EAA4_CANLF
ID EAA4_CANLF Reviewed; 564 AA.
AC Q9N1R2;
DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Excitatory amino acid transporter 4;
DE AltName: Full=Sodium-dependent glutamate/aspartate transporter;
DE AltName: Full=Solute carrier family 1 member 6;
GN Name=SLC1A6; Synonyms=EAAT4;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10692470; DOI=10.1074/jbc.275.9.6620;
RA Sato K., Inaba M., Suwa Y., Matsuu A., Hikasa Y., Ono K., Kagota K.;
RT "Inherited defects of sodium-dependent glutamate transport mediated by
RT glutamate/aspartate transporter in canine red cells due to a decreased
RT level of transporter protein expression.";
RL J. Biol. Chem. 275:6620-6627(2000).
CC -!- FUNCTION: Sodium-dependent, high-affinity amino acid transporter that
CC mediates the uptake of L-glutamate and also L-aspartate and D-
CC aspartate. Functions as a symporter that transports one amino acid
CC 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.
CC Plays a redundant role in the rapid removal of released glutamate from
CC the synaptic cleft, which is essential for terminating the postsynaptic
CC action of glutamate. {ECO:0000250|UniProtKB:O35921}.
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 -!- SUBUNIT: Homotrimer. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O35921};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:O35921}.
CC -!- TISSUE SPECIFICITY: Detected in brain, cerebellum and hippocampus.
CC {ECO:0000269|PubMed:10692470}.
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; AF167077; AAF14543.2; -; mRNA.
DR RefSeq; NP_001003137.1; NM_001003137.1.
DR AlphaFoldDB; Q9N1R2; -.
DR SMR; Q9N1R2; -.
DR STRING; 9612.ENSCAFP00000023841; -.
DR PaxDb; Q9N1R2; -.
DR GeneID; 403749; -.
DR CTD; 6511; -.
DR eggNOG; KOG3787; Eukaryota.
DR InParanoid; Q9N1R2; -.
DR OrthoDB; 1184392at2759; -.
DR Proteomes; UP000002254; Unplaced.
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:0015183; F:L-aspartate transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005313; F:L-glutamate transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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 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 2: Evidence at transcript 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..564
FT /note="Excitatory amino acid transporter 4"
FT /id="PRO_0000202069"
FT TOPO_DOM 1..55
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 56..76
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 99..119
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 133..153
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..285
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TRANSMEM 295..322
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TRANSMEM 344..365
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT INTRAMEM 371..401
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TRANSMEM 411..437
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT INTRAMEM 451..484
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TRANSMEM 498..519
FT /note="Helical; Name=8"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 388..390
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 419
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 421
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 423
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 427
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 468..472
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 501
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 508
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT BINDING 508
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O59010"
FT BINDING 512
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 216
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 232
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 239
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 564 AA; 61466 MW; 6682E9F6A49021CD CRC64;
MSSHGNSLFL RESGQRLGRV GWLQRLQESL QQRALRTRLR LQTMTREHVL RFLRRNAFIL
LTVSAVVIGV SLAFALRPYQ LTYRQIKYFS FPGELLMRML QMLVLPLIVS SLVTGMASLD
NKATGRMGMR AAVYYMVTTV IAVFIGILMV TIIHPGKGSK EGLHREGRIE TIPTADAFMD
LVRNMFPPNL VEACFKQFKT QYSTRLVTRT IVRTENGSEL GTSMPPPSSM DNGTSLLENV
TWALGTLQEV LSFEETVPVP GSANGINALG LVVFSVAFGL VIGGVKHKGR VLRDFFDSLN
EAIMRMVGII IWYAPVGILF LIAGKILEME DMAVLGGQLG MYTLTVIVGL FLHAGGVLPL
IYFLITHRNP FPFIGGVLQA LITAMGTSSS SATLPITFRC LEEGLGVDRR ITRFVLPVGA
TVNMDGTALY EALAAIFIAQ VNNYELNLGQ ITTISITATA ASVGAAGIPQ AGLVTMVIVL
TSVGLPTEDI TLIIAVDWFL DRLRTMTNVL GDSIGAAVIE HLSQRELELQ EAELTLPSLG
KPYKPLMAQE KGASRGRGGN ESAM
