EAA3_BOVIN
ID EAA3_BOVIN Reviewed; 524 AA.
AC Q95135;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Excitatory amino acid transporter 3;
DE AltName: Full=Excitatory amino-acid carrier 1;
DE AltName: Full=Renal high affinity glutamate transporter EAAC1;
DE AltName: Full=Sodium-dependent glutamate/aspartate transporter 3;
DE AltName: Full=Solute carrier family 1 member 1;
GN Name=SLC1A1; Synonyms=EAAC1, EAAT3;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8647808; DOI=10.1074/jbc.271.21.12159;
RA Nicholson B., McGivan J.D.;
RT "Induction of high affinity glutamate transport activity by amino acid
RT deprivation in renal epithelial cells does not involve an increase in the
RT amount of transporter protein.";
RL J. Biol. Chem. 271:12159-12164(1996).
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. Can also transport L-cysteine (By similarity). Functions as
CC a symporter that transports one amino acid molecule together with two
CC or three Na(+) ions and one proton, in parallel with the counter-
CC transport of one K(+) ion. Mediates Cl(-) flux that is not coupled to
CC amino acid transport; this avoids the accumulation of negative charges
CC due to aspartate and Na(+) symport (By similarity). Plays an important
CC role in L-glutamate and L-aspartate reabsorption in renal tubuli. Plays
CC a redundant role in the rapid removal of released glutamate from the
CC synaptic cleft, which is essential for terminating the postsynaptic
CC action of glutamate (By similarity). Contributes to glutathione
CC biosynthesis and protection against oxidative stress via its role in L-
CC glutamate and L-cysteine transport. Negatively regulated by ARL6IP5 (By
CC similarity). {ECO:0000250|UniProtKB:P43005,
CC ECO:0000250|UniProtKB:P51906}.
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: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:P43005};
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 -!- SUBUNIT: Homotrimer. Interacts with ARL6IP5. Interacts with RTN2 (via
CC N-terminus); the interaction promotes cell surface expression of
CC SLC1A1. Interacts with SORCS2; this interaction is important for normal
CC expression at the cell membrane. {ECO:0000250|UniProtKB:P51906}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P51906};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P43003}. Apical cell
CC membrane {ECO:0000250|UniProtKB:P43005}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P43003}. Synapse, synaptosome
CC {ECO:0000250|UniProtKB:P51906}. Early endosome membrane
CC {ECO:0000250|UniProtKB:P51906}. Late endosome membrane
CC {ECO:0000250|UniProtKB:P51906}. Recycling endosome membrane
CC {ECO:0000250|UniProtKB:P51906}.
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. SLC1A1 subfamily. {ECO:0000305}.
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DR EMBL; U72534; AAB16815.1; -; mRNA.
DR PIR; S39017; S39017.
DR RefSeq; NP_777024.1; NM_174599.2.
DR AlphaFoldDB; Q95135; -.
DR SMR; Q95135; -.
DR STRING; 9913.ENSBTAP00000025456; -.
DR PaxDb; Q95135; -.
DR PRIDE; Q95135; -.
DR GeneID; 282353; -.
DR KEGG; bta:282353; -.
DR CTD; 6505; -.
DR eggNOG; KOG3787; Eukaryota.
DR InParanoid; Q95135; -.
DR OrthoDB; 1184392at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0071944; C:cell periphery; IDA:ARUK-UCL.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0015108; F:chloride transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0033229; F:cysteine transmembrane transporter activity; 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:0005313; F:L-glutamate transmembrane transporter activity; ISS:UniProtKB.
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:1902476; P:chloride transmembrane transport; ISS:UniProtKB.
DR GO; GO:0042883; P:cysteine transport; ISS:UniProtKB.
DR GO; GO:0140009; P:L-aspartate import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0070778; P:L-aspartate transmembrane transport; IGI:ARUK-UCL.
DR GO; GO:0098712; P:L-glutamate import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0015813; P:L-glutamate transmembrane transport; IGI:ARUK-UCL.
DR GO; GO:0070633; P:transepithelial transport; IGI:ARUK-UCL.
DR GO; GO:0150104; P:transport across blood-brain barrier; IGI:ARUK-UCL.
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; Endosome; Glycoprotein;
KW Membrane; Metal-binding; Phosphoprotein; Potassium; Reference proteome;
KW Sodium; Symport; Synapse; Synaptosome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..524
FT /note="Excitatory amino acid transporter 3"
FT /id="PRO_0000202064"
FT TOPO_DOM 1..18
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 19..38
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 39..61
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 62..82
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 83..93
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 94..114
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 115..205
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 206..229
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 230..238
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 239..266
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 267..286
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 287..308
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 309..313
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 314..344
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 345..353
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 354..380
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 381..393
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 394..427
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 428..440
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 441..462
FT /note="Helical; Name=8"
FT /evidence="ECO:0000250|UniProtKB:P43003"
FT TOPO_DOM 463..524
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT BINDING 98
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 101
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 102
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 331
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 333
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 362
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 364
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 366
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 368
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 370
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 405
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 406
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 408
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 411
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 447
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 448
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 451
FT /ligand="L-aspartate"
FT /ligand_id="ChEBI:CHEBI:29991"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 451
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT BINDING 455
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P43005"
FT MOD_RES 517
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51906"
FT MOD_RES 522
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51906"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 524 AA; 57297 MW; 920256A70A302128 CRC64;
MGKPARKGCD WKRFLRNNWL LLSTVVAVVL GIVIGVLVRE YSKLSNLEKF YFSFPGEILM
RMLKLVILPL IVSSMITGVA TLDSNVSGKI GLRAVVYYFC TTLIAVILGI VLVVSIKPGV
TQKVNEIDRT GNTPEVSTVD AMLDLIRNMF PENLVQACFQ QYKTTREEVE LSEEPGTNST
EATVTAIMTT AISKNKTKEY KVVGMYSDGI NVLGLIVFCL VLGIVIGRKW EKGQILVDFF
NALSDATMKI VQIIMCYMPI GILFLIAGKI IEVEDWEIFR KLGLYMATVL SGLAIHSIVI
LPLIYFIIVR KNPFQFAMGM AQALLTALMI SSSSATLPVT FRCAEEKNRV DKRITRFVLP
VGATINMDGT ALYEAVAAVF IAQLNDLDLS VGQIITISVT ATAASIGAAG VPQPGLVTMV
IVLSAVGLPA EDVTLIIAVD WLLDRFRTMV NVLGDAFGTG IVEKLSKKEL EQMDVSSEVN
IVNPFTLEST ALDNEDSDTK KSYVNGGFAV DKSDTISFTQ TSQF
