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P43004 (EAA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Excitatory amino acid transporter 2
Alternative name(s):
Glutamate/aspartate transporter II
Sodium-dependent glutamate/aspartate transporter 2
Solute carrier family 1 member 2
Gene names
Name:SLC1A2
Synonyms:EAAT2, GLT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length574 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.

Subunit structure

Homotrimer. Isoform 3 can oligomerize with isoform 1. Interacts with AJUBA By similarity. Ref.10 Ref.11

Subcellular location

Membrane; Multi-pass membrane protein.

Post-translational modification

Glycosylated.

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

Sequence similarities

Belongs to the sodium:dicarboxylate (SDF) symporter (TC 2.A.23) family. SLC1A2 subfamily. [View classification]

Ontologies

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

Inferred from direct assay Ref.1. Source: UniProtKB

L-glutamate import

Inferred from direct assay Ref.1. Source: UniProtKB

adult behavior

Inferred from electronic annotation. Source: Ensembl

cellular response to extracellular stimulus

Inferred from electronic annotation. Source: Ensembl

ion transport

Traceable author statement. Source: Reactome

multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

multicellular organismal aging

Inferred from electronic annotation. Source: Ensembl

positive regulation of glucose import

Inferred from electronic annotation. Source: Ensembl

response to amino acid

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to wounding

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Traceable author statement Ref.1. Source: ProtInc

telencephalon development

Inferred from electronic annotation. Source: Ensembl

transmembrane transport

Traceable author statement. Source: Reactome

visual behavior

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentaxolemma

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionL-glutamate transmembrane transporter activity

Inferred from direct assay Ref.1. Source: BHF-UCL

glutamate:sodium symporter activity

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 19527721. Source: IntAct

sodium:dicarboxylate symporter activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MAPTP106364EBI-3440986,EBI-366182

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P43004-1)

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: P43004-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: Missing.
Isoform 3 (identifier: P43004-3)

Also known as: EEAT2b;

The sequence of this isoform differs from the canonical sequence as follows:
     553-574: TLAANGKSADCSVEEEPWKREK → HFPFMDIETCI

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 574574Excitatory amino acid transporter 2
PRO_0000202061

Regions

Topological domain1 – 4444Cytoplasmic Potential
Transmembrane45 – 6420Helical; Potential
Transmembrane88 – 10821Helical; Potential
Transmembrane121 – 14222Helical; Potential
Topological domain143 – 23997Extracellular Potential
Transmembrane240 – 25920Helical; Potential
Transmembrane280 – 30122Helical; Potential
Transmembrane317 – 33923Helical; Potential
Transmembrane406 – 43025Helical; Potential
Transmembrane437 – 45923Helical; Potential

Amino acid modifications

Modified residue5391Phosphotyrosine By similarity
Lipidation381S-palmitoyl cysteine By similarity
Glycosylation2061N-linked (GlcNAc...) Potential
Glycosylation2161N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 99Missing in isoform 2.
VSP_037152
Alternative sequence553 – 57422TLAAN…WKREK → HFPFMDIETCI in isoform 3.
VSP_054934

Experimental info

Sequence conflict71A → T in BAG60911. Ref.6
Sequence conflict191H → P in AAA50429. Ref.1
Sequence conflict271E → G in CAA83532. Ref.3
Sequence conflict501T → Q in AAA18900. Ref.2
Sequence conflict581A → S in AAA18900. Ref.2
Sequence conflict1411A → G in CAA83532. Ref.3
Sequence conflict1551P → A in CAA83532. Ref.3
Sequence conflict2111V → E in AAA50429. Ref.1
Sequence conflict253 – 2553GIA → AIP in CAA83532. Ref.3
Sequence conflict263 – 28927AKLMV…MWYSP → GQADGGFLQHFERDCNEVSD HDHVVLS in CAA83532. Ref.3
Sequence conflict3471F → L in AAA50429. Ref.1
Sequence conflict5391Y → F in CAA83532. Ref.3
Sequence conflict5561A → G in CAA83532. Ref.3
Sequence conflict563 – 5653CSV → RVL in CAA83532. Ref.3
Sequence conflict5701W → G in CAA83532. Ref.3

Sequences

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

Last modified July 15, 1998. Version 2.
Checksum: C8104E6727979435

FASTA57462,104
        10         20         30         40         50         60 
MASTEGANNM PKQVEVRMHD SHLGSEEPKH RHLGLRLCDK LGKNLLLTLT VFGVILGAVC 

        70         80         90        100        110        120 
GGLLRLASPI HPDVVMLIAF PGDILMRMLK MLILPLIISS LITGLSGLDA KASGRLGTRA 

       130        140        150        160        170        180 
MVYYMSTTII AAVLGVILVL AIHPGNPKLK KQLGPGKKND EVSSLDAFLD LIRNLFPENL 

       190        200        210        220        230        240 
VQACFQQIQT VTKKVLVAPP PDEEANATSA VVSLLNETVT EVPEETKMVI KKGLEFKDGM 

       250        260        270        280        290        300 
NVLGLIGFFI AFGIAMGKMG DQAKLMVDFF NILNEIVMKL VIMIMWYSPL GIACLICGKI 

       310        320        330        340        350        360 
IAIKDLEVVA RQLGMYMVTV IIGLIIHGGI FLPLIYFVVT RKNPFSFFAG IFQAWITALG 

       370        380        390        400        410        420 
TASSAGTLPV TFRCLEENLG IDKRVTRFVL PVGATINMDG TALYEAVAAI FIAQMNGVVL 

       430        440        450        460        470        480 
DGGQIVTVSL TATLASVGAA SIPSAGLVTM LLILTAVGLP TEDISLLVAV DWLLDRMRTS 

       490        500        510        520        530        540 
VNVVGDSFGA GIVYHLSKSE LDTIDSQHRV HEDIEMTKTQ SIYDDMKNHR ESNSNQCVYA 

       550        560        570 
AHNSVIVDEC KVTLAANGKS ADCSVEEEPW KREK 

« Hide

Isoform 2 [UniParc].

Checksum: A7286207F550252F
Show »

FASTA56561,228
Isoform 3 (EEAT2b) [UniParc].

Checksum: C13903644ADD1802
Show »

FASTA56361,008

References

« Hide 'large scale' references
[1]"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.
[2]"Molecular cloning of human brain glutamate/aspartate transporter II."
Shashidharan P., Wittenberg I., Plaitakis A.
Biochim. Biophys. Acta 1191:393-396(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Brain.
[3]"Cloning and characterization of a glutamate transporter cDNA from human brain and pancreas."
Manfras B.J., Rudert W.A., Trucco M., Boehm B.O.
Biochim. Biophys. Acta 1195:185-188(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Pancreas.
[4]"DL-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters."
Shimamoto K., Lebrun B., Yasuda-Kamatani Y., Sakaitani M., Shigeri Y., Yumoto N., Nakajima T.
Mol. Pharmacol. 53:195-201(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[5]"Cloning and characterization of the 3'-untranslated region of the human excitatory amino acid transporter 2 transcript."
Kim S.Y., Chao W., Choi S.Y., Volsky D.J.
J. Neurochem. 86:1458-1467(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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 3).
[7]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [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 (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[10]"A trimeric quaternary structure is conserved in bacterial and human glutamate transporters."
Gendreau S., Voswinkel S., Torres-Salazar D., Lang N., Heidtmann H., Detro-Dassen S., Schmalzing G., Hidalgo P., Fahlke C.
J. Biol. Chem. 279:39505-39512(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: QUATERNARY STRUCTURE.
[11]"Exon-skipping splice variants of excitatory amino acid transporter-2 (EAAT2) form heteromeric complexes with full-length EAAT2."
Gebhardt F.M., Mitrovic A.D., Gilbert D.F., Vandenberg R.J., Lynch J.W., Dodd P.R.
J. Biol. Chem. 285:31313-31324(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORM 3), SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U03505 mRNA. Translation: AAA50429.1.
U01824 mRNA. Translation: AAA18900.1.
Z32517 mRNA. Translation: CAA83532.1.
D85884 mRNA. Translation: BAA28706.1.
AY066021 mRNA. Translation: AAL57716.1.
AK298769 mRNA. Translation: BAG60911.1.
AL133330, AC090625 Genomic DNA. Translation: CAM28291.1.
CH471064 Genomic DNA. Translation: EAW68143.1.
BC132768 mRNA. Translation: AAI32769.1.
CCDSCCDS31459.1. [P43004-1]
CCDS55756.1. [P43004-2]
PIRI37426.
I38432.
RefSeqNP_001182657.1. NM_001195728.2. [P43004-2]
NP_001239581.1. NM_001252652.1. [P43004-2]
NP_004162.2. NM_004171.3. [P43004-1]
UniGeneHs.502338.

3D structure databases

ProteinModelPortalP43004.
SMRP43004. Positions 46-493.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112397. 3 interactions.
IntActP43004. 2 interactions.
STRING9606.ENSP00000278379.

Chemistry

BindingDBP43004.
ChEMBLCHEMBL4973.
DrugBankDB00142. L-Glutamic Acid.
GuidetoPHARMACOLOGY869.

Protein family/group databases

TCDB2.A.23.2.7. the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.

PTM databases

PhosphoSiteP43004.

Polymorphism databases

DMDM3041668.

Proteomic databases

PaxDbP43004.
PRIDEP43004.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000278379; ENSP00000278379; ENSG00000110436. [P43004-1]
ENST00000395750; ENSP00000379099; ENSG00000110436. [P43004-2]
ENST00000395753; ENSP00000379102; ENSG00000110436. [P43004-2]
ENST00000606205; ENSP00000476124; ENSG00000110436.
GeneID6506.
KEGGhsa:6506.
UCSCuc001mwd.3. human. [P43004-1]

Organism-specific databases

CTD6506.
GeneCardsGC11M035272.
HGNCHGNC:10940. SLC1A2.
HPACAB002574.
HPA009172.
MIM600300. gene.
neXtProtNX_P43004.
PharmGKBPA35827.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1301.
HOVERGENHBG000080.
InParanoidP43004.
KOK05613.
OMAFIAFGIC.
OrthoDBEOG7RV9G2.
PhylomeDBP43004.
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

ArrayExpressP43004.
BgeeP43004.
CleanExHS_SLC1A2.
GenevestigatorP43004.

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

ChiTaRSSLC1A2. human.
GeneWikiSLC1A2.
GenomeRNAi6506.
NextBio25297.
PMAP-CutDBP43004.
PROP43004.
SOURCESearch...

Entry information

Entry nameEAA2_HUMAN
AccessionPrimary (citable) accession number: P43004
Secondary accession number(s): B4DQE9 expand/collapse secondary AC list , Q14417, Q541G6, U3KQQ4
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: July 15, 1998
Last modified: July 9, 2014
This is version 130 of the entry and version 2 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 chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM