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Protein

Excitatory amino acid transporter 4

Gene

Slc1a6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 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:9379843). 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. Mediates Cl- flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na+ symport (By similarity). 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).By similarityCurated1 Publication

Kineticsi

  1. KM=40 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

    GO - Biological processi

    • L-glutamate import across plasma membrane Source: UniProtKB
    • L-glutamate transport Source: MGI
    • regulation of membrane potential Source: MGI

    Keywordsi

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

    Enzyme and pathway databases

    ReactomeiR-MMU-210500. Glutamate Neurotransmitter Release Cycle.
    R-MMU-425393. Transport of inorganic cations/anions and amino acids/oligopeptides.

    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
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 10

    Organism-specific databases

    MGIiMGI:1096331. Slc1a6.

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    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

    Keywords - Cellular componenti

    Cell membrane, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002020711 – 561Excitatory amino acid transporter 4Add BLAST561

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2PhosphoserineBy similarity1
    Glycosylationi213N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi229N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi236N-linked (GlcNAc...) asparagineSequence analysis1

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    MaxQBiO35544.
    PaxDbiO35544.
    PRIDEiO35544.

    PTM databases

    iPTMnetiO35544.
    PhosphoSitePlusiO35544.
    SwissPalmiO35544.

    Expressioni

    Tissue specificityi

    Brain specific.1 Publication

    Gene expression databases

    BgeeiENSMUSG00000005357.
    ExpressionAtlasiO35544. baseline and differential.
    GenevisibleiO35544. MM.

    Interactioni

    Subunit structurei

    Homotrimer.Curated

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000005490.

    Structurei

    3D structure databases

    ProteinModelPortaliO35544.
    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.
    GeneTreeiENSGT00760000119117.
    HOGENOMiHOG000208776.
    HOVERGENiHBG000080.
    InParanoidiO35544.
    KOiK05617.
    OMAiEKAWWIS.
    OrthoDBiEOG091G0UCE.
    PhylomeDBiO35544.
    TreeFamiTF315206.

    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.

    O35544-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSSHGNSLFL RESGAGGGCL QGLQDSLQQR ALRTRLRLQT MTREHVRRFL
    60 70 80 90 100
    RRNAFILLTV SAVIIGVSLA FALRPYQLSY RQIKYFSFPG ELLMRMLQML
    110 120 130 140 150
    VLPLIVSSLV TGMASLDNKA TGRMGMRAAV YYMVTTVIAV FIGILMVTII
    160 170 180 190 200
    HPGKGSKEGL HREGRIETVP TADAFMDLVR NMFPPNLVEA CFKQFKTQYS
    210 220 230 240 250
    TRVVTRTIVR TDNGSELGAS MSPTSSVENE 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 IGGMLQALIT 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 KSLMAQEKGA
    560
    SRGRGGNESV M
    Length:561
    Mass (Da):60,784
    Last modified:January 1, 1998 - v1
    Checksum:iCCFE3FD499D4CBBB
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    D83262 mRNA. Translation: BAA23640.1.
    CCDSiCCDS23970.1.
    RefSeqiNP_033226.1. NM_009200.3.
    UniGeneiMm.6257.

    Genome annotation databases

    EnsembliENSMUST00000005490; ENSMUSP00000005490; ENSMUSG00000005357.
    GeneIDi20513.
    KEGGimmu:20513.
    UCSCiuc007fyg.2. mouse.

    Similar proteinsi

    Entry informationi

    Entry nameiEAA4_MOUSE
    AccessioniPrimary (citable) accession number: O35544
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: January 1, 1998
    Last modified: August 30, 2017
    This is version 128 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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families