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 16-JAN-2019, entry version 150. 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; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; OC Muroidea; Muridae; Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. 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. 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 RT transporter 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 RT the 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 RP HIS-326. RX PubMed=7913472; RA Zhang Y., Pines G., Kanner B.I.; RT "Histidine 326 is critical for the function of GLT-1, a (Na+ + K+)- RT coupled 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., RA Longmore G.D., Moss S.J., Attwell D.; RT "The amino terminus of the glial glutamate transporter GLT-1 interacts RT with 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; RP SER-25 AND SER-505, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., RA Lundby C., Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 RT different rat organs and tissues."; RL Nat. Commun. 3:876-876(2012). CC -!- FUNCTION: Sodium-dependent, high-affinity amino acid transporter CC that mediates the uptake of L-glutamate and also L-aspartate and CC D-aspartate (PubMed:1448170, PubMed:7913472). Functions as a CC symporter that transports one amino acid molecule together with CC two or three Na(+) ions and one proton, in parallel with the CC counter-transport of one K(+) ion (PubMed:1448170). 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(+) CC symport (By similarity). Essential for the rapid removal of CC released glutamate from the synaptic cleft, and for terminating CC 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 -!- 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 CC the Purkinje cell layer in cerebellum. CC {ECO:0000269|PubMed:1448170}. CC -!- DOMAIN: Contains eight transmembrane regions plus two helical CC hairpins that dip into the membrane. These helical hairpin CC structures play an important role in the transport process. The CC first enters the membrane from the cytoplasmic side, the second CC one from the extracellular side. During the transport cycle, the CC regions involved in amino acid transport, and especially the CC helical hairpins, move vertically by about 15-18 Angstroms, CC alternating between exposure to the aqueous phase and reinsertion CC in the lipid bilayer. In contrast, the regions involved in CC 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 CC subcellular localization, but is important for glutamate uptake CC activity. {ECO:0000250|UniProtKB:P43006}. CC -!- SIMILARITY: Belongs to the dicarboxylate/amino acid:cation CC symporter (DAACS) (TC 2.A.23) family. SLC1A2 subfamily. CC {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 UniGene; Rn.10240; -. DR ProteinModelPortal; P31596; -. DR BioGrid; 248124; 2. DR CORUM; P31596; -. DR IntAct; P31596; 1. 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 iPTMnet; P31596; -. DR PhosphoSitePlus; P31596; -. DR SwissPalm; P31596; -. DR UniCarbKB; P31596; -. DR PaxDb; P31596; -. DR PRIDE; P31596; -. DR GeneID; 29482; -. DR KEGG; rno:29482; -. DR UCSC; RGD:3697; rat. [P31596-1] DR CTD; 6506; -. DR RGD; 3697; Slc1a2. DR eggNOG; KOG3787; Eukaryota. DR eggNOG; COG1301; LUCA. DR HOGENOM; HOG000208776; -. DR HOVERGEN; HBG000080; -. DR InParanoid; P31596; -. DR KO; K05613; -. DR OrthoDB; 1184392at2759; -. DR PhylomeDB; P31596; -. DR TreeFam; TF315206; -. DR PRO; PR:P31596; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0043198; C:dendritic shaft; IDA:RGD. DR GO; GO:0043197; C:dendritic spine; IDA:RGD. DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB. DR GO; GO:0043005; C:neuron projection; IDA:RGD. DR GO; GO:0005886; C:plasma membrane; IDA:RGD. DR GO; GO:0042734; C:presynaptic membrane; IDA:RGD. DR GO; GO:0045202; C:synapse; IDA:RGD. DR GO; GO:0015501; F:glutamate:sodium symporter activity; IDA:UniProtKB. DR GO; GO:0005314; F:high-affinity glutamate transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. 