ID EAA2_RAT Reviewed; 573 AA. AC P31596; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1993, sequence version 2. DT 13-SEP-2023, entry version 172. DE RecName: Full=Excitatory amino acid transporter 2; DE AltName: Full=GLT-1 {ECO:0000303|PubMed:11860269, ECO:0000303|PubMed:1448170}; DE AltName: Full=Sodium-dependent glutamate/aspartate transporter 2; DE Short=GLUT-R; DE AltName: Full=Solute carrier family 1 member 2; GN Name=Slc1a2; Synonyms=Eaat2, Glt1; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, AND TRANSPORTER ACTIVITY. RC TISSUE=Brain; RX PubMed=1448170; DOI=10.1038/360464a0; RA Pines G., Danbolt N.C., Bjoeraas M., Zhang Y., Bendahan A., Eide L., RA Koepsell H., Storm-Mathisen J., Seeberg E., Kanner B.I.; RT "Cloning and expression of a rat brain L-glutamate transporter."; RL Nature 360:464-467(1992). RN [2] RP ERRATUM OF PUBMED:1448170. RA Pines G., Danbolt N.C., Bjoeraas M., Zhang Y., Bendahan A., Eide L., RA Koepsell H., Storm-Mathisen J., Seeberg E., Kanner B.I.; RL Nature 360:768-768(1992). RN [3] RP SEQUENCE REVISION TO 260-289. RX PubMed=8099882; DOI=10.1016/0014-5793(93)81421-u; RA Kanner B.I.; RT "Glutamate transporters from brain. A novel neurotransmitter transporter RT family."; RL FEBS Lett. 325:95-99(1993). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Forebrain; RA Roginski R.S., Choudhury K., Meiners S., Marone M., Basma A.N., RA Geller H.M.; RL Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GLT-1A). RC TISSUE=Hepatoma; RX PubMed=11068035; DOI=10.1016/s0014-5793(00)02114-1; RA Pollard M., McGivan J.; RT "The rat hepatoma cell line H4-II-E-C3 expresses high activities of the RT high-affinity glutamate transporter GLT-1A."; RL FEBS Lett. 484:74-76(2000). RN [6] RP PROTEIN SEQUENCE OF 158-173, AND IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=Sprague-Dawley; TISSUE=Brain; RA Lubec G., Kang S.U.; RL Submitted (JUL-2007) to UniProtKB. RN [7] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-298 AND HIS-326. RX PubMed=7913472; DOI=10.1016/s0021-9258(17)32207-x; RA Zhang Y., Pines G., Kanner B.I.; RT "Histidine 326 is critical for the function of GLT-1, a (Na+ + K+)-coupled RT glutamate transporter from rat brain."; RL J. Biol. Chem. 269:19573-19577(1994). RN [8] RP INTERACTION WITH AJUBA. RX PubMed=11860269; DOI=10.1006/mcne.2001.1066; RA Marie H., Billups D., Bedford F.K., Dumoulin A., Goyal R.K., Longmore G.D., RA Moss S.J., Attwell D.; RT "The amino terminus of the glial glutamate transporter GLT-1 interacts with RT the LIM protein Ajuba."; RL Mol. Cell. Neurosci. 19:152-164(2002). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3; SER-21; SER-24; SER-25 AND RP SER-505, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). 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:1448170, PubMed:7913472). 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:1448170). 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 (By similarity). Essential for the rapid CC removal of released glutamate from the synaptic cleft, and for CC terminating the postsynaptic action of glutamate (By similarity). CC {ECO:0000250|UniProtKB:P43004, ECO:0000250|UniProtKB:P43006, CC ECO:0000269|PubMed:1448170, ECO:0000269|PubMed:7913472}. 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:1448170}; 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:0000250|UniProtKB:P43005}; 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:0000250|UniProtKB:P43004}; CC -!- SUBUNIT: Homotrimer (By similarity). Interacts with AJUBA CC (PubMed:11860269). {ECO:0000250|UniProtKB:P43004, CC ECO:0000269|PubMed:11860269}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1448170, CC ECO:0000269|PubMed:7913472}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P43004}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Glt1; CC IsoId=P31596-1; Sequence=Displayed; CC Name=Glt-1A; CC IsoId=P31596-2; Sequence=VSP_006266; CC -!- TISSUE SPECIFICITY: Localized in brain and is highly enriched in the CC Purkinje cell layer in cerebellum. {ECO:0000269|PubMed:1448170}. 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:0000250|UniProtKB:P43006}. 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 -!- SIMILARITY: Belongs to the dicarboxylate/amino acid:cation symporter CC (DAACS) (TC 2.A.23) family. SLC1A2 subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA93062.1; Type=Erroneous initiation; 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; X67857; CAA48042.1; ALT_SEQ; mRNA. DR EMBL; U15098; AAA93061.1; -; mRNA. DR EMBL; U15098; AAA93062.1; ALT_INIT; mRNA. DR EMBL; AF297648; AAG13411.1; -; mRNA. DR PIR; S28901; S28901. DR RefSeq; NP_001289018.1; NM_001302089.1. DR RefSeq; NP_058911.2; NM_017215.2. DR AlphaFoldDB; P31596; -. DR SMR; P31596; -. DR BioGRID; 248124; 4. DR CORUM; P31596; -. DR IntAct; P31596; 3. DR MINT; P31596; -. DR STRING; 10116.ENSRNOP00000007604; -. DR ChEMBL; CHEMBL2900; -. DR GuidetoPHARMACOLOGY; 869; -. DR TCDB; 2.A.23.2.2; the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family. DR CarbonylDB; P31596; -. DR GlyCosmos; P31596; 2 sites, 8 glycans. DR GlyGen; P31596; 2 sites, 21 N-linked glycans (2 sites). DR iPTMnet; P31596; -. DR PhosphoSitePlus; P31596; -. DR SwissPalm; P31596; -. DR PaxDb; P31596; -. DR GeneID; 29482; -. DR KEGG; rno:29482; -. DR UCSC; RGD:3697; rat. [P31596-1] DR AGR; RGD:3697; -. DR CTD; 6506; -. DR RGD; 3697; Slc1a2. DR eggNOG; KOG3787; Eukaryota. DR InParanoid; P31596; -. DR OrthoDB; 49426at2759; -. DR PhylomeDB; P31596; -. DR TreeFam; TF315206; -. DR Reactome; R-RNO-210455; Astrocytic Glutamate-Glutamine Uptake And Metabolism. DR Reactome; R-RNO-210500; Glutamate Neurotransmitter Release Cycle. DR Reactome; R-RNO-425393; Transport of inorganic cations/anions and amino acids/oligopeptides. DR PRO; PR:P31596; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0097449; C:astrocyte projection; IDA:ARUK-UCL. DR GO; GO:0030673; C:axolemma; ISO:RGD. DR GO; GO:0030424; C:axon; ISO:RGD. DR GO; GO:0044297; C:cell body; IDA:ARUK-UCL. DR GO; GO:0009986; C:cell surface; ISO:RGD. DR GO; GO:0043198; C:dendritic shaft; IDA:RGD. DR GO; GO:0043197; C:dendritic spine; IDA:RGD. DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD. DR GO; GO:0016020; C:membrane; ISO:RGD. DR GO; GO:0098796; C:membrane protein complex; IDA:ARUK-UCL. DR GO; GO:0045121; C:membrane raft; ISO:RGD. DR GO; GO:0044306; C:neuron projection terminus; ISO:RGD. DR GO; GO:0005886; C:plasma membrane; IMP:UniProtKB. DR GO; GO:0098793; C:presynapse; ISO:RGD. DR GO; GO:0042734; C:presynaptic membrane; IDA:RGD. DR GO; GO:0045202; C:synapse; ISO:RGD. DR GO; GO:0031982; C:vesicle; ISO:RGD. DR GO; GO:0033229; F:cysteine transmembrane transporter activity; ISO:RGD. 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; ISO:RGD. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0008509; F:monoatomic anion transmembrane transporter activity; ISO:RGD. DR GO; GO:0015175; F:neutral L-amino acid transmembrane transporter activity; IBA:GO_Central. DR GO; GO:0030534; P:adult behavior; ISO:RGD. DR GO; GO:0071314; P:cellular response to cocaine; ISO:RGD. DR GO; GO:0031668; P:cellular response to extracellular stimulus; ISO:RGD. DR GO; GO:0070779; P:D-aspartate import across plasma membrane; ISO:RGD. DR GO; GO:0006750; P:glutathione biosynthetic process; ISO:RGD. DR GO; GO:0140009; P:L-aspartate import across plasma membrane; ISO:RGD. DR GO; GO:0070778; P:L-aspartate transmembrane transport; IBA:GO_Central. DR GO; GO:0098712; P:L-glutamate import across plasma membrane; ISS:UniProtKB. DR GO; GO:0015813; P:L-glutamate transmembrane transport; IMP:RGD. DR GO; GO:0098656; P:monoatomic anion transmembrane transport; ISO:RGD. DR GO; GO:0035264; P:multicellular organism growth; ISO:RGD. DR GO; GO:0007399; P:nervous system development; ISO:RGD. DR GO; GO:0098810; P:neurotransmitter reuptake; ISO:RGD. DR GO; GO:0006836; P:neurotransmitter transport; TAS:RGD. DR GO; GO:0046326; P:positive regulation of glucose import; ISO:RGD. DR GO; GO:0070207; P:protein homotrimerization; ISS:UniProtKB. DR GO; GO:0043200; P:response to amino acid; ISO:RGD. DR GO; GO:0009416; P:response to light stimulus; ISO:RGD. DR GO; GO:0009611; P:response to wounding; ISO:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:RGD. DR GO; GO:0021537; P:telencephalon development; ISO:RGD. DR GO; GO:0007632; P:visual behavior; ISO:RGD. 