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Protein

Excitatory amino acid transporter 3

Gene

Slc1a1

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:12119102, PubMed:18684713). Can also transport L-cysteine. 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 an important role in L-glutamate and L-aspartate reabsorption in renal tubuli (PubMed:9233792). 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:9233792). Negatively regulated by ARL6IP5 (PubMed:12119102).By similarity3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi361Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi363Sodium 2; via carbonyl oxygenBy similarity1
Metal bindingi365Sodium 1By similarity1
Binding sitei369AspartateBy similarity1
Binding sitei443AspartateBy similarity1
Metal bindingi450Sodium 1; via carbonyl oxygenBy similarity1
Binding sitei450AspartateBy similarity1
Metal bindingi454Sodium 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-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 3
Alternative name(s):
Excitatory amino-acid carrier 11 Publication
Sodium-dependent glutamate/aspartate transporter 3
Solute carrier family 1 member 1
Gene namesi
Name:Slc1a1
Synonyms:Eaac11 Publication, Eaat3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:105083. Slc1a1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 18CytoplasmicCuratedAdd BLAST18
Transmembranei19 – 38HelicalSequence analysisAdd BLAST20
Topological domaini39 – 61ExtracellularCuratedAdd BLAST23
Transmembranei62 – 82HelicalSequence analysisAdd BLAST21
Topological domaini83 – 93CytoplasmicCuratedAdd BLAST11
Transmembranei94 – 114HelicalSequence analysisAdd BLAST21
Topological domaini115 – 204ExtracellularCuratedAdd BLAST90
Transmembranei205 – 228Helical; Name=4By similarityAdd BLAST24
Topological domaini229 – 237CytoplasmicCurated9
Transmembranei238 – 265Helical; Name=5By similarityAdd BLAST28
Topological domaini266 – 285ExtracellularCuratedAdd BLAST20
Transmembranei286 – 307Helical; Name=6By similarityAdd BLAST22
Topological domaini308 – 312CytoplasmicCurated5
Intramembranei313 – 343Discontinuously helicalBy similarityAdd BLAST31
Topological domaini344 – 352CytoplasmicCurated9
Transmembranei353 – 379Helical; Name=7By similarityAdd BLAST27
Topological domaini380 – 392ExtracellularCuratedAdd BLAST13
Intramembranei393 – 426Discontinuously helicalBy similarityAdd BLAST34
Topological domaini427 – 439ExtracellularCuratedAdd BLAST13
Transmembranei440 – 461Helical; Name=8By similarityAdd BLAST22
Topological domaini462 – 523CytoplasmicCuratedAdd BLAST62

GO - Cellular componenti

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

No visible phenotype at birth. Mice are born at the expected Mendelian rate, are viable and fertile, and do not develop any neurological symptoms with increasing age. They show decreased spontaneous locomotor activity. Besides, urinary excretion of glutamate and aspartate are strongly increased, but glutamate and aspartate serum levels are normal.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002020661 – 523Excitatory amino acid transporter 3Add BLAST523

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi128N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi178N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi194N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei516PhosphoserineCombined sources1
Modified residuei521PhosphoserineCombined sources1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP51906.
PaxDbiP51906.
PeptideAtlasiP51906.
PRIDEiP51906.

PTM databases

iPTMnetiP51906.
PhosphoSitePlusiP51906.

Expressioni

Tissue specificityi

Expressed in whole brain, brain cortex, hippocampus, cerebellum, lung, kidney, small intestine and skeletal muscle.2 Publications

Gene expression databases

BgeeiENSMUSG00000024935.
GenevisibleiP51906. MM.

Interactioni

Subunit structurei

Homotrimer (Probable). Interacts with ARL6IP5 (PubMed:12119102, PubMed:18684713).Curated2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HccsP537025EBI-8580001,EBI-8579982

Protein-protein interaction databases

IntActiP51906. 1 interactor.
MINTiMINT-2839452.
STRINGi10090.ENSMUSP00000025875.

Structurei

3D structure databases

ProteinModelPortaliP51906.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni330 – 332Aspartate bindingBy similarity3
Regioni410 – 414Aspartate 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.
InParanoidiP51906.
KOiK05612.
OMAiYLYIAVI.
OrthoDBiEOG091G0UCE.
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.

P51906-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGKPTSSGCD WRRFLRNHWL LLSTVAAVVL GIVLGVVVRG HSELSNLDKF
60 70 80 90 100
YFAFPGEILM RMLKLVILPL IVSSMITGVA ALDSNVSGKI GLRAVVYYFS
110 120 130 140 150
TTVIAVILGI VLVVSIKPGV TQKVNDINRT GKTPEVSTMD AMLDLIRNMF
160 170 180 190 200
PENLVQACFQ QYKTKREEVK PVGDPGGNAT EVSVTTAMTT MSENKTKEYK
210 220 230 240 250
IVGLYSDGIN VLGLIIFCLV FGLVIGKMGE KGQILVDFFN ALSDATMKIV
260 270 280 290 300
QIIMCYMPIG ILFLIAGKII EVEDWEIFRK LGLYMATVLS GLAIHSLIVL
310 320 330 340 350
PLLYFIVVRK NPFRFALGMA QALLTALMIS SSSATLPVTF RCAEEKNQVD
360 370 380 390 400
KRITRFVLPV GATINMDGTA LYEAVAAVFI AQLNGLDLSI GQIVTISITA
410 420 430 440 450
TAASIGAAGV PQAGLVTMVI VLSAVGLPAE DVTLIIAVDW LLDRFRTMVN
460 470 480 490 500
VLGDAFGTGI VEKLSKKELE QMDVSSEVNI VNPFALEPTT LDNEDSDTKK
510 520
SYVNGGFAVD KSDTISFTQT SQF
Length:523
Mass (Da):56,694
Last modified:July 27, 2011 - v2
Checksum:i46F35480465E5A82
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti121T → A in AAB71742 (Ref. 2) Curated1
Sequence conflicti139M → I in BAA07855 (PubMed:7766664).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D43797 mRNA. Translation: BAA07855.1.
U73521 mRNA. Translation: AAB80694.1.
U75217 Genomic DNA. Translation: AAB71742.1.
CH466534 Genomic DNA. Translation: EDL41660.1.
BC065099 mRNA. Translation: AAH65099.1.
CCDSiCCDS29727.1.
PIRiS55677.
RefSeqiNP_033225.1. NM_009199.2.
UniGeneiMm.246670.

Genome annotation databases

EnsembliENSMUST00000025875; ENSMUSP00000025875; ENSMUSG00000024935.
GeneIDi20510.
KEGGimmu:20510.
UCSCiuc008hcl.1. mouse.

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 nameiEAA3_MOUSE
AccessioniPrimary (citable) accession number: P51906
Secondary accession number(s): O35869, O35875, Q6P1F7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 27, 2011
Last modified: July 5, 2017
This is version 135 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, 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