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Protein

Excitatory amino acid transporter 1

Gene

SLC1A3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transports L-glutamate and also L- and D-aspartate. Essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. Acts as a symport by cotransporting sodium.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Symport, Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000079215-MONOMER.
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.
SIGNORiP43003.

Protein family/group databases

TCDBi2.A.23.2.6. the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Excitatory amino acid transporter 1
Alternative name(s):
Sodium-dependent glutamate/aspartate transporter 1
Short name:
GLAST-1
Solute carrier family 1 member 3
Gene namesi
Name:SLC1A3
Synonyms:EAAT1, GLAST, GLAST1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:10941. SLC1A3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 47CytoplasmicSequence analysisAdd BLAST47
Transmembranei48 – 68HelicalSequence analysisAdd BLAST21
Transmembranei91 – 111HelicalSequence analysisAdd BLAST21
Transmembranei123 – 145HelicalSequence analysisAdd BLAST23
Topological domaini146 – 237ExtracellularSequence analysisAdd BLAST92
Transmembranei238 – 260HelicalSequence analysisAdd BLAST23
Transmembranei281 – 302HelicalSequence analysisAdd BLAST22
Transmembranei319 – 340HelicalSequence analysisAdd BLAST22

GO - Cellular componenti

  • cell surface Source: Ensembl
  • fibril Source: Ensembl
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: ProtInc
  • neuronal cell body Source: Ensembl
  • neuron projection Source: Ensembl
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Episodic ataxia 6 (EA6)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by episodic ataxia, seizures, migraine and alternating hemiplegia.
See also OMIM:612656
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_031733290P → R in EA6. 1 PublicationCorresponds to variant rs137852619dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi6507.
MalaCardsiSLC1A3.
MIMi612656. phenotype.
OpenTargetsiENSG00000079215.
Orphaneti2131. Alternating hemiplegia of childhood.
209967. Episodic ataxia type 6.
PharmGKBiPA35828.

Chemistry databases

ChEMBLiCHEMBL3085.
GuidetoPHARMACOLOGYi868.

Polymorphism and mutation databases

BioMutaiSLC1A3.
DMDMi1169458.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002020571 – 542Excitatory amino acid transporter 1Add BLAST542

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei512PhosphoserineCombined sources1

Post-translational modificationi

Glycosylated.

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP43003.
PaxDbiP43003.
PeptideAtlasiP43003.
PRIDEiP43003.

PTM databases

iPTMnetiP43003.
PhosphoSitePlusiP43003.
SwissPalmiP43003.

Expressioni

Tissue specificityi

Highly expressed in cerebellum, but also found in frontal cortex, hippocampus and basal ganglia.

Gene expression databases

BgeeiENSG00000079215.
CleanExiHS_SLC1A3.
ExpressionAtlasiP43003. baseline and differential.
GenevisibleiP43003. HS.

Organism-specific databases

HPAiCAB002573.
HPA037467.
HPA037468.

Interactioni

Protein-protein interaction databases

BioGridi112398. 7 interactors.
IntActiP43003. 3 interactors.
MINTiMINT-5004226.
STRINGi9606.ENSP00000265113.

Chemistry databases

BindingDBiP43003.

Structurei

3D structure databases

ProteinModelPortaliP43003.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3787. Eukaryota.
COG1301. LUCA.
GeneTreeiENSGT00760000119117.
HOGENOMiHOG000208776.
HOVERGENiHBG000080.
InParanoidiP43003.
KOiK05614.
OMAiFKTSYEK.
OrthoDBiEOG091G0UCE.
PhylomeDBiP43003.
TreeFamiTF315206.

Family and domain databases

Gene3Di1.10.3860.10. 2 hits.
InterProiIPR001991. Na-dicarboxylate_symporter.
IPR018107. Na-dicarboxylate_symporter_CS.
[Graphical view]
PANTHERiPTHR11958. PTHR11958. 2 hits.
PfamiPF00375. SDF. 1 hit.
[Graphical view]
PRINTSiPR00173. EDTRNSPORT.
SUPFAMiSSF118215. SSF118215. 2 hits.
PROSITEiPS00713. NA_DICARBOXYL_SYMP_1. 1 hit.
PS00714. NA_DICARBOXYL_SYMP_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P43003-1) [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
MTKSNGEEPK MGGRMERFQQ GVRKRTLLAK KKVQNITKED VKSYLFRNAF
60 70 80 90 100
VLLTVTAVIV GTILGFTLRP YRMSYREVKY FSFPGELLMR MLQMLVLPLI
110 120 130 140 150
ISSLVTGMAA LDSKASGKMG MRAVVYYMTT TIIAVVIGII IVIIIHPGKG
160 170 180 190 200
TKENMHREGK IVRVTAADAF LDLIRNMFPP NLVEACFKQF KTNYEKRSFK
210 220 230 240 250
VPIQANETLV GAVINNVSEA METLTRITEE LVPVPGSVNG VNALGLVVFS
260 270 280 290 300
MCFGFVIGNM KEQGQALREF FDSLNEAIMR LVAVIMWYAP VGILFLIAGK
310 320 330 340 350
IVEMEDMGVI GGQLAMYTVT VIVGLLIHAV IVLPLLYFLV TRKNPWVFIG
360 370 380 390 400
GLLQALITAL GTSSSSATLP ITFKCLEENN GVDKRVTRFV LPVGATINMD
410 420 430 440 450
GTALYEALAA IFIAQVNNFE LNFGQIITIS ITATAASIGA AGIPQAGLVT
460 470 480 490 500
MVIVLTSVGL PTDDITLIIA VDWFLDRLRT TTNVLGDSLG AGIVEHLSRH
510 520 530 540
ELKNRDVEMG NSVIEENEMK KPYQLIAQDN ETEKPIDSET KM
Length:542
Mass (Da):59,572
Last modified:November 1, 1995 - v1
Checksum:i6E9F62D35A3A5A29
GO
Isoform 2 (identifier: P43003-2) [UniParc]FASTAAdd to basket
Also known as: EAAT1ex9skip

The sequence of this isoform differs from the canonical sequence as follows:
     430-475: SITATAASIGAAGIPQAGLVTMVIVLTSVGLPTDDITLIIAVDWFL → R

Note: Expressed throughout the CNS, both in gray matter and axonal tracts, at levels ranging between 10% and 20% of isoform 1. Localizes to ER, has no functional glutamate uptake activity, and exerts a dominant negative effect isoform 1.
Show »
Length:497
Mass (Da):55,149
Checksum:i7C21EC2B467E1C11
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti366S → CT (PubMed:8218410).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_011877219E → D.Corresponds to variant rs2032892dbSNPEnsembl.1
Natural variantiVAR_031733290P → R in EA6. 1 PublicationCorresponds to variant rs137852619dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_043913430 – 475SITAT…VDWFL → R in isoform 2. 1 PublicationAdd BLAST46

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L19158 mRNA. No translation available.
U03504 mRNA. Translation: AAA50428.1.
D26443 mRNA. Translation: BAA05462.1.
Z31713
, Z31703, Z31704, Z31705, Z31706, Z31707, Z31708, Z31709, Z31710 Genomic DNA. Translation: CAA83507.1.
AY954110 mRNA. Translation: AAY28724.1.
AK312304 mRNA. Translation: BAG35230.1.
AC008957 Genomic DNA. No translation available.
AC010631 Genomic DNA. No translation available.
CH471119 Genomic DNA. Translation: EAW55945.1.
CCDSiCCDS3919.1. [P43003-1]
CCDS54844.1. [P43003-2]
PIRiS38353.
RefSeqiNP_001160167.1. NM_001166695.2. [P43003-2]
NP_001276869.1. NM_001289940.1.
NP_004163.3. NM_004172.4. [P43003-1]
XP_005248399.1. XM_005248342.2. [P43003-1]
UniGeneiHs.481918.

Genome annotation databases

EnsembliENST00000265113; ENSP00000265113; ENSG00000079215. [P43003-1]
ENST00000381918; ENSP00000371343; ENSG00000079215. [P43003-2]
GeneIDi6507.
KEGGihsa:6507.
UCSCiuc003jkj.4. human. [P43003-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L19158 mRNA. No translation available.
U03504 mRNA. Translation: AAA50428.1.
D26443 mRNA. Translation: BAA05462.1.
Z31713
, Z31703, Z31704, Z31705, Z31706, Z31707, Z31708, Z31709, Z31710 Genomic DNA. Translation: CAA83507.1.
AY954110 mRNA. Translation: AAY28724.1.
AK312304 mRNA. Translation: BAG35230.1.
AC008957 Genomic DNA. No translation available.
AC010631 Genomic DNA. No translation available.
CH471119 Genomic DNA. Translation: EAW55945.1.
CCDSiCCDS3919.1. [P43003-1]
CCDS54844.1. [P43003-2]
PIRiS38353.
RefSeqiNP_001160167.1. NM_001166695.2. [P43003-2]
NP_001276869.1. NM_001289940.1.
NP_004163.3. NM_004172.4. [P43003-1]
XP_005248399.1. XM_005248342.2. [P43003-1]
UniGeneiHs.481918.

3D structure databases

ProteinModelPortaliP43003.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112398. 7 interactors.
IntActiP43003. 3 interactors.
MINTiMINT-5004226.
STRINGi9606.ENSP00000265113.

Chemistry databases

BindingDBiP43003.
ChEMBLiCHEMBL3085.
GuidetoPHARMACOLOGYi868.

Protein family/group databases

TCDBi2.A.23.2.6. the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.

PTM databases

iPTMnetiP43003.
PhosphoSitePlusiP43003.
SwissPalmiP43003.

Polymorphism and mutation databases

BioMutaiSLC1A3.
DMDMi1169458.

Proteomic databases

MaxQBiP43003.
PaxDbiP43003.
PeptideAtlasiP43003.
PRIDEiP43003.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265113; ENSP00000265113; ENSG00000079215. [P43003-1]
ENST00000381918; ENSP00000371343; ENSG00000079215. [P43003-2]
GeneIDi6507.
KEGGihsa:6507.
UCSCiuc003jkj.4. human. [P43003-1]

Organism-specific databases

CTDi6507.
DisGeNETi6507.
GeneCardsiSLC1A3.
HGNCiHGNC:10941. SLC1A3.
HPAiCAB002573.
HPA037467.
HPA037468.
MalaCardsiSLC1A3.
MIMi600111. gene.
612656. phenotype.
neXtProtiNX_P43003.
OpenTargetsiENSG00000079215.
Orphaneti2131. Alternating hemiplegia of childhood.
209967. Episodic ataxia type 6.
PharmGKBiPA35828.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3787. Eukaryota.
COG1301. LUCA.
GeneTreeiENSGT00760000119117.
HOGENOMiHOG000208776.
HOVERGENiHBG000080.
InParanoidiP43003.
KOiK05614.
OMAiFKTSYEK.
OrthoDBiEOG091G0UCE.
PhylomeDBiP43003.
TreeFamiTF315206.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000079215-MONOMER.
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.
SIGNORiP43003.

Miscellaneous databases

ChiTaRSiSLC1A3. human.
GeneWikiiGlutamate_aspartate_transporter.
GenomeRNAii6507.
PROiP43003.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000079215.
CleanExiHS_SLC1A3.
ExpressionAtlasiP43003. baseline and differential.
GenevisibleiP43003. HS.

Family and domain databases

Gene3Di1.10.3860.10. 2 hits.
InterProiIPR001991. Na-dicarboxylate_symporter.
IPR018107. Na-dicarboxylate_symporter_CS.
[Graphical view]
PANTHERiPTHR11958. PTHR11958. 2 hits.
PfamiPF00375. SDF. 1 hit.
[Graphical view]
PRINTSiPR00173. EDTRNSPORT.
SUPFAMiSSF118215. SSF118215. 2 hits.
PROSITEiPS00713. NA_DICARBOXYL_SYMP_1. 1 hit.
PS00714. NA_DICARBOXYL_SYMP_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiEAA1_HUMAN
AccessioniPrimary (citable) accession number: P43003
Secondary accession number(s): B2R5T3, Q4JCQ8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 30, 2016
This is version 157 of the entry and version 1 of the sequence. [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 5
    Human chromosome 5: 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

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.