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Protein

Excitatory amino acid transporter 1

Gene

Slc1a3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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:7903437, PubMed:28032905). 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 (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 (PubMed:15363892, PubMed:15390100,PubMed:16880397).By similarity5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi394Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi396Sodium 2; via carbonyl oxygenBy similarity1
Metal bindingi398Sodium 1By similarity1
Binding sitei402AspartateBy similarity1
Binding sitei476AspartateBy similarity1
Metal bindingi483Sodium 1; via carbonyl oxygenBy similarity1
Binding sitei483AspartateBy similarity1
Metal bindingi487Sodium 1By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-210455 Astrocytic Glutamate-Glutamine Uptake And Metabolism
R-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 1
Alternative name(s):
Glial high affinity glutamate transporter
High-affinity neuronal glutamate transporter
Short name:
GluT-11 Publication
Sodium-dependent glutamate/aspartate transporter 1
Short name:
GLAST-1
Solute carrier family 1 member 3
Gene namesi
Name:Slc1a3
Synonyms:Eaat1, Gmt1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:99917 Slc1a3

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 – 47CytoplasmicBy similarityAdd BLAST47
Transmembranei48 – 68Helical; Name=1By similarityAdd BLAST21
Topological domaini69 – 86ExtracellularBy similarityAdd BLAST18
Transmembranei87 – 108Helical; Name=2By similarityAdd BLAST22
Topological domaini109 – 122CytoplasmicBy similarityAdd BLAST14
Transmembranei123 – 145Helical; Name=3By similarityAdd BLAST23
Topological domaini146 – 236ExtracellularBy similarityAdd BLAST91
Transmembranei237 – 260Helical; Name=4By similarityAdd BLAST24
Topological domaini261 – 269CytoplasmicBy similarity9
Transmembranei270 – 297Helical; Name=5By similarityAdd BLAST28
Topological domaini298 – 318ExtracellularBy similarityAdd BLAST21
Transmembranei319 – 340Helical; Name=6By similarityAdd BLAST22
Topological domaini341 – 345CytoplasmicBy similarity5
Intramembranei346 – 376Discontinuously helicalBy similarityAdd BLAST31
Topological domaini377 – 385CytoplasmicBy similarity9
Transmembranei386 – 412Helical; Name=7By similarityAdd BLAST27
Topological domaini413 – 425ExtracellularBy similarityAdd BLAST13
Intramembranei426 – 459Discontinuously helicalBy similarityAdd BLAST34
Topological domaini460 – 472ExtracellularBy similarityAdd BLAST13
Transmembranei473 – 494Helical; Name=8By similarityAdd BLAST22
Topological domaini495 – 543CytoplasmicBy similarityAdd BLAST49

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

No visible phenotype (PubMed:15363892, PubMed:15390100). Mutant mice display normal locomotion, motor coordination and learning, and globally normal glutamate uptake in brain vesicle preparations (PubMed:15363892). The decay time of glutamate receptor mediated excitatory postsynaptic currents (EPSCs) in cerebellar Purkinje is slightly increased (PubMed:15363892). The decreased rate of glutamate uptake in retina Mueller cells from mutant mice suggests that Slc1a3 accounts for about half of the glutamate uptake activity in wild-type cells (PubMed:15390100). Mice deficient in both Slc1a2 and Slc1a3 die at about 17 dpc (PubMed:16880397).3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002020581 – 543Excitatory amino acid transporter 1Add BLAST543

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi206N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi216N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei512PhosphoserineCombined sources1

Post-translational modificationi

Glycosylated.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP56564
PeptideAtlasiP56564
PRIDEiP56564

PTM databases

iPTMnetiP56564
PhosphoSitePlusiP56564
SwissPalmiP56564

Expressioni

Tissue specificityi

Detected in brain, in Bergmann glia arborising into the molecular layer of the cerebellum (at protein level) (PubMed:15363892). Localized in brain and is highly enriched in the Purkinje cell layer in cerebellum. Intermediate level in lung, low level in spleen, skeletal muscle and testis.1 Publication

Gene expression databases

BgeeiENSMUSG00000005360 Expressed in 270 organ(s), highest expression level in cerebellum lobe
ExpressionAtlasiP56564 baseline and differential
GenevisibleiP56564 MM

Interactioni

Subunit structurei

Homotrimer.By similarity

Protein-protein interaction databases

BioGridi203291, 6 interactors
IntActiP56564, 3 interactors
STRINGi10090.ENSMUSP00000005493

Structurei

3D structure databases

ProteinModelPortaliP56564
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni363 – 365Aspartate bindingBy similarity3
Regioni443 – 447Aspartate bindingBy similarity5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi363 – 366Poly-Ser4

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
InParanoidiP56564
KOiK05614
OMAiTFAFSSR
OrthoDBiEOG091G0UCE
PhylomeDBiP56564
TreeFamiTF315206

Family and domain databases

Gene3Di1.10.3860.10, 2 hits
InterProiView protein in InterPro
IPR001991 Na-dicarboxylate_symporter
IPR018107 Na-dicarboxylate_symporter_CS
IPR036458 Na:dicarbo_symporter_sf
PfamiView protein in Pfam
PF00375 SDF, 1 hit
SUPFAMiSSF118215 SSF118215, 1 hit
PROSITEiView protein in PROSITE
PS00713 NA_DICARBOXYL_SYMP_1, 1 hit
PS00714 NA_DICARBOXYL_SYMP_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

P56564-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTKSNGEEPR MGGRMERLQQ GVRKRTLLAK KKVQSLTKED VKSYLFRNAF
60 70 80 90 100
VLLTVTAVIV GTILGFALRP YKMSYREVKY FSFPGELLMR MLQMLVLPLI
110 120 130 140 150
ISSLVTGMAA LDSKASGKMG MRAVVYYMTT TIIAVVIGII IVIIIHPGKG
160 170 180 190 200
TKENMYREGK IVQVTAADAF LDLIRNMFPP NLVEACFKQF KTSYEKRSFK
210 220 230 240 250
VPIQSNETLL GAVINNVSEA METLTRIREE MVPVPGSVNG VNALGLVVFS
260 270 280 290 300
MCFGFVIGNM KEQGQALREF FDSLNEAIMR LVAVIMWYAP LGILFLIAGK
310 320 330 340 350
IVEMEDMGVI GGQLAMYTVT VIVGLLIHAV IVLPLLYFLV TRKNPWVFIG
360 370 380 390 400
GLLQALITAL GTSSSSATLP ITFKCLEENN GVDKRITRFV LPVGATINMD
410 420 430 440 450
GTALYEALAA IFIAQVNNFD LNFGQIITIS ITATAASIGA AGIPQAGLVT
460 470 480 490 500
MVIVLTSVGL PTDDITLIIA VDWFLDRLRT TTNVLGDSLG AGIVEHLSRH
510 520 530 540
ELKNRDVEMG NSVIEENEMK KPYQLIAQDN EPEKPVADSE TKM
Length:543
Mass (Da):59,622
Last modified:March 5, 2002 - v2
Checksum:iE0B24CBA1D5B086D
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D3YY51D3YY51_MOUSE
Amino acid transporter
Slc1a3
129Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF330257 mRNA Translation: AAK01708.1
BC058711 mRNA Translation: AAH58711.1
BC066154 mRNA Translation: AAH66154.1
CCDSiCCDS27373.1
RefSeqiNP_683740.1, NM_148938.3
UniGeneiMm.204834

Genome annotation databases

EnsembliENSMUST00000005493; ENSMUSP00000005493; ENSMUSG00000005360
GeneIDi20512
KEGGimmu:20512
UCSCiuc007vex.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF330257 mRNA Translation: AAK01708.1
BC058711 mRNA Translation: AAH58711.1
BC066154 mRNA Translation: AAH66154.1
CCDSiCCDS27373.1
RefSeqiNP_683740.1, NM_148938.3
UniGeneiMm.204834

3D structure databases

ProteinModelPortaliP56564
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203291, 6 interactors
IntActiP56564, 3 interactors
STRINGi10090.ENSMUSP00000005493

PTM databases

iPTMnetiP56564
PhosphoSitePlusiP56564
SwissPalmiP56564

Proteomic databases

PaxDbiP56564
PeptideAtlasiP56564
PRIDEiP56564

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000005493; ENSMUSP00000005493; ENSMUSG00000005360
GeneIDi20512
KEGGimmu:20512
UCSCiuc007vex.1 mouse

Organism-specific databases

CTDi6507
MGIiMGI:99917 Slc1a3

Phylogenomic databases

eggNOGiKOG3787 Eukaryota
COG1301 LUCA
GeneTreeiENSGT00760000119117
HOGENOMiHOG000208776
HOVERGENiHBG000080
InParanoidiP56564
KOiK05614
OMAiTFAFSSR
OrthoDBiEOG091G0UCE
PhylomeDBiP56564
TreeFamiTF315206

Enzyme and pathway databases

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

Miscellaneous databases

PROiPR:P56564
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000005360 Expressed in 270 organ(s), highest expression level in cerebellum lobe
ExpressionAtlasiP56564 baseline and differential
GenevisibleiP56564 MM

Family and domain databases

Gene3Di1.10.3860.10, 2 hits
InterProiView protein in InterPro
IPR001991 Na-dicarboxylate_symporter
IPR018107 Na-dicarboxylate_symporter_CS
IPR036458 Na:dicarbo_symporter_sf
PfamiView protein in Pfam
PF00375 SDF, 1 hit
SUPFAMiSSF118215 SSF118215, 1 hit
PROSITEiView protein in PROSITE
PS00713 NA_DICARBOXYL_SYMP_1, 1 hit
PS00714 NA_DICARBOXYL_SYMP_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiEAA1_MOUSE
AccessioniPrimary (citable) accession number: P56564
Secondary accession number(s): Q99P53
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: March 5, 2002
Last modified: November 7, 2018
This is version 157 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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