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Protein

Excitatory amino acid transporter 2

Gene

SLC1A2

Organism
Homo sapiens (Human)
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:7521911, PubMed:14506254, PubMed:15265858, 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). Essential for the rapid removal of released glutamate from the synaptic cleft, and for terminating the postsynaptic action of glutamate (By similarity).By similarity3 Publications

Kineticsi

  1. KM=391 µM for L-glutamate1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi393Sodium 1; via carbonyl oxygenBy similarity1
    Metal bindingi395Sodium 2; via carbonyl oxygenBy similarity1
    Metal bindingi397Sodium 1By similarity1
    Binding sitei401AspartateBy similarity1
    Binding sitei475AspartateBy similarity1
    Metal bindingi482Sodium 1; via carbonyl oxygenBy similarity1
    Binding sitei482AspartateBy similarity1
    Metal bindingi486Sodium 1By similarity1

    GO - Molecular functioni

    • amino acid transmembrane transporter activity Source: Reactome
    • glutamate:sodium symporter activity Source: UniProtKB
    • high-affinity glutamate transmembrane transporter activity Source: UniProtKB
    • L-glutamate transmembrane transporter activity Source: BHF-UCL
    • metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    Keywordsi

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

    Enzyme and pathway databases

    ReactomeiR-HSA-210455. Astrocytic Glutamate-Glutamine Uptake And Metabolism.
    R-HSA-210500. Glutamate Neurotransmitter Release Cycle.
    R-HSA-425393. Transport of inorganic cations/anions and amino acids/oligopeptides.

    Protein family/group databases

    TCDBi2.A.23.2.7. the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Excitatory amino acid transporter 2
    Alternative name(s):
    Glutamate/aspartate transporter II
    Sodium-dependent glutamate/aspartate transporter 2
    Solute carrier family 1 member 2
    Gene namesi
    Name:SLC1A2
    Synonyms:EAAT2, GLT1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 11

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000110436.11.
    HGNCiHGNC:10940. SLC1A2.

    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 – 44CytoplasmicCuratedAdd BLAST44
    Transmembranei45 – 64HelicalSequence analysisAdd BLAST20
    Topological domaini65 – 87ExtracellularCuratedAdd BLAST23
    Transmembranei88 – 108HelicalSequence analysisAdd BLAST21
    Topological domaini109 – 120CytoplasmicCuratedAdd BLAST12
    Transmembranei121 – 142HelicalSequence analysisAdd BLAST22
    Topological domaini143 – 235ExtracellularCuratedAdd BLAST93
    Transmembranei236 – 259Helical; Name=4By similarityAdd BLAST24
    Topological domaini260 – 268CytoplasmicCurated9
    Transmembranei269 – 296Helical; Name=5By similarityAdd BLAST28
    Topological domaini297 – 317ExtracellularCuratedAdd BLAST21
    Transmembranei318 – 339Helical; Name=6By similarityAdd BLAST22
    Topological domaini340 – 344CytoplasmicCurated5
    Intramembranei345 – 375Discontinuously helicalBy similarityAdd BLAST31
    Topological domaini376 – 384CytoplasmicCurated9
    Transmembranei385 – 411Helical; Name=7By similarityAdd BLAST27
    Topological domaini412 – 424ExtracellularCuratedAdd BLAST13
    Intramembranei425 – 458Discontinuously helicalBy similarityAdd BLAST34
    Topological domaini459 – 471ExtracellularCuratedAdd BLAST13
    Transmembranei472 – 493Helical; Name=8By similarityAdd BLAST22
    Topological domaini494 – 574CytoplasmicCuratedAdd BLAST81

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Epileptic encephalopathy, early infantile, 41 (EIEE41)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE41 inheritance is autosomal dominant.
    See also OMIM:617105
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_07708382G → R in EIEE41. 1 Publication1
    Natural variantiVAR_07708485L → P in EIEE41. 1 Publication1

    Keywords - Diseasei

    Disease mutation, Epilepsy

    Organism-specific databases

    DisGeNETi6506.
    MalaCardsiSLC1A2.
    MIMi617105. phenotype.
    OpenTargetsiENSG00000110436.
    PharmGKBiPA35827.

    Chemistry databases

    ChEMBLiCHEMBL4973.
    DrugBankiDB00142. L-Glutamic Acid.
    GuidetoPHARMACOLOGYi869.

    Polymorphism and mutation databases

    BioMutaiSLC1A2.
    DMDMi3041668.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002020611 – 574Excitatory amino acid transporter 2Add BLAST574

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei3PhosphoserineBy similarity1
    Modified residuei21PhosphoserineBy similarity1
    Modified residuei25PhosphoserineBy similarity1
    Lipidationi38S-palmitoyl cysteineBy similarity1
    Glycosylationi206N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi216N-linked (GlcNAc...) asparagineSequence analysis1
    Modified residuei506PhosphoserineBy similarity1
    Modified residuei521PhosphoserineBy similarity1
    Modified residuei532PhosphoserineBy similarity1
    Modified residuei534PhosphoserineBy similarity1
    Modified residuei539PhosphotyrosineBy similarity1
    Modified residuei544PhosphoserineBy similarity1
    Modified residuei560PhosphoserineBy similarity1
    Modified residuei564PhosphoserineBy similarity1

    Post-translational modificationi

    Glycosylated.1 Publication
    Palmitoylation at Cys-38 is not required for correct subcellular localization, but is important for glutamate uptake activity.By similarity

    Keywords - PTMi

    Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

    Proteomic databases

    PaxDbiP43004.
    PeptideAtlasiP43004.
    PRIDEiP43004.

    PTM databases

    iPTMnetiP43004.
    PhosphoSitePlusiP43004.
    SwissPalmiP43004.

    Miscellaneous databases

    PMAP-CutDBiP43004.

    Expressioni

    Gene expression databases

    BgeeiENSG00000110436.
    CleanExiHS_SLC1A2.
    ExpressionAtlasiP43004. baseline and differential.
    GenevisibleiP43004. HS.

    Organism-specific databases

    HPAiCAB002574.
    HPA009172.

    Interactioni

    Subunit structurei

    Homotrimer (PubMed:15265858, PubMed:15483603, PubMed:26483543). Isoform 3 can oligomerize with isoform 1 (PubMed:20688910). Interacts with AJUBA (By similarity).By similarity4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    MAPTP106364EBI-3440986,EBI-366182

    Protein-protein interaction databases

    BioGridi112397. 10 interactors.
    CORUMiP43004.
    IntActiP43004. 2 interactors.
    STRINGi9606.ENSP00000278379.

    Chemistry databases

    BindingDBiP43004.

    Structurei

    3D structure databases

    ProteinModelPortaliP43004.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni362 – 364Aspartate bindingBy similarity3
    Regioni442 – 446Aspartate 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.
    HOVERGENiHBG000080.
    InParanoidiP43004.
    KOiK05613.
    OMAiVDWFMGI.
    OrthoDBiEOG091G0UCE.
    PhylomeDBiP43004.
    TreeFamiTF315206.

    Family and domain databases

    Gene3Di1.10.3860.10. 1 hit.
    InterProiView protein in InterPro
    IPR036458. Na-dicarbo_symporter_sf.
    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.

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: P43004-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MASTEGANNM PKQVEVRMHD SHLGSEEPKH RHLGLRLCDK LGKNLLLTLT
    60 70 80 90 100
    VFGVILGAVC GGLLRLASPI HPDVVMLIAF PGDILMRMLK MLILPLIISS
    110 120 130 140 150
    LITGLSGLDA KASGRLGTRA MVYYMSTTII AAVLGVILVL AIHPGNPKLK
    160 170 180 190 200
    KQLGPGKKND EVSSLDAFLD LIRNLFPENL VQACFQQIQT VTKKVLVAPP
    210 220 230 240 250
    PDEEANATSA VVSLLNETVT EVPEETKMVI KKGLEFKDGM NVLGLIGFFI
    260 270 280 290 300
    AFGIAMGKMG DQAKLMVDFF NILNEIVMKL VIMIMWYSPL GIACLICGKI
    310 320 330 340 350
    IAIKDLEVVA RQLGMYMVTV IIGLIIHGGI FLPLIYFVVT RKNPFSFFAG
    360 370 380 390 400
    IFQAWITALG TASSAGTLPV TFRCLEENLG IDKRVTRFVL PVGATINMDG
    410 420 430 440 450
    TALYEAVAAI FIAQMNGVVL DGGQIVTVSL TATLASVGAA SIPSAGLVTM
    460 470 480 490 500
    LLILTAVGLP TEDISLLVAV DWLLDRMRTS VNVVGDSFGA GIVYHLSKSE
    510 520 530 540 550
    LDTIDSQHRV HEDIEMTKTQ SIYDDMKNHR ESNSNQCVYA AHNSVIVDEC
    560 570
    KVTLAANGKS ADCSVEEEPW KREK
    Length:574
    Mass (Da):62,104
    Last modified:July 15, 1998 - v2
    Checksum:iC8104E6727979435
    GO
    Isoform 2 (identifier: P43004-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-9: Missing.

    Show »
    Length:565
    Mass (Da):61,228
    Checksum:iA7286207F550252F
    GO
    Isoform 3 (identifier: P43004-3) [UniParc]FASTAAdd to basket
    Also known as: EEAT2b

    The sequence of this isoform differs from the canonical sequence as follows:
         553-574: TLAANGKSADCSVEEEPWKREK → HFPFMDIETCI

    Show »
    Length:563
    Mass (Da):61,008
    Checksum:iC13903644ADD1802
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti7A → T in BAG60911 (PubMed:14702039).Curated1
    Sequence conflicti19H → P in AAA50429 (PubMed:7521911).Curated1
    Sequence conflicti27E → G in CAA83532 (PubMed:7522567).Curated1
    Sequence conflicti50T → Q in AAA18900 (PubMed:8172925).Curated1
    Sequence conflicti58A → S in AAA18900 (PubMed:8172925).Curated1
    Sequence conflicti141A → G in CAA83532 (PubMed:7522567).Curated1
    Sequence conflicti155P → A in CAA83532 (PubMed:7522567).Curated1
    Sequence conflicti211V → E in AAA50429 (PubMed:7521911).Curated1
    Sequence conflicti253 – 255GIA → AIP in CAA83532 (PubMed:7522567).Curated3
    Sequence conflicti263 – 289AKLMV…MWYSP → GQADGGFLQHFERDCNEVSD HDHVVLS in CAA83532 (PubMed:7522567).CuratedAdd BLAST27
    Sequence conflicti347F → L in AAA50429 (PubMed:7521911).Curated1
    Sequence conflicti539Y → F in CAA83532 (PubMed:7522567).Curated1
    Sequence conflicti556A → G in CAA83532 (PubMed:7522567).Curated1
    Sequence conflicti563 – 565CSV → RVL in CAA83532 (PubMed:7522567).Curated3
    Sequence conflicti570W → G in CAA83532 (PubMed:7522567).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_07708382G → R in EIEE41. 1 Publication1
    Natural variantiVAR_07708485L → P in EIEE41. 1 Publication1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0371521 – 9Missing in isoform 2. 1 Publication9
    Alternative sequenceiVSP_054934553 – 574TLAAN…WKREK → HFPFMDIETCI in isoform 3. 1 PublicationAdd BLAST22

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U03505 mRNA. Translation: AAA50429.1.
    U01824 mRNA. Translation: AAA18900.1.
    Z32517 mRNA. Translation: CAA83532.1.
    D85884 mRNA. Translation: BAA28706.1.
    AY066021 mRNA. Translation: AAL57716.1.
    AK298769 mRNA. Translation: BAG60911.1.
    AL133330, AC090625 Genomic DNA. Translation: CAM28291.1.
    CH471064 Genomic DNA. Translation: EAW68143.1.
    BC132768 mRNA. Translation: AAI32769.1.
    CCDSiCCDS31459.1. [P43004-1]
    CCDS55756.1. [P43004-2]
    PIRiI37426.
    I38432.
    RefSeqiNP_001182657.1. NM_001195728.2. [P43004-2]
    NP_001239581.1. NM_001252652.1. [P43004-2]
    NP_004162.2. NM_004171.3. [P43004-1]
    UniGeneiHs.502338.
    Hs.661429.

    Genome annotation databases

    EnsembliENST00000278379; ENSP00000278379; ENSG00000110436. [P43004-1]
    ENST00000395750; ENSP00000379099; ENSG00000110436. [P43004-2]
    ENST00000395753; ENSP00000379102; ENSG00000110436. [P43004-2]
    ENST00000606205; ENSP00000476124; ENSG00000110436. [P43004-3]
    GeneIDi6506.
    KEGGihsa:6506.
    UCSCiuc001mwd.4. human. [P43004-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Entry informationi

    Entry nameiEAA2_HUMAN
    AccessioniPrimary (citable) accession number: P43004
    Secondary accession number(s): B4DQE9
    , Q14417, Q541G6, U3KQQ4
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: July 15, 1998
    Last modified: October 25, 2017
    This is version 162 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families