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 Alternative splicing; Amino-acid transport; Cell membrane; Chloride; KW Direct protein sequencing; Glycoprotein; Lipoprotein; Membrane; KW Metal-binding; Palmitate; Phosphoprotein; Potassium; Reference proteome; KW Sodium; Symport; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..573 FT /note="Excitatory amino acid transporter 2" FT /id="PRO_0000202063" FT TOPO_DOM 1..44 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 45..64 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 88..108 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 121..142 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 235..258 FT /note="Helical; Name=4" FT /evidence="ECO:0000250|UniProtKB:P43003" FT TRANSMEM 268..295 FT /note="Helical; Name=5" FT /evidence="ECO:0000250|UniProtKB:P43003" FT TRANSMEM 317..338 FT /note="Helical; Name=6" FT /evidence="ECO:0000250|UniProtKB:P43003" FT INTRAMEM 344..374 FT /note="Discontinuously helical" FT /evidence="ECO:0000250|UniProtKB:P43003" FT TRANSMEM 384..410 FT /note="Helical; Name=7" FT /evidence="ECO:0000250|UniProtKB:P43003" FT INTRAMEM 424..457 FT /note="Discontinuously helical" FT /evidence="ECO:0000250|UniProtKB:P43003" FT TRANSMEM 471..492 FT /note="Helical; Name=8" FT /evidence="ECO:0000250|UniProtKB:P43003" FT REGION 1..29 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 15..29 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 361..363 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT /evidence="ECO:0000250|UniProtKB:P43003" FT BINDING 392 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:O59010" FT BINDING 394 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P43003" FT BINDING 396 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:O59010" FT BINDING 400 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT /evidence="ECO:0000250|UniProtKB:P43003" FT BINDING 441..445 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT /evidence="ECO:0000250|UniProtKB:P43003" FT BINDING 474 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT /evidence="ECO:0000250|UniProtKB:P43003" FT BINDING 481 FT /ligand="L-aspartate" FT /ligand_id="ChEBI:CHEBI:29991" FT /evidence="ECO:0000250|UniProtKB:P43003" FT BINDING 481 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:O59010" FT BINDING 485 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:0007744|PubMed:22673903" FT MOD_RES 21 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 24 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 25 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 505 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 520 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P43006" FT MOD_RES 531 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P43006" FT MOD_RES 533 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P43006" FT MOD_RES 538 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P43006" FT MOD_RES 543 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P43006" FT MOD_RES 559 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P43006" FT MOD_RES 563 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 205 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 215 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 1..6 FT /note="MASTEG -> MVS (in isoform Glt-1A)" FT /evidence="ECO:0000303|PubMed:11068035" FT /id="VSP_006266" FT MUTAGEN 298 FT /note="K->H,R: Normal transporter activity." FT /evidence="ECO:0000269|PubMed:7913472" FT MUTAGEN 298 FT /note="K->N,T: Reduced transporter activity." FT /evidence="ECO:0000269|PubMed:7913472" FT MUTAGEN 326 FT /note="H->N,T,K,R: No transporter activity." FT /evidence="ECO:0000269|PubMed:7913472" FT CONFLICT 521 FT /note="V -> I (in Ref. 4; AAA93061/AAA93062)" FT /evidence="ECO:0000305" SQ SEQUENCE 573 AA; 62106 MW; 8C51D30954E00E7F CRC64; MASTEGANNM PKQVEVRMHD SHLSSEEPKH RNLGMRMCDK LGKNLLLSLT VFGVILGAVC GGLLRLAAPI HPDVVMLIAF PGDILMRMLK MLILPLIISS LITGLSGLDA KASGRLGTRA MVYYMSTTII AAVLGVILVL AIHPGNPKLK KQLGPGKKND EVSSLDAFLD LIRNLFPENL VQACFQQIQT VTKKVLVAPP SEEANTTKAV ISLLNETMNE APEETKIVIK KGLEFKDGMN VLGLIGFFIA FGIAMGKMGE QAKLMVEFFN ILNEIVMKLV IMIMWYSPLG IACLICGKII AIKDLEVVAR QLGMYMITVI VGLIIHGGIF LPLIYFVVTR KNPFSFFAGI FQAWITALGT ASSAGTLPVT FRCLEDNLGI DKRVTRFVLP VGATINMDGT ALYEAVAAIF IAQMNGVILD GGQIVTVSLT ATLASIGAAS IPSAGLVTML LILTAVGLPT EDISLLVAVD WLLDRMRTSV NVVGDSFGAG IVYHLSKSEL DTIDSQHRMH EDIEMTKTQS VYDDTKNHRE SNSNQCVYAA HNSVVIDECK VTLAANGKSA DCSVEEEPWK REK //