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Protein

Excitatory amino acid transporter 2

Gene

Slc1a2

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:7698742, PubMed:7557442, PubMed:9373176). 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). Essential for the rapid removal of released glutamate from the synaptic cleft, and for terminating the postsynaptic action of glutamate (PubMed:9180080).By similarity4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi392Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi394Sodium 2; via carbonyl oxygenBy similarity1
Metal bindingi396Sodium 1By similarity1
Binding sitei400AspartateBy similarity1
Binding sitei474AspartateBy similarity1
Metal bindingi481Sodium 1; via carbonyl oxygenBy similarity1
Binding sitei481AspartateBy similarity1
Metal bindingi485Sodium 1By similarity1

GO - Molecular functioni

  • anion transmembrane transporter activity Source: MGI
  • glutamate:sodium symporter activity Source: MGI
  • high-affinity glutamate transmembrane transporter activity Source: UniProtKB
  • L-glutamate transmembrane transporter activity Source: MGI
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • adult behavior Source: MGI
  • anion transmembrane transport Source: MGI
  • cellular response to extracellular stimulus Source: MGI
  • D-aspartate import Source: MGI
  • L-glutamate import Source: MGI
  • L-glutamate import across plasma membrane Source: UniProtKB
  • L-glutamate transmembrane transport Source: MGI
  • L-glutamate transport Source: MGI
  • multicellular organism aging Source: MGI
  • multicellular organism growth Source: MGI
  • nervous system development Source: MGI
  • positive regulation of glucose import Source: MGI
  • protein homotrimerization Source: UniProtKB
  • response to amino acid Source: MGI
  • response to drug Source: MGI
  • response to light stimulus Source: MGI
  • response to wounding Source: MGI
  • telencephalon development Source: MGI
  • visual behavior Source: MGI

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 2
Alternative name(s):
GLT-12 Publications
Sodium-dependent glutamate/aspartate transporter 2
Solute carrier family 1 member 2
Gene namesi
Name:Slc1a2
Synonyms:Eaat2, Glt1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:101931. Slc1a2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 44CytoplasmicSequence analysisAdd BLAST44
Transmembranei45 – 64HelicalSequence analysisAdd BLAST20
Transmembranei88 – 108HelicalSequence analysisAdd BLAST21
Transmembranei121 – 142HelicalSequence analysisAdd BLAST22
Transmembranei235 – 258Helical; Name=4By similarityAdd BLAST24
Transmembranei268 – 295Helical; Name=5By similarityAdd BLAST28
Transmembranei317 – 338Helical; Name=6By similarityAdd BLAST22
Intramembranei344 – 374Discontinuously helicalBy similarityAdd BLAST31
Transmembranei384 – 410Helical; Name=7By similarityAdd BLAST27
Intramembranei424 – 457Discontinuously helicalBy similarityAdd BLAST34
Transmembranei471 – 492Helical; Name=8By similarityAdd BLAST22

GO - Cellular componenti

  • axolemma Source: MGI
  • axon Source: MGI
  • cell surface Source: MGI
  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: MGI

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

No visible phenotype at birth (PubMed:9180080, PubMed:16880397). Mice are born at the expected Mendelian rate, but gain weight more slowly, especially after the first 30 days after birth (PubMed:9180080). Only half of them are still alive 60 days after birth (PubMed:9180080). Death is due to spontaneous epileptic seizures (PubMed:9180080). Besides, mutant mice display neuronal degeneration in the hippocampus CA1 field, probably due to impaired glutamate removal from the synaptic cleft (PubMed:9180080). Glutamate uptake by synaptosomes from mutant mouse brain cortex is reduced by 94% (PubMed:9180080). Mice deficient in both Slc1a2 and Slc1a3 die at about 17 dpc; they display defects in the brain structure that affects the brain cortex, hippocampus and olfactory bulb, due to impaired radial migration of neurons into the cortical plate and disorganization of the radial glial cell arrangement (PubMed:16880397).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi38C → S: Severely impairs glutamate uptake activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002020621 – 572Excitatory amino acid transporter 2Add BLAST572

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei3PhosphoserineBy similarity1
Modified residuei21PhosphoserineBy similarity1
Modified residuei24PhosphoserineCombined sources1
Modified residuei25PhosphoserineBy similarity1
Lipidationi38S-palmitoyl cysteine1 Publication1
Glycosylationi205N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi215N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei505PhosphoserineCombined sources1
Modified residuei520PhosphoserineCombined sources1
Modified residuei530PhosphoserineCombined sources1
Modified residuei532PhosphoserineCombined sources1
Modified residuei537PhosphotyrosineCombined sources1
Modified residuei542PhosphoserineCombined sources1
Modified residuei558PhosphoserineCombined sources1
Modified residuei562PhosphoserineCombined sources1

Post-translational modificationi

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

Keywords - PTMi

Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiP43006.
PeptideAtlasiP43006.
PRIDEiP43006.

PTM databases

iPTMnetiP43006.
PhosphoSitePlusiP43006.
SwissPalmiP43006.

Expressioni

Tissue specificityi

Detected in brain (PubMed:9180080). Detected in embryonic forebrain, especially in globus pallidus, perirhinal cortex, lateral hypothalamus, hippocampus, and on fimbria and axonal pathways connecting the neocortex, basal ganglia and thalamus (at protein level) (PubMed:16880397). Isoform GLT1 is expressed in the brain (PubMed:7698742, PubMed:7557442, PubMed:9373176, PubMed:9180080). Isoforms GLT-1A and GLT-1B are expressed in the liver (PubMed:9373176).5 Publications

Gene expression databases

BgeeiENSMUSG00000005089.
ExpressionAtlasiP43006. baseline and differential.
GenevisibleiP43006. MM.

Interactioni

Subunit structurei

Homotrimer (By similarity). Interacts with AJUBA (By similarity).By similarity

Protein-protein interaction databases

BioGridi203290. 7 interactors.
IntActiP43006. 8 interactors.
MINTiMINT-4093909.
STRINGi10090.ENSMUSP00000079100.

Structurei

3D structure databases

ProteinModelPortaliP43006.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni361 – 363Aspartate bindingBy similarity3
Regioni441 – 445Aspartate 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.
InParanoidiP43006.
KOiK05613.
OMAiVDWFMGI.
OrthoDBiEOG091G0UCE.
PhylomeDBiP43006.
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.

Sequences (3)i

Sequence statusi: Complete.

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

Isoform Glt-1 (identifier: P43006-1) [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 SHLSSDEPKH RNLGMRMCDK LGKNLLLSLT
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
SEEANTTKAV ISMLNETMNE APEETKIVIK KGLEFKDGMN VLGLIGFFIA
260 270 280 290 300
FGIAMGKMGE QAKLMVEFFN ILNEIVMKLV IMIMWYSPLG IACLICGKII
310 320 330 340 350
AIKDLEVVAR QLGMYMITVI VGLIIHGGIF LPLIYFVVTR KNPFSFFAGI
360 370 380 390 400
FQAWITALGT ASSAGTLPVT FRCLEDNLGI DKRVTRFVLP VGATINMDGT
410 420 430 440 450
ALYEAVAAIF IAQMNGVILD GGQIVTVSLT ATLASIGAAS IPSAGLVTML
460 470 480 490 500
LILTAVGLPT EDISLLVAVD WLLDRMRTSV NVVGDSFGAG IVYHLSKSEL
510 520 530 540 550
DTIDSQHRMQ EDIEMTKTQS IYDDKNHRES NSNQCVYAAH NSVVIDECKV
560 570
TLAANGKSAD CSVEEEPWKR EK
Length:572
Mass (Da):62,030
Last modified:November 1, 1995 - v1
Checksum:i13C7C30DED40CA81
GO
Isoform Glt-1A (identifier: P43006-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: MASTEG → MVS

Show »
Length:569
Mass (Da):61,771
Checksum:i930251320261AB8B
GO
Isoform Glt-1B (identifier: P43006-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-6: MASTEG → MVS
     551-572: TLAANGKSADCSVEEEPWKREK → PFPFLDIETCI

Show »
Length:558
Mass (Da):60,617
Checksum:iE82305D0F6E4BD91
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti26D → E in AAA91643 (PubMed:7557442).Curated1
Sequence conflicti62G → R in AAA91643 (PubMed:7557442).Curated1
Sequence conflicti112A → V in AAA91643 (PubMed:7557442).Curated1
Sequence conflicti454T → I in AAB71737 (Ref. 4) Curated1
Sequence conflicti525K → L in AAB71737 (Ref. 4) Curated1
Sequence conflicti572K → EFD in AAA91643 (PubMed:7557442).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0062641 – 6MASTEG → MVS in isoform Glt-1A and isoform Glt-1B. Curated6
Alternative sequenceiVSP_006265551 – 572TLAAN…WKREK → PFPFLDIETCI in isoform Glt-1B. CuratedAdd BLAST22

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U11763 mRNA. Translation: AAA77673.1.
D43796 mRNA. Translation: BAA07854.1.
U24699 mRNA. Translation: AAA91643.1.
U75372 mRNA. Translation: AAB71737.1.
U75373 mRNA. Translation: AAB71738.1.
AB007810 mRNA. Translation: BAA23770.1.
AB007811 mRNA. Translation: BAA23771.1.
AB007812 mRNA. Translation: BAA23772.1.
CCDSiCCDS16469.1. [P43006-3]
CCDS38188.1. [P43006-1]
CCDS38189.1. [P43006-2]
PIRiA55676.
JC4262.
RefSeqiNP_001070982.1. NM_001077514.3. [P43006-1]
NP_001070983.1. NM_001077515.2. [P43006-2]
NP_035523.1. NM_011393.2. [P43006-3]
UniGeneiMm.267547.
Mm.371582.
Mm.453107.
Mm.453110.

Genome annotation databases

EnsembliENSMUST00000005220; ENSMUSP00000005220; ENSMUSG00000005089. [P43006-3]
ENSMUST00000080210; ENSMUSP00000079100; ENSMUSG00000005089. [P43006-1]
ENSMUST00000111212; ENSMUSP00000106843; ENSMUSG00000005089. [P43006-2]
GeneIDi20511.
KEGGimmu:20511.
UCSCiuc008lid.2. mouse. [P43006-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiEAA2_MOUSE
AccessioniPrimary (citable) accession number: P43006
Secondary accession number(s): O35877, O54686, O54687
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: August 30, 2017
This is version 159 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, Direct protein sequencing, 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