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P43004

- EAA2_HUMAN

UniProt

P43004 - EAA2_HUMAN

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Protein
Excitatory amino acid transporter 2
Gene
SLC1A2, EAAT2, GLT1
Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. L-glutamate transmembrane transporter activity Source: BHF-UCL
  2. glutamate:sodium symporter activity Source: Ensembl
  3. protein binding Source: IntAct
  4. sodium:dicarboxylate symporter activity Source: InterPro

GO - Biological processi

  1. D-aspartate import Source: UniProtKB
  2. L-glutamate import Source: UniProtKB
  3. adult behavior Source: Ensembl
  4. cellular response to extracellular stimulus Source: Ensembl
  5. ion transport Source: Reactome
  6. multicellular organism growth Source: Ensembl
  7. multicellular organismal aging Source: Ensembl
  8. positive regulation of glucose import Source: Ensembl
  9. response to amino acid Source: Ensembl
  10. response to drug Source: Ensembl
  11. response to wounding Source: Ensembl
  12. synaptic transmission