EAA3_RABIT
ID EAA3_RABIT Reviewed; 524 AA.
AC P31597;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Excitatory amino acid transporter 3;
DE AltName: Full=Excitatory amino-acid carrier 1 {ECO:0000303|PubMed:1280334};
DE AltName: Full=Sodium-dependent glutamate/aspartate transporter 3;
DE AltName: Full=Solute carrier family 1 member 1;
GN Name=SLC1A1; Synonyms=EAAC1 {ECO:0000303|PubMed:1280334}, EAAT3;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Intestine;
RX PubMed=1280334; DOI=10.1038/360467a0;
RA Kanai Y., Hediger M.A.;
RT "Primary structure and functional characterization of a high-affinity
RT glutamate transporter.";
RL Nature 360:467-471(1992).
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:1280334). Can also transport L-cysteine (By similarity).
CC Functions as a symporter that transports one amino acid molecule
CC together with two or three Na(+) ions and one proton, in parallel with
CC the counter-transport of one K(+) ion (PubMed:1280334). 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 an important role in L-glutamate and L-aspartate reabsorption in
CC renal tubuli (By similarity). Plays a redundant role in the rapid
CC removal of released glutamate from the synaptic cleft, which is
CC essential for terminating the postsynaptic action of glutamate (By
CC similarity). Contributes to glutathione biosynthesis and protection
CC against oxidative stress via its role in L-glutamate and L-cysteine
CC transport (By similarity). Negatively regulated by ARL6IP5 (By
CC similarity). {ECO:0000250|UniProtKB:P43005,
CC ECO:0000250|UniProtKB:P51906, ECO:0000269|PubMed:1280334}.
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=12 uM for L-glutamate {ECO:0000269|PubMed:1280334};
CC KM=6.5 uM for L-aspartate {ECO:0000269|PubMed:1280334};
CC KM=7.5 uM for D-aspartate {ECO:0000269|PubMed:1280334};
CC -!- SUBUNIT: Homotrimer (Probable). Interacts with ARL6IP5. Interacts with
CC RTN2 (via N-terminus); the interaction promotes cell surface expression
CC of SLC1A1. Interacts with SORCS2; this interaction is important for
CC normal expression at the cell membrane (By similarity).
CC {ECO:0000250|UniProtKB:P51906, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1280334};
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 -!- TISSUE SPECIFICITY: Brain, but also small intestine, kidney, liver and
CC heart. {ECO:0000269|PubMed:1280334}.
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 -!- MISCELLANEOUS: Transport does not depend on chloride.
CC {ECO:0000269|PubMed:1280334}.
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; L12411; AAA31257.1; -; mRNA.
DR PIR; S28902; S28902.
DR RefSeq; NP_001075718.1; NM_001082249.1.
DR AlphaFoldDB; P31597; -.
DR SMR; P31597; -.
DR STRING; 9986.ENSOCUP00000022489; -.
DR GeneID; 100009070; -.
DR KEGG; ocu:100009070; -.
DR CTD; 6505; -.
DR eggNOG; KOG3787; Eukaryota.
DR InParanoid; P31597; -.
DR OrthoDB; 1184392at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IMP: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; IDA:UniProtKB.
DR GO; GO:0005314; F:high-affinity L-glutamate transmembrane transporter activity; IDA: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:1902476; P:chloride transmembrane transport; ISS:UniProtKB.
DR GO; GO:0042883; P:cysteine transport; ISS:UniProtKB.
DR GO; GO:0070779; P:D-aspartate import across plasma membrane; IDA:UniProtKB.
DR GO; GO:0140009; P:L-aspartate import across plasma membrane; IDA:UniProtKB.
DR GO; GO:0098712; P:L-glutamate import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0015813; P:L-glutamate 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; 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_0000202068"
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 43
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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; 56939 MW; F4F483777EFE62D5 CRC64;
MGKPARKGCD SKRFLKNNWL LLSTVVAVVL GIVIGVLVRE YSNLSTLDKF YFAFPGEILM
RMLKLVILPL IVSSMITGVA ALDSNVSGKI GLRAVLYYFC TTIIAVILGI VLVVSIKPGV
TQKVDEIDRT GSTPEVSTVD AMLDLIRNMF PENLVQACFQ QYKTTREEVT ASDDTGKNGT
EESVTAVMTT AVSENRTKEY RVVGLYSDGI NVLGLIVFCL VFGLVIGKMG EKGQILVDFF
NALSDATMKI VQIIMCYMPL GILFLIAGKI IEVEDWEIFR KLGLYMVTVL SGLAIHSIVI
LPLIYFIVVR KNPFRFAMGM TQALLTALMI SSSSATLPVT FRCAEEKNRV DKRITRFVLP
VGATINMDGT ALYEAVAAVF IAQLNDMDLS IGQIITISVT ATAASIGAAG VPQAGLVTMV
IVLSAVGLPA EDVTLIIAVD WLLDRFRTVV NVLGDAFGTG IVEKLSKKEL EQMDVSSEVN
IVNPFALESA TLDNEDSDTK KSYINGGFAV DKSDTISFTQ TSQF
