EAA1_RAT
ID EAA1_RAT Reviewed; 543 AA.
AC P24942; Q9JK43;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Excitatory amino acid transporter 1;
DE AltName: Full=Glial glutamate transporter;
DE AltName: Full=Sodium-dependent glutamate/aspartate transporter 1 {ECO:0000303|PubMed:11086157};
DE Short=GLAST {ECO:0000303|PubMed:1279699};
DE Short=GLAST-1 {ECO:0000303|PubMed:11086157};
DE AltName: Full=Solute carrier family 1 member 3;
GN Name=Slc1a3; Synonyms=Eaat1;
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, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=1279699; DOI=10.1073/pnas.89.22.10955;
RA Storck T., Schulte S., Hofmann K.O., Stoffel W.;
RT "Structure, expression, and functional analysis of a Na(+)-dependent
RT glutamate/aspartate transporter from rat brain.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:10955-10959(1992).
RN [2]
RP SEQUENCE REVISION TO 16.
RA Hofmann K.O.;
RL Submitted (JUN-1992) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=8387171; DOI=10.1016/0168-0102(93)90082-2;
RA Tanaka K.;
RT "Expression cloning of a rat glutamate transporter.";
RL Neurosci. Res. 16:149-153(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT VAL-302, AND
RP ALTERNATIVE SPLICING.
RC STRAIN=Wistar; TISSUE=Bone, and Cerebellum;
RX PubMed=11086157; DOI=10.1016/s0014-5793(00)02175-x;
RA Huggett J., Vaughan-Thomas A., Mason D.;
RT "The open reading frame of the Na(+)-dependent glutamate transporter GLAST-
RT 1 is expressed in bone and a splice variant of this molecule is expressed
RT in bone and brain.";
RL FEBS Lett. 485:13-18(2000).
RN [5]
RP PROTEIN SEQUENCE OF 18-23; 115-121; 159-170; 231-243 AND 506-534, AND
RP GLYCOSYLATION.
RC TISSUE=Brain;
RX PubMed=8521863; DOI=10.1111/j.1432-1033.1995.947_3.x;
RA Schulte S., Stoffel W.;
RT "UDP galactose:ceramide galactosyltransferase and glutamate/aspartate
RT transporter. Copurification, separation and characterization of the two
RT glycoproteins.";
RL Eur. J. Biochem. 233:947-953(1995).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 172-501.
RX PubMed=7527019; DOI=10.1016/0378-5955(94)90029-9;
RA Li H.S., Niedzielski A.S., Beisel K.W., Hiel H., Wenthold R.J.,
RA Morley B.J.;
RT "Identification of a glutamate/aspartate transporter in the rat cochlea.";
RL Hear. Res. 78:235-242(1994).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-512, AND IDENTIFICATION BY
RP 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:1279699, PubMed:8387171). 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 (By similarity). Plays a redundant role in the rapid removal of
CC released glutamate from the synaptic cleft, which is essential for
CC terminating the postsynaptic action of glutamate (By similarity).
CC {ECO:0000250|UniProtKB:O57321, ECO:0000250|UniProtKB:P56564,
CC ECO:0000269|PubMed:1279699, ECO:0000269|PubMed:8387171}.
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:0000250|UniProtKB:P43003};
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:P43003};
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:P43003};
CC -!- SUBUNIT: Homotrimer (By similarity). {ECO:0000250|UniProtKB:P43003}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1279699,
CC ECO:0000269|PubMed:8387171}; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=GLAST-1;
CC IsoId=P24942-1; Sequence=Displayed;
CC Name=GLAST-1A;
CC IsoId=P24942-2; Sequence=VSP_006263;
CC -!- TISSUE SPECIFICITY: Detected in brain and cerebellum (PubMed:1279699,
CC PubMed:8387171). Both isoform GLAST-1 and GLAST-1A are expressed in
CC bone and brain (PubMed:11086157). In brain isoform GLAST-1 is highly
CC enriched in the Purkinje cell layer in cerebellum (PubMed:11086157).
CC {ECO:0000269|PubMed:11086157, ECO:0000269|PubMed:1279699,
CC ECO:0000269|PubMed:8387171}.
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:8521863}.
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; X63744; CAA45276.1; -; mRNA.
DR EMBL; S59158; AAB26422.1; -; mRNA.
DR EMBL; AF265360; AAF73069.1; -; mRNA.
DR EMBL; S75687; AAB32664.1; -; mRNA.
DR PIR; S26609; S26609.
DR RefSeq; NP_001276870.1; NM_001289941.1.
DR RefSeq; NP_001276871.1; NM_001289942.1.
DR RefSeq; NP_001276872.1; NM_001289943.1.
DR RefSeq; NP_062098.1; NM_019225.2.
DR AlphaFoldDB; P24942; -.
DR SMR; P24942; -.
DR BioGRID; 248125; 3.
DR IntAct; P24942; 2.
DR MINT; P24942; -.
DR STRING; 10116.ENSRNOP00000022319; -.
DR BindingDB; P24942; -.
DR ChEMBL; CHEMBL4190; -.
DR GuidetoPHARMACOLOGY; 868; -.
DR TCDB; 2.A.23.2.1; the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.
DR iPTMnet; P24942; -.
DR PhosphoSitePlus; P24942; -.
DR SwissPalm; P24942; -.
DR PaxDb; P24942; -.
DR PRIDE; P24942; -.
DR GeneID; 29483; -.
DR KEGG; rno:29483; -.
DR CTD; 6507; -.
DR RGD; 3698; Slc1a3.
DR eggNOG; KOG3787; Eukaryota.
DR InParanoid; P24942; -.
DR PhylomeDB; P24942; -.
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:P24942; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0009925; C:basal plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
DR GO; GO:0071944; C:cell periphery; ISO:RGD.
DR GO; GO:0042995; C:cell projection; ISO:RGD.
DR GO; GO:0009986; C:cell surface; ISO: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:0098796; C:membrane protein complex; IDA:ARUK-UCL.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:ARUK-UCL.
DR GO; GO:0043025; C:neuronal cell body; IDA:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0015172; F:acidic amino acid transmembrane transporter activity; ISO:RGD.
DR GO; GO:0016597; F:amino acid binding; ISO:RGD.
DR GO; GO:0016595; F:glutamate binding; ISO:RGD.
DR GO; GO:0015501; F:glutamate:sodium symporter activity; IMP:UniProtKB.
DR GO; GO:0005314; F:high-affinity L-glutamate transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0005313; F:L-glutamate transmembrane transporter activity; IDA: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:0031223; P:auditory behavior; ISO:RGD.
DR GO; GO:0048667; P:cell morphogenesis involved in neuron differentiation; ISO:RGD.
DR GO; GO:0071314; P:cellular response to cocaine; ISO:RGD.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; ISO:RGD.
DR GO; GO:1902476; P:chloride transmembrane transport; ISS:UniProtKB.
DR GO; GO:0021545; P:cranial nerve development; ISO:RGD.
DR GO; GO:0070779; P:D-aspartate import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0009449; P:gamma-aminobutyric acid biosynthetic process; ISO:RGD.
DR GO; GO:0140009; P:L-aspartate import across plasma membrane; IMP:UniProtKB.
DR GO; GO:0051938; P:L-glutamate import; ISO:RGD.
DR GO; GO:0098712; P:L-glutamate import across plasma membrane; IMP:UniProtKB.
DR GO; GO:0015813; P:L-glutamate transmembrane transport; IDA:RGD.
DR GO; GO:0043490; P:malate-aspartate shuttle; IDA:RGD.
DR GO; GO:0050885; P:neuromuscular process controlling balance; ISO:RGD.
DR GO; GO:0006836; P:neurotransmitter transport; TAS:RGD.
DR GO; GO:0050806; P:positive regulation of synaptic transmission; ISO:RGD.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0046677; P:response to antibiotic; ISO:RGD.
DR GO; GO:0010035; P:response to inorganic substance; IDA:MGI.
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:0007605; P:sensory perception of sound; 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; Membrane; Metal-binding;
KW Phosphoprotein; Potassium; Reference proteome; Sodium; Symport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..543
FT /note="Excitatory amino acid transporter 1"
FT /id="PRO_0000202059"
FT TOPO_DOM 1..47
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 48..68
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 69..86
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 87..108
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 109..122
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 123..145
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 146..236
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 237..260
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 261..269
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 270..297
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 298..318
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 319..340
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 341..345
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 346..376
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 377..385
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 386..412
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 413..425
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 426..459
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 460..472
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 473..494
FT /note="Helical; Name=8"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 495..543
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 522..543
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 363..365
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:O59010"
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:0000250|UniProtKB:O59010"
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:0000250|UniProtKB:O59010"
FT BINDING 443..447
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 476
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 483
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:O59010"
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:22673903"
FT VAR_SEQ 62..107
FT /note="Missing (in isoform GLAST-1A)"
FT /evidence="ECO:0000305"
FT /id="VSP_006263"
FT VARIANT 302
FT /note="L -> V"
FT /evidence="ECO:0000269|PubMed:11086157"
SQ SEQUENCE 543 AA; 59697 MW; 5B01C220CA873BFD CRC64;
MTKSNGEEPR MGSRMERFQQ GVRKRTLLAK KKVQNITKED VKSYLFRNAF VLLTVSAVIV
GTILGFALRP YKMSYREVKY FSFPGELLMR MLQMLVLPLI ISSLVTGMAA LDSKASGKMG
MRAVVYYMTT TIIAVVIGII IVIIIHPGKG TKENMYREGK IVQVTAADAF LDLIRNMFPP
NLVEACFKQF KTSYEKRSFK VPIQANETLL GAVINNVSEA METLTRIREE MVPVPGSVNG
VNALGLVVFS MCFGFVIGNM KEQGQALREF FDSLNEAIMR LVAVIMWYAP LGILFLIAGK
ILEMEDMGVI GGQLAMYTVT VIVGLLIHAV IVLPLLYFLV TRKNPWVFIG GLLQALITAL
GTSSSSATLP ITFKCLEENN GVDKRITRFV LPVGATINMD GTALYEALAA IFIAQVNNFD
LNFGQIITIS ITATAASIGA AGIPQAGLVT MVIVLTSVGL PTDDITLIIA VDWFLDRLRT
TTNVLGDSLG AGIVEHLSRH ELKNRDVEMG NSVIEENEMK KPYQLIAQDN EPEKPVADSE
TKM
