EAA2_RAT
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 03-AUG-2022, entry version 167.
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};
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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 GlyGen; P31596; 2 sites, 8 N-linked glycans (1 site).
DR iPTMnet; P31596; -.
DR PhosphoSitePlus; P31596; -.
DR SwissPalm; 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 InParanoid; P31596; -.
DR OrthoDB; 1184392at2759; -.
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:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0099056; C:integral component of presynaptic membrane; 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:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0044306; C:neuron projection terminus; ISO: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:0031982; C:vesicle; ISO:RGD.
DR GO; GO:0008509; F:anion transmembrane transporter activity; 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:0015175; F:neutral amino acid transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0030534; P:adult behavior; ISO:RGD.
DR GO; GO:0098656; P:anion transmembrane transport; 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: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:0010259; P:multicellular organism aging; 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; -; 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 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