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:0006836; P:neurotransmitter transport; TAS:RGD. DR GO; GO:0070207; P:protein homotrimerization; ISS:UniProtKB. DR Gene3D; 1.10.3860.10; -; 2. 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 Alternative splicing; Amino-acid transport; Cell membrane; Chloride; KW Complete proteome; Direct protein sequencing; Glycoprotein; KW Lipoprotein; Membrane; Metal-binding; Palmitate; Phosphoprotein; KW Potassium; Reference proteome; Sodium; Symport; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1 573 Excitatory amino acid transporter 2. FT /FTId=PRO_0000202063. FT TOPO_DOM 1 44 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 45 64 Helical. {ECO:0000255}. FT TRANSMEM 88 108 Helical. {ECO:0000255}. FT TRANSMEM 121 142 Helical. {ECO:0000255}. FT TRANSMEM 235 258 Helical; Name=4. FT {ECO:0000250|UniProtKB:P43003}. FT TRANSMEM 268 295 Helical; Name=5. FT {ECO:0000250|UniProtKB:P43003}. FT TRANSMEM 317 338 Helical; Name=6. FT {ECO:0000250|UniProtKB:P43003}. FT INTRAMEM 344 374 Discontinuously helical. FT {ECO:0000250|UniProtKB:P43003}. FT TRANSMEM 384 410 Helical; Name=7. FT {ECO:0000250|UniProtKB:P43003}. FT INTRAMEM 424 457 Discontinuously helical. FT {ECO:0000250|UniProtKB:P43003}. FT TRANSMEM 471 492 Helical; Name=8. FT {ECO:0000250|UniProtKB:P43003}. FT REGION 361 363 Aspartate binding. FT {ECO:0000250|UniProtKB:P43003}. FT REGION 441 445 Aspartate binding. FT {ECO:0000250|UniProtKB:P43003}. FT METAL 392 392 Sodium 1; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:O59010}. FT METAL 394 394 Sodium 2; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:P43003}. FT METAL 396 396 Sodium 1. {ECO:0000250|UniProtKB:O59010}. FT METAL 481 481 Sodium 1; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:O59010}. FT METAL 485 485 Sodium 1. {ECO:0000250|UniProtKB:O59010}. FT BINDING 400 400 Aspartate. FT {ECO:0000250|UniProtKB:P43003}. FT BINDING 474 474 Aspartate. FT {ECO:0000250|UniProtKB:P43003}. FT BINDING 481 481 Aspartate. FT {ECO:0000250|UniProtKB:P43003}. FT MOD_RES 3 3 Phosphoserine. FT {ECO:0000244|PubMed:22673903}. FT MOD_RES 21 21 Phosphoserine. FT {ECO:0000244|PubMed:22673903}. FT MOD_RES 24 24 Phosphoserine. FT {ECO:0000244|PubMed:22673903}. FT MOD_RES 25 25 Phosphoserine. FT {ECO:0000244|PubMed:22673903}. FT MOD_RES 505 505 Phosphoserine. FT {ECO:0000244|PubMed:22673903}. FT MOD_RES 520 520 Phosphoserine. FT {ECO:0000250|UniProtKB:P43006}. FT MOD_RES 531 531 Phosphoserine. FT {ECO:0000250|UniProtKB:P43006}. FT MOD_RES 533 533 Phosphoserine. FT {ECO:0000250|UniProtKB:P43006}. FT MOD_RES 538 538 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43006}. FT MOD_RES 543 543 Phosphoserine. FT {ECO:0000250|UniProtKB:P43006}. FT MOD_RES 559 559 Phosphoserine. FT {ECO:0000250|UniProtKB:P43006}. FT MOD_RES 563 563 Phosphoserine. FT {ECO:0000250|UniProtKB:P43006}. FT LIPID 38 38 S-palmitoyl cysteine. FT {ECO:0000250|UniProtKB:P43006}. FT CARBOHYD 205 205 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 215 215 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT VAR_SEQ 1 6 MASTEG -> MVS (in isoform Glt-1A). FT {ECO:0000303|PubMed:11068035}. FT /FTId=VSP_006266. FT MUTAGEN 298 298 K->H,R: Normal transporter activity. FT {ECO:0000269|PubMed:7913472}. FT MUTAGEN 298 298 K->N,T: Reduced transporter activity. FT {ECO:0000269|PubMed:7913472}. FT MUTAGEN 326 326 H->N,T,K,R: No transporter activity. FT {ECO:0000269|PubMed:7913472}. FT CONFLICT 521 521 V -> I (in Ref. 4; AAA93061/AAA93062). FT {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 //