EAA4_MOUSE
ID EAA4_MOUSE Reviewed; 561 AA.
AC O35544;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Excitatory amino acid transporter 4;
DE AltName: Full=High-affinity neuronal glutamate transporter;
DE AltName: Full=Sodium-dependent glutamate/aspartate transporter;
DE AltName: Full=Solute carrier family 1 member 6;
GN Name=Slc1a6; Synonyms=Eaat4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Cerebellum;
RX PubMed=9379843; DOI=10.1016/s0169-328x(97)00169-1;
RA Maeno-Hikichi Y., Tanaka K., Shibata T., Watanabe M., Inoue Y.,
RA Mukainaka Y., Wada K.;
RT "Structure and functional expression of the cloned mouse neuronal high-
RT affinity glutamate transporter.";
RL Brain Res. Mol. Brain Res. 48:176-180(1997).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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:9379843). Functions as a symporter that transports one amino
CC acid molecule together with two or three Na(+) ions and one proton, in
CC parallel with the counter-transport of one K(+) ion. 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(+) symport (By
CC similarity). Plays a redundant role in the rapid removal of released
CC glutamate from the synaptic cleft, which is essential for terminating
CC the postsynaptic action of glutamate (Probable).
CC {ECO:0000250|UniProtKB:O35921, ECO:0000269|PubMed:9379843,
CC ECO:0000305}.
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:P48664};
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:P48664};
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:P48664};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=40 uM for L-glutamate {ECO:0000269|PubMed:9379843};
CC -!- SUBUNIT: Homotrimer. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9379843};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Brain specific. {ECO:0000269|PubMed:9379843}.
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 -!- SIMILARITY: Belongs to the dicarboxylate/amino acid:cation symporter
CC (DAACS) (TC 2.A.23) family. SLC1A6 subfamily. {ECO:0000305}.
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DR EMBL; D83262; BAA23640.1; -; mRNA.
DR CCDS; CCDS23970.1; -.
DR RefSeq; NP_033226.1; NM_009200.3.
DR AlphaFoldDB; O35544; -.
DR SMR; O35544; -.
DR BioGRID; 203292; 1.
DR STRING; 10090.ENSMUSP00000005490; -.
DR GlyGen; O35544; 3 sites.
DR iPTMnet; O35544; -.
DR PhosphoSitePlus; O35544; -.
DR SwissPalm; O35544; -.
DR MaxQB; O35544; -.
DR PaxDb; O35544; -.
DR PRIDE; O35544; -.
DR ProteomicsDB; 275426; -.
DR Antibodypedia; 26923; 190 antibodies from 25 providers.
DR DNASU; 20513; -.
DR Ensembl; ENSMUST00000005490; ENSMUSP00000005490; ENSMUSG00000005357.
DR GeneID; 20513; -.
DR KEGG; mmu:20513; -.
DR UCSC; uc007fyg.2; mouse.
DR CTD; 6511; -.
DR MGI; MGI:1096331; Slc1a6.
DR VEuPathDB; HostDB:ENSMUSG00000005357; -.
DR eggNOG; KOG3787; Eukaryota.
DR GeneTree; ENSGT00940000159972; -.
DR HOGENOM; CLU_019375_3_2_1; -.
DR InParanoid; O35544; -.
DR OMA; AQIYGIP; -.
DR OrthoDB; 1184392at2759; -.
DR PhylomeDB; O35544; -.
DR TreeFam; TF315206; -.
DR Reactome; R-MMU-210500; Glutamate Neurotransmitter Release Cycle.
DR Reactome; R-MMU-425393; Transport of inorganic cations/anions and amino acids/oligopeptides.
DR BioGRID-ORCS; 20513; 2 hits in 70 CRISPR screens.
DR ChiTaRS; Slc1a6; mouse.
DR PRO; PR:O35544; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; O35544; protein.
DR Bgee; ENSMUSG00000005357; Expressed in cerebellar vermis and 68 other tissues.
DR ExpressionAtlas; O35544; baseline and differential.
DR Genevisible; O35544; MM.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; ISO:MGI.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0098796; C:membrane protein complex; ISO:MGI.
DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0008509; F:anion transmembrane transporter activity; ISO:MGI.
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:0015183; F:L-aspartate transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005313; F:L-glutamate transmembrane transporter activity; IMP:MGI.
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:0051649; P:establishment of localization in cell; IMP:MGI.
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:0015813; P:L-glutamate transmembrane transport; IMP:MGI.
DR GO; GO:0001504; P:neurotransmitter uptake; ISO:MGI.
DR GO; GO:0042391; P:regulation of membrane potential; IMP:MGI.
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; Chloride; Glycoprotein; Membrane;
KW Metal-binding; Phosphoprotein; Potassium; Reference proteome; Sodium;
KW Symport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..561
FT /note="Excitatory amino acid transporter 4"
FT /id="PRO_0000202071"
FT TOPO_DOM 1..52
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 53..73
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 96..116
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 130..150
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 259..282
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TRANSMEM 292..319
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TRANSMEM 341..362
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT INTRAMEM 368..398
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TRANSMEM 408..434
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT INTRAMEM 448..481
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TRANSMEM 495..516
FT /note="Helical; Name=8"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 385..387
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 416
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 418
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 420
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 424
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 465..469
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 498
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 505
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 505
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 509
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35921"
FT CARBOHYD 213
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 229
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 236
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 561 AA; 60784 MW; CCFE3FD499D4CBBB CRC64;
MSSHGNSLFL RESGAGGGCL QGLQDSLQQR ALRTRLRLQT MTREHVRRFL RRNAFILLTV
SAVIIGVSLA FALRPYQLSY RQIKYFSFPG ELLMRMLQML VLPLIVSSLV TGMASLDNKA
TGRMGMRAAV YYMVTTVIAV FIGILMVTII HPGKGSKEGL HREGRIETVP TADAFMDLVR
NMFPPNLVEA CFKQFKTQYS TRVVTRTIVR TDNGSELGAS MSPTSSVENE TSILENVTRA
LGTLQEVISF EETVPVPGSA NGINALGLVV FSVAFGLVIG GMKHKGRVLR DFFDSLNEAI
MRLVGIIIWY APVGILFLIA GKILEMEDMA VLGGQLGMYT LTVIVGLFLH AGGVLPLIYF
LVTHRNPFPF IGGMLQALIT AMGTSSSSAT LPITFRCLEE GLGVDRRITR FVLPVGATVN
MDGTALYEAL AAIFIAQVNN YELNLGQITT ISITATAASV GAAGIPQAGL VTMVIVLTSV
GLPTEDITLI IAVDWFLDRL RTMTNVLGDS IGAAVIEHLS QRELELQEAE LTLPSLGKPY
KSLMAQEKGA SRGRGGNESV M
