EAA1_AMBTI
ID EAA1_AMBTI Reviewed; 543 AA.
AC O57321;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Excitatory amino acid transporter 1 {ECO:0000303|PubMed:9425012};
DE AltName: Full=SEAAT1 {ECO:0000303|PubMed:9425012};
DE AltName: Full=Sodium-dependent glutamate/aspartate transporter {ECO:0000303|PubMed:17008380};
DE Short=GLAST {ECO:0000303|PubMed:17008380};
GN Name=SLC1A3; Synonyms=EAAT1;
OS Ambystoma tigrinum (Eastern tiger salamander).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Caudata; Salamandroidea; Ambystomatidae; Ambystoma.
OX NCBI_TaxID=8305;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=9425012; DOI=10.1523/jneurosci.18-02-00698.1998;
RA Eliasof S., Arriza J.L., Leighton B.H., Kavanaugh M.P., Amara S.G.;
RT "Excitatory amino acid transporters of the salamander retina:
RT identification, localization, and function.";
RL J. Neurosci. 18:698-712(1998).
RN [2]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17008380; DOI=10.1113/jphysiol.2006.116830;
RA Owe S.G., Marcaggi P., Attwell D.;
RT "The ionic stoichiometry of the GLAST glutamate transporter in salamander
RT retinal glia.";
RL J. Physiol. (Lond.) 577:591-599(2006).
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:9425012, PubMed:17008380). 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:17008380). 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:P56564, ECO:0000269|PubMed:17008380,
CC ECO:0000269|PubMed:9425012}.
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. {ECO:0000250|UniProtKB:P43003}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17008380,
CC ECO:0000269|PubMed:9425012}; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Detected in retina (at protein level).
CC {ECO:0000269|PubMed:9425012}.
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, regions
CC involved in trimerization do not move. {ECO:0000250|UniProtKB:O59010}.
CC -!- SIMILARITY: Belongs to the dicarboxylate/amino acid:cation symporter
CC (DAACS) (TC 2.A.23) family. {ECO:0000305}.
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DR EMBL; AF018256; AAB88286.1; -; mRNA.
DR AlphaFoldDB; O57321; -.
DR SMR; O57321; -.
DR PRIDE; O57321; -.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0015501; F:glutamate:sodium symporter activity; ISS:UniProtKB.
DR GO; GO:0005314; F:high-affinity L-glutamate transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1902476; P:chloride transmembrane transport; ISS:UniProtKB.
DR GO; GO:0070779; P:D-aspartate import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0140009; P:L-aspartate import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0098712; P:L-glutamate import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB.
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 Amino-acid transport; Cell membrane; Glycoprotein; Membrane; Metal-binding;
KW Potassium; Sodium; Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..543
FT /note="Excitatory amino acid transporter 1"
FT /id="PRO_0000202060"
FT TOPO_DOM 1..47
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P43003"
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:0000250|UniProtKB:P43003"
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:0000250|UniProtKB:P43003"
FT TRANSMEM 123..145
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 146..237
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TRANSMEM 238..261
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 262..270
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TRANSMEM 271..298
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 299..319
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TRANSMEM 320..341
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 342..346
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT INTRAMEM 347..377
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 378..386
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TRANSMEM 387..413
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 414..426
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT INTRAMEM 427..460
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 461..473
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TRANSMEM 474..495
FT /note="Helical; Name=8"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 496..543
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT REGION 521..543
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 364..366
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 395
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 397
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 399
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 403
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 444..448
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 477
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 484
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 484
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 488
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT CARBOHYD 206
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 217
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 543 AA; 59395 MW; 6B495796FE581FFE CRC64;
MTKSNGEDPR AGSRMERFQQ GVRQRTLLAK KKVQNITKDD VKGFLKRNGF VLFTVIAVVV
GSILGFSVRS YHMTFRELKY FSFPGELLMR MLQMLVLPLI VSSLVTGMAA LDSKASGKMG
LRAVVYYMTT TVIAVFIGIV IVIIVHPGKG TKEHMHREGK IEPVTAADAF LDLIRNMFPP
NMVEACFKQF KTSYEKKIFK VTMPANETAV MTSVLNNVSE AMETLTKMRE EMIPVPGAVN
GVNALGLVVF SMCFGLVIGN MKEQGKALKD FFDSLNEAIM RLVAVIMWYA PIGILFLIAG
KIAEMEDMGV VGGQLGMYTV TVIIGLLIHA VIVLPLLYFA VTRKNPWVFI GGILQALITA
LGTSSSSATL PITFKCLEEN NKVDKRVTRF VLPVGATINM DGTALYEALA AIFIAQVNNY
DLNFGQILTI SITATAASIG AAGIPQAGLV TMVIVLTSVG LPTDDITLII AVDWFLDRLR
TTTNVLGDSL GAGIVEHLSR HELQSGDAEM GNSVIEENEM KKPYQLVSQE NELEKPIDSE
TKM
