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Protein

Excitatory amino acid transporter 4

Gene

Slc1a6

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:14506254, PubMed:26690923). Functions as a symporter that transports one amino acid molecule together with two or three Na+ ions and one proton, in parallel with the counter-transport of one K+ ion (PubMed:14506254). Mediates Cl- flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na+ symport (PubMed:14506254). Plays a redundant role in the rapid removal of released glutamate from the synaptic cleft, which is essential for terminating the postsynaptic action of glutamate (Probable).Curated2 Publications

Kineticsi

  1. KM=328 µM for L-glutamate1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi416Sodium 1; via carbonyl oxygenBy similarity1
    Metal bindingi418Sodium 2; via carbonyl oxygenBy similarity1
    Metal bindingi420Sodium 1By similarity1
    Binding sitei424AspartateBy similarity1
    Binding sitei498AspartateBy similarity1
    Metal bindingi505Sodium 1; via carbonyl oxygenBy similarity1
    Binding sitei505AspartateBy similarity1
    Metal bindingi509Sodium 1By similarity1

    GO - Molecular functioni

    • anion transmembrane transporter activity Source: RGD
    • L-glutamate transmembrane transporter activity Source: RGD
    • symporter activity Source: UniProtKB-KW

    Keywordsi

    Biological processAmino-acid transport, Symport, Transport
    LigandChloride, Metal-binding, Potassium, Sodium

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Excitatory amino acid transporter 4
    Alternative name(s):
    High-affinity neuronal glutamate transporter
    Sodium-dependent glutamate/aspartate transporter
    Solute carrier family 1 member 6
    Gene namesi
    Name:Slc1a6
    Synonyms:Eaat4
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
    Proteomesi
    • UP000002494 Componenti: Unplaced

    Organism-specific databases

    RGDi620340. Slc1a6.

    Subcellular locationi

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 52CytoplasmicSequence analysisAdd BLAST52
    Transmembranei53 – 73HelicalSequence analysisAdd BLAST21
    Transmembranei96 – 116HelicalSequence analysisAdd BLAST21
    Transmembranei130 – 150HelicalSequence analysisAdd BLAST21
    Transmembranei259 – 282Helical; Name=4By similarityAdd BLAST24
    Transmembranei292 – 319Helical; Name=5By similarityAdd BLAST28
    Transmembranei341 – 362Helical; Name=6By similarityAdd BLAST22
    Intramembranei368 – 398Discontinuously helicalBy similarityAdd BLAST31
    Transmembranei408 – 434Helical; Name=7By similarityAdd BLAST27
    Intramembranei448 – 481Discontinuously helicalBy similarityAdd BLAST34
    Transmembranei495 – 516Helical; Name=8By similarityAdd BLAST22

    GO - Cellular componenti

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Chemistry databases

    GuidetoPHARMACOLOGYi871.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002020721 – 561Excitatory amino acid transporter 4Add BLAST561

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2PhosphoserineCombined sources1
    Glycosylationi213N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi229N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi236N-linked (GlcNAc...) asparagineSequence analysis1

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiO35921.
    PRIDEiO35921.

    PTM databases

    iPTMnetiO35921.
    PhosphoSitePlusiO35921.

    Interactioni

    Subunit structurei

    Homotrimer.Curated

    Protein-protein interaction databases

    BioGridi249878. 1 interactor.
    STRINGi10116.ENSRNOP00000009931.

    Structurei

    3D structure databases

    ProteinModelPortaliO35921.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni385 – 387Aspartate bindingBy similarity3
    Regioni465 – 469Aspartate bindingBy similarity5

    Domaini

    Contains eight transmembrane regions plus two helical hairpins that dip into the membrane. These helical hairpin structures play an important role in the transport process. The first enters the membrane from the cytoplasmic side, the second one from the extracellular side. During the transport cycle, the regions involved in amino acid transport, and especially the helical hairpins, move vertically by about 15-18 Angstroms, alternating between exposure to the aqueous phase and reinsertion in the lipid bilayer. In contrast, the regions involved in trimerization do not move.By similarity

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG3787. Eukaryota.
    COG1301. LUCA.
    HOGENOMiHOG000208776.
    HOVERGENiHBG000080.
    InParanoidiO35921.
    KOiK05617.
    PhylomeDBiO35921.

    Family and domain databases

    Gene3Di1.10.3860.10. 1 hit.
    InterProiView protein in InterPro
    IPR001991. Na-dicarboxylate_symporter.
    IPR018107. Na-dicarboxylate_symporter_CS.
    PfamiView protein in Pfam
    PF00375. SDF. 1 hit.
    PRINTSiPR00173. EDTRNSPORT.
    SUPFAMiSSF118215. SSF118215. 2 hits.
    PROSITEiView protein in PROSITE
    PS00713. NA_DICARBOXYL_SYMP_1. 1 hit.
    PS00714. NA_DICARBOXYL_SYMP_2. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    O35921-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSSHGNSLFL RESGAGGGCL QGLQDSLQQR ALRTRLRLQT MTREHVRRFL
    60 70 80 90 100
    RRNAFILLTV SAVIIGVSLA FALRPYQLTY RQIKYFSFPG ELLMRMLQML
    110 120 130 140 150
    VLPLIVSSRV TGMASLDNKA TGRMGMRAAV YYMVTTVIAV FIGILMVTII
    160 170 180 190 200
    HPGKGSKEGL HREGRIETVP TADAFMDLVR NMFPPNLVEA CFKQFKTQYS
    210 220 230 240 250
    TRVVTRTIVR TDNGSELGAS ISPPSSAENE TSILENVTRA LGTLQEVISF
    260 270 280 290 300
    EETVPVPGSA NGINALGLVV FSVAFGLVIG GMKHKGRVLR DFFDSLNEAI
    310 320 330 340 350
    MRLVGIIIWY APVGILFLIA GKILEMEDMA VLGGQLGMYT LTVIVGLFLH
    360 370 380 390 400
    AGGVLPLIYF LVTHRNPFPF IGGILQALIT AMGTSSSSAT LPITFRCLEE
    410 420 430 440 450
    GLGVDRRITR FVLPVGATVN MDGTALYEAL AAIFIAQVNN YELNLGQITT
    460 470 480 490 500
    ISITATAASV GAAGIPQAGL VTMVIVLTSV GLPTEDITLI IAVDWFLDRL
    510 520 530 540 550
    RTMTNVLGDS IGAAVIEHLS QRELELQEAE LTLPSLGKPY KSLMAQAKGA
    560
    SRGRGGNESV M
    Length:561
    Mass (Da):60,715
    Last modified:January 1, 1998 - v1
    Checksum:iAAF1298EE6AA8359
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti119K → R in AAB40997 (Ref. 2) Curated1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U89608 mRNA. Translation: AAB72086.1.
    U80915 mRNA. Translation: AAB40997.1.
    RefSeqiNP_114454.1. NM_032065.1.
    UniGeneiRn.10827.

    Genome annotation databases

    GeneIDi84012.
    KEGGirno:84012.
    UCSCiRGD:620340. rat.

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

    Entry informationi

    Entry nameiEAA4_RAT
    AccessioniPrimary (citable) accession number: O35921
    Secondary accession number(s): P97683
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: January 1, 1998
    Last modified: July 5, 2017
    This is version 102 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families