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P43003 (EAA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SLC1A3
Synonyms:EAAT1, GLAST, GLAST1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length542 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

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

Post-translational modification

Glycosylated.

Involvement in disease

Episodic ataxia 6 (EA6) [MIM:612656]: A disorder characterized by episodic ataxia, seizures, migraine and alternating hemiplegia.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11

Sequence similarities

Belongs to the sodium:dicarboxylate (SDF) symporter (TC 2.A.23) family. SLC1A3 subfamily. [View classification]

Ontologies

Keywords
   Biological processSymport
Transport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainTransmembrane
Transmembrane helix
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processD-aspartate import

Inferred from direct assay Ref.2. Source: UniProtKB

L-glutamate import

Inferred from direct assay Ref.2. Source: UniProtKB

auditory behavior

Inferred from electronic annotation. Source: Ensembl

cell morphogenesis involved in neuron differentiation

Inferred from electronic annotation. Source: Ensembl

cranial nerve development

Inferred from electronic annotation. Source: Ensembl

gamma-aminobutyric acid biosynthetic process

Inferred from electronic annotation. Source: Ensembl

glutamate biosynthetic process

Inferred from electronic annotation. Source: Ensembl

ion transport

Traceable author statement. Source: Reactome

neuromuscular process controlling balance

Inferred from electronic annotation. Source: Ensembl

neurotransmitter uptake

Traceable author statement Ref.4. Source: ProtInc

positive regulation of synaptic transmission

Inferred from electronic annotation. Source: Ensembl

response to antibiotic

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to light stimulus

Inferred from electronic annotation. Source: Ensembl

response to wounding

Inferred from electronic annotation. Source: Ensembl

sensory perception of sound

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Traceable author statement Ref.2. Source: ProtInc

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentcell projection

Inferred from electronic annotation. Source: Ensembl

cell surface

Inferred from electronic annotation. Source: Ensembl

fibril

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Traceable author statement Ref.2. Source: ProtInc

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionL-glutamate transmembrane transporter activity

Inferred from direct assay Ref.2. Source: BHF-UCL

glutamate binding

Inferred from electronic annotation. Source: Ensembl

high-affinity glutamate transmembrane transporter activity

Inferred from electronic annotation. Source: Ensembl

sodium:dicarboxylate symporter activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P43003-1)

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.
Isoform 2 (identifier: P43003-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 542542Excitatory amino acid transporter 1
PRO_0000202057

Regions

Topological domain1 – 4747Cytoplasmic Potential
Transmembrane48 – 6821Helical; Potential
Transmembrane91 – 11121Helical; Potential
Transmembrane123 – 14523Helical; Potential
Topological domain146 – 23792Extracellular Potential
Transmembrane238 – 26023Helical; Potential
Transmembrane281 – 30222Helical; Potential
Transmembrane319 – 34022Helical; Potential

Natural variations

Alternative sequence430 – 47546SITAT…VDWFL → R in isoform 2.
VSP_043913
Natural variant2191E → D.
Corresponds to variant rs2032892 [ dbSNP | Ensembl ].
VAR_011877
Natural variant2901P → R in EA6. Ref.11
VAR_031733

Experimental info

Sequence conflict3661S → CT Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 6E9F62D35A3A5A29

FASTA54259,572
        10         20         30         40         50         60 
MTKSNGEEPK MGGRMERFQQ GVRKRTLLAK KKVQNITKED VKSYLFRNAF VLLTVTAVIV 

        70         80         90        100        110        120 
GTILGFTLRP YRMSYREVKY FSFPGELLMR MLQMLVLPLI ISSLVTGMAA LDSKASGKMG 

       130        140        150        160        170        180 
MRAVVYYMTT TIIAVVIGII IVIIIHPGKG TKENMHREGK IVRVTAADAF LDLIRNMFPP 

       190        200        210        220        230        240 
NLVEACFKQF KTNYEKRSFK VPIQANETLV GAVINNVSEA METLTRITEE LVPVPGSVNG 

       250        260        270        280        290        300 
VNALGLVVFS MCFGFVIGNM KEQGQALREF FDSLNEAIMR LVAVIMWYAP VGILFLIAGK 

       310        320        330        340        350        360 
IVEMEDMGVI GGQLAMYTVT VIVGLLIHAV IVLPLLYFLV TRKNPWVFIG GLLQALITAL 

       370        380        390        400        410        420 
GTSSSSATLP ITFKCLEENN GVDKRVTRFV LPVGATINMD GTALYEALAA IFIAQVNNFE 

       430        440        450        460        470        480 
LNFGQIITIS ITATAASIGA AGIPQAGLVT MVIVLTSVGL PTDDITLIIA VDWFLDRLRT 

       490        500        510        520        530        540 
TTNVLGDSLG AGIVEHLSRH ELKNRDVEMG NSVIEENEMK KPYQLIAQDN ETEKPIDSET 


KM 

« Hide

Isoform 2 (EAAT1ex9skip) [UniParc].

Checksum: 7C21EC2B467E1C11
Show »

FASTA49755,149

References

« Hide 'large scale' references
[1]"Cloning and characterization of a glutamate transporter cDNA from human cerebellum."
Shashidharan P., Plaitakis A.
Biochim. Biophys. Acta 1216:161-164(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Cerebellum.
[2]"Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex."
Arriza J.L., Fairman W.A., Wendy A., Wadiche J.I., Murdoch G.H., Kavanaugh M.P., Amara S.G.
J. Neurosci. 14:5559-5569(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain cortex.
[3]"Cloning and expression of a human glutamate transporter."
Kawakami H., Tanaka K., Nakayama T., Inoue K., Nakamura S.
Biochem. Biophys. Res. Commun. 199:171-176(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[4]"Human high affinity, Na(+)-dependent L-glutamate/L-aspartate transporter GLAST-1 (EAAT-1): gene structure and localization to chromosome 5p11-p12."
Stoffel W., Sasse J., Dueker M., Mueller R., Hofmann K.O., Fink T., Lichter P.
FEBS Lett. 386:189-193(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"A novel alternative splicing form of excitatory amino acid transporter 1 is a negative regulator of glutamate uptake."
Vallejo-Illarramendi A., Domercq M., Matute C.
J. Neurochem. 95:341-348(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Cerebellum.
[7]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures."
Jen J.C., Wan J., Palos T.P., Howard B.D., Baloh R.W.
Neurology 65:529-534(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EA6 ARG-290.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L19158 mRNA. No translation available.
U03504 mRNA. Translation: AAA50428.1.
D26443 mRNA. Translation: BAA05462.1.
Z31713 expand/collapse EMBL AC list , 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.
CCDSCCDS3919.1. [P43003-1]
CCDS54844.1. [P43003-2]
PIRS38353.
RefSeqNP_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_005248342.1. [P43003-1]
XP_006714551.1. XM_006714488.1. [P43003-1]
UniGeneHs.481918.

3D structure databases

ProteinModelPortalP43003.
SMRP43003. Positions 55-494.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112398. 5 interactions.
IntActP43003. 1 interaction.
MINTMINT-5004226.
STRING9606.ENSP00000265113.

Chemistry

BindingDBP43003.
ChEMBLCHEMBL3085.
DrugBankDB00142. L-Glutamic Acid.
GuidetoPHARMACOLOGY868.

Protein family/group databases

TCDB2.A.23.2.6. the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.

PTM databases

PhosphoSiteP43003.

Polymorphism databases

DMDM1169458.

Proteomic databases

MaxQBP43003.
PaxDbP43003.
PRIDEP43003.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265113; ENSP00000265113; ENSG00000079215. [P43003-1]
ENST00000381918; ENSP00000371343; ENSG00000079215. [P43003-2]
GeneID6507.
KEGGhsa:6507.
UCSCuc003jkj.4. human. [P43003-1]
uc010iuy.3. human. [P43003-2]

Organism-specific databases

CTD6507.
GeneCardsGC05P036606.
HGNCHGNC:10941. SLC1A3.
HPACAB002573.
HPA037467.
HPA037468.
MIM600111. gene.
612656. phenotype.
neXtProtNX_P43003.
Orphanet2131. Alternating hemiplegia of childhood.
209967. Episodic ataxia type 6.
PharmGKBPA35828.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1301.
HOGENOMHOG000208776.
HOVERGENHBG000080.
InParanoidP43003.
KOK05614.
OMATLRPYRM.
OrthoDBEOG7RV9G2.
PhylomeDBP43003.
TreeFamTF315206.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.
REACT_15518. Transmembrane transport of small molecules.
REACT_19419. Amino acid and oligopeptide SLC transporters.

Gene expression databases

ArrayExpressP43003.
BgeeP43003.
CleanExHS_SLC1A3.
GenevestigatorP43003.

Family and domain databases

Gene3D1.10.3860.10. 2 hits.
InterProIPR001991. Na-dicarboxylate_symporter.
IPR018107. Na-dicarboxylate_symporter_CS.
[Graphical view]
PANTHERPTHR11958. PTHR11958. 1 hit.
PfamPF00375. SDF. 1 hit.
[Graphical view]
PRINTSPR00173. EDTRNSPORT.
SUPFAMSSF118215. SSF118215. 2 hits.
PROSITEPS00713. NA_DICARBOXYL_SYMP_1. 1 hit.
PS00714. NA_DICARBOXYL_SYMP_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSLC1A3. human.
GeneWikiGlutamate_aspartate_transporter.
GenomeRNAi6507.
NextBio25301.
PROP43003.
SOURCESearch...

Entry information

Entry nameEAA1_HUMAN
AccessionPrimary (citable) accession number: P43003
Secondary accession number(s): B2R5T3, Q4JCQ8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 9, 2014
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM