DR EMBL; AK298769; BAG60911.1; -; mRNA.
DR EMBL; AC090625; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL133330; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW68143.1; -; Genomic_DNA.
DR EMBL; BC132768; AAI32769.1; -; mRNA.
DR CCDS; CCDS31459.1; -. [P43004-1]
DR CCDS; CCDS55756.1; -. [P43004-2]
DR PIR; I37426; I37426.
DR PIR; I38432; I38432.
DR RefSeq; NP_001182657.1; NM_001195728.2. [P43004-2]
DR RefSeq; NP_001239581.1; NM_001252652.1. [P43004-2]
DR RefSeq; NP_004162.2; NM_004171.3. [P43004-1]
DR PDB; 7VR7; EM; 2.80 A; A=1-574.
DR PDB; 7VR8; EM; 3.20 A; A=1-574.
DR PDB; 7XR4; EM; 3.40 A; A/B/C=1-574.
DR PDB; 7XR6; EM; 3.40 A; A/B/C=1-574.
DR PDBsum; 7VR7; -.
DR PDBsum; 7VR8; -.
DR PDBsum; 7XR4; -.
DR PDBsum; 7XR6; -.
DR AlphaFoldDB; P43004; -.
DR EMDB; EMD-32097; -.
DR EMDB; EMD-32098; -.
DR EMDB; EMD-33407; -.
DR EMDB; EMD-33408; -.
DR SMR; P43004; -.
DR BioGRID; 112397; 11.
DR CORUM; P43004; -.
DR IntAct; P43004; 5.
DR MINT; P43004; -.
DR STRING; 9606.ENSP00000278379; -.
DR BindingDB; P43004; -.
DR ChEMBL; CHEMBL4973; -.
DR DrugBank; DB08868; Fingolimod.
DR DrugBank; DB00142; Glutamic acid.
DR DrugCentral; P43004; -.
DR GuidetoPHARMACOLOGY; 869; -.
DR TCDB; 2.A.23.2.7; the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.
DR GlyCosmos; P43004; 2 sites, No reported glycans.
DR GlyGen; P43004; 2 sites.
DR iPTMnet; P43004; -.
DR PhosphoSitePlus; P43004; -.
DR SwissPalm; P43004; -.
DR BioMuta; SLC1A2; -.
DR DMDM; 3041668; -.
DR MassIVE; P43004; -.
DR PaxDb; 9606-ENSP00000278379; -.
DR PeptideAtlas; P43004; -.
DR ProteomicsDB; 55569; -. [P43004-1]
DR ProteomicsDB; 55570; -. [P43004-2]
DR Antibodypedia; 2179; 392 antibodies from 33 providers.
DR DNASU; 6506; -.
DR Ensembl; ENST00000278379.9; ENSP00000278379.3; ENSG00000110436.13. [P43004-1]
DR Ensembl; ENST00000395753.6; ENSP00000379102.1; ENSG00000110436.13. [P43004-2]
DR Ensembl; ENST00000643000.1; ENSP00000495164.1; ENSG00000110436.13. [P43004-2]
DR Ensembl; ENST00000643305.1; ENSP00000494828.1; ENSG00000110436.13. [P43004-3]
DR Ensembl; ENST00000644050.1; ENSP00000496123.1; ENSG00000110436.13. [P43004-2]
DR Ensembl; ENST00000644299.1; ENSP00000494669.1; ENSG00000110436.13. [P43004-2]
DR Ensembl; ENST00000645194.1; ENSP00000496093.1; ENSG00000110436.13. [P43004-2]
DR Ensembl; ENST00000645634.1; ENSP00000493945.1; ENSG00000110436.13. [P43004-2]
DR Ensembl; ENST00000647104.1; ENSP00000494025.1; ENSG00000110436.13. [P43004-2]
DR GeneID; 6506; -.
DR KEGG; hsa:6506; -.
DR MANE-Select; ENST00000278379.9; ENSP00000278379.3; NM_004171.4; NP_004162.2.
DR UCSC; uc001mwd.4; human. [P43004-1]
DR AGR; HGNC:10940; -.
DR CTD; 6506; -.
DR DisGeNET; 6506; -.
DR GeneCards; SLC1A2; -.
DR HGNC; HGNC:10940; SLC1A2.
DR HPA; ENSG00000110436; Tissue enriched (brain).
DR MalaCards; SLC1A2; -.
DR MIM; 600300; gene.
DR MIM; 617105; phenotype.
DR neXtProt; NX_P43004; -.
DR OpenTargets; ENSG00000110436; -.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR PharmGKB; PA35827; -.
DR VEuPathDB; HostDB:ENSG00000110436; -.
DR eggNOG; KOG3787; Eukaryota.
DR GeneTree; ENSGT00940000155379; -.
DR HOGENOM; CLU_019375_3_0_1; -.
DR InParanoid; P43004; -.
DR OMA; ICSFVVP; -.
DR OrthoDB; 49426at2759; -.
DR PhylomeDB; P43004; -.
DR TreeFam; TF315206; -.
DR PathwayCommons; P43004; -.
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 SignaLink; P43004; -.
DR SIGNOR; P43004; -.
DR BioGRID-ORCS; 6506; 10 hits in 1149 CRISPR screens.
DR ChiTaRS; SLC1A2; human.
DR GeneWiki; SLC1A2; -.
DR GenomeRNAi; 6506; -.
DR Pharos; P43004; Tchem.
DR PRO; PR:P43004; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P43004; Protein.
DR Bgee; ENSG00000110436; Expressed in endothelial cell and 177 other cell types or tissues.
DR ExpressionAtlas; P43004; baseline and differential.
DR Genevisible; P43004; HS.
DR GO; GO:0097449; C:astrocyte projection; ISS:ARUK-UCL.
DR GO; GO:0030673; C:axolemma; IEA:Ensembl.
DR GO; GO:0044297; C:cell body; ISS:ARUK-UCL.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0098796; C:membrane protein complex; IDA:ARUK-UCL.
DR GO; GO:0045121; C:membrane raft; IDA:ARUK-UCL.
DR GO; GO:0044306; C:neuron projection terminus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IMP:UniProtKB.
DR GO; GO:0042734; C:presynaptic membrane; IDA:SynGO.
DR GO; GO:0031982; C:vesicle; IEA:Ensembl.
DR GO; GO:0033229; F:cysteine transmembrane transporter activity; 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:0008509; F:monoatomic anion transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0015175; F:neutral L-amino acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0030534; P:adult behavior; IEA:Ensembl.
DR GO; GO:0071314; P:cellular response to cocaine; IEA:Ensembl.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; IEA:Ensembl.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0070779; P:D-aspartate import across plasma membrane; IDA:UniProtKB.
DR GO; GO:0006750; P:glutathione biosynthetic process; IEA:Ensembl.
DR GO; GO:0140009; P:L-aspartate import across plasma membrane; IDA:UniProtKB.
DR GO; GO:0070778; P:L-aspartate transmembrane transport; ISS:ARUK-UCL.
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:0006811; P:monoatomic ion transport; TAS:Reactome.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0098810; P:neurotransmitter reuptake; IEA:Ensembl.
DR GO; GO:0006836; P:neurotransmitter transport; TAS:Reactome.
DR GO; GO:0046326; P:positive regulation of glucose import; IEA:Ensembl.
DR GO; GO:0070207; P:protein homotrimerization; IDA:UniProtKB.
DR GO; GO:0043200; P:response to amino acid; 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:0021537; P:telencephalon development; 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 GO; GO:0007632; P:visual behavior; IEA:Ensembl.
DR Gene3D; 1.10.3860.10; Sodium:dicarboxylate symporter; 1.
DR InterPro; IPR001991; Na-dicarboxylate_symporter.
DR InterPro; IPR018107; Na-dicarboxylate_symporter_CS.
DR InterPro; IPR036458; Na:dicarbo_symporter_sf.
DR PANTHER; PTHR11958:SF93; EXCITATORY AMINO ACID TRANSPORTER 2; 1.
DR PANTHER; PTHR11958; SODIUM/DICARBOXYLATE SYMPORTER-RELATED; 1.
DR Pfam; PF00375; SDF; 1.
DR PRINTS; PR00173; EDTRNSPORT.
DR SUPFAM; SSF118215; Proton glutamate symport protein; 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; Epilepsy; Glycoprotein; Lipoprotein; Membrane;
KW Metal-binding; Palmitate; Phosphoprotein; Potassium; Reference proteome;
KW Sodium; Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..574
FT /note="Excitatory amino acid transporter 2"
FT /id="PRO_0000202061"
FT TOPO_DOM 1..44
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 45..64
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 65..87
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 88..108
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 109..120
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 121..142
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 143..235
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 236..259
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 260..268
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 269..296
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 297..317
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 318..339
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 340..344
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 345..375
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 376..384
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 385..411
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 412..424
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 425..458
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 459..471
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 472..493
FT /note="Helical; Name=8"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 494..574
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT BINDING 362..364
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 393
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 395
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 397
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 401
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 442..446
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 475
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 482
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 482
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 486
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT MOD_RES 3
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31596"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31596"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31596"
FT MOD_RES 506
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43006"
FT MOD_RES 521
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43006"
FT MOD_RES 532
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43006"
FT MOD_RES 534
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43006"
FT MOD_RES 539
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43006"
FT MOD_RES 544
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43006"
FT MOD_RES 560
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43006"
FT MOD_RES 564
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43006"
FT LIPID 38
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P43006"
FT CARBOHYD 206
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 216
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..9
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8172925"
FT /id="VSP_037152"
FT VAR_SEQ 553..574
FT /note="TLAANGKSADCSVEEEPWKREK -> HFPFMDIETCI (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054934"
FT VARIANT 82
FT /note="G -> R (in DEE41; dbSNP:rs886037942)"
FT /evidence="ECO:0000269|PubMed:27476654,
FT ECO:0000269|PubMed:28777935"
FT /id="VAR_077083"
FT VARIANT 85
FT /note="L -> P (in DEE41; dbSNP:rs886037943)"
FT /evidence="ECO:0000269|PubMed:27476654"
FT /id="VAR_077084"
FT VARIANT 289
FT /note="P -> R (in DEE41; dbSNP:rs781379291)"
FT /evidence="ECO:0000269|PubMed:28777935"
FT /id="VAR_080229"
FT CONFLICT 7
FT /note="A -> T (in Ref. 6; BAG60911)"
FT /evidence="ECO:0000305"
FT CONFLICT 19
FT /note="H -> P (in Ref. 1; AAA50429)"
FT /evidence="ECO:0000305"
FT CONFLICT 27
FT /note="E -> G (in Ref. 3; CAA83532)"
FT /evidence="ECO:0000305"
FT CONFLICT 50
FT /note="T -> Q (in Ref. 2; AAA18900)"
FT /evidence="ECO:0000305"
FT CONFLICT 58
FT /note="A -> S (in Ref. 2; AAA18900)"
FT /evidence="ECO:0000305"
FT CONFLICT 141
FT /note="A -> G (in Ref. 3; CAA83532)"
FT /evidence="ECO:0000305"
FT CONFLICT 155
FT /note="P -> A (in Ref. 3; CAA83532)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="V -> E (in Ref. 1; AAA50429)"
FT /evidence="ECO:0000305"
FT CONFLICT 253..255
FT /note="GIA -> AIP (in Ref. 3; CAA83532)"
FT /evidence="ECO:0000305"
FT CONFLICT 263..289
FT /note="AKLMVDFFNILNEIVMKLVIMIMWYSP -> GQADGGFLQHFERDCNEVSDH
FT DHVVLS (in Ref. 3; CAA83532)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="F -> L (in Ref. 1; AAA50429)"
FT /evidence="ECO:0000305"
FT CONFLICT 539
FT /note="Y -> F (in Ref. 3; CAA83532)"
FT /evidence="ECO:0000305"
FT CONFLICT 556
FT /note="A -> G (in Ref. 3; CAA83532)"
FT /evidence="ECO:0000305"
FT CONFLICT 563..565
FT /note="CSV -> RVL (in Ref. 3; CAA83532)"
FT /evidence="ECO:0000305"
FT CONFLICT 570
FT /note="W -> G (in Ref. 3; CAA83532)"
FT /evidence="ECO:0000305"
FT HELIX 38..43
FT /evidence="ECO:0007829|PDB:7XR4"
FT HELIX 45..67
FT /evidence="ECO:0007829|PDB:7VR7"
FT HELIX 72..107
FT /evidence="ECO:0007829|PDB:7VR7"
FT HELIX 110..113
FT /evidence="ECO:0007829|PDB:7XR4"
FT HELIX 115..142
FT /evidence="ECO:0007829|PDB:7VR7"
FT TURN 144..147
FT /evidence="ECO:0007829|PDB:7XR4"
FT HELIX 164..175
FT /evidence="ECO:0007829|PDB:7VR7"
FT HELIX 180..185
FT /evidence="ECO:0007829|PDB:7VR7"
FT STRAND 186..192
FT /evidence="ECO:0007829|PDB:7VR7"
FT STRAND 232..239
FT /evidence="ECO:0007829|PDB:7VR7"
FT HELIX 242..257
FT /evidence="ECO:0007829|PDB:7VR7"
FT HELIX 258..263
FT /evidence="ECO:0007829|PDB:7VR7"
FT HELIX 264..286
FT /evidence="ECO:0007829|PDB:7VR7"
FT HELIX 288..302
FT /evidence="ECO:0007829|PDB:7VR7"
FT HELIX 306..329
FT /evidence="ECO:0007829|PDB:7VR7"
FT HELIX 331..340
FT /evidence="ECO:0007829|PDB:7VR7"
FT HELIX 344..361
FT /evidence="ECO:0007829|PDB:7VR7"
FT TURN 364..366
FT /evidence="ECO:0007829|PDB:7VR7"
FT HELIX 368..377
FT /evidence="ECO:0007829|PDB:7VR7"
FT HELIX 383..396
FT /evidence="ECO:0007829|PDB:7VR7"
FT HELIX 399..415
FT /evidence="ECO:0007829|PDB:7VR7"
FT HELIX 422..441
FT /evidence="ECO:0007829|PDB:7VR7"
FT HELIX 446..456
FT /evidence="ECO:0007829|PDB:7VR7"
FT HELIX 461..463
FT /evidence="ECO:0007829|PDB:7XR4"
FT HELIX 464..496
FT /evidence="ECO:0007829|PDB:7VR7"
FT HELIX 498..506
FT /evidence="ECO:0007829|PDB:7XR4"
SQ SEQUENCE 574 AA; 62104 MW; C8104E6727979435 CRC64;
MASTEGANNM PKQVEVRMHD SHLGSEEPKH RHLGLRLCDK LGKNLLLTLT VFGVILGAVC
GGLLRLASPI HPDVVMLIAF PGDILMRMLK MLILPLIISS LITGLSGLDA KASGRLGTRA
MVYYMSTTII AAVLGVILVL AIHPGNPKLK KQLGPGKKND EVSSLDAFLD LIRNLFPENL
VQACFQQIQT VTKKVLVAPP PDEEANATSA VVSLLNETVT EVPEETKMVI KKGLEFKDGM
NVLGLIGFFI AFGIAMGKMG DQAKLMVDFF NILNEIVMKL VIMIMWYSPL GIACLICGKI
IAIKDLEVVA RQLGMYMVTV IIGLIIHGGI FLPLIYFVVT RKNPFSFFAG IFQAWITALG
TASSAGTLPV TFRCLEENLG IDKRVTRFVL PVGATINMDG TALYEAVAAI FIAQMNGVVL
DGGQIVTVSL TATLASVGAA SIPSAGLVTM LLILTAVGLP TEDISLLVAV DWLLDRMRTS
VNVVGDSFGA GIVYHLSKSE LDTIDSQHRV HEDIEMTKTQ SIYDDMKNHR ESNSNQCVYA
AHNSVIVDEC KVTLAANGKS ADCSVEEEPW KREK
//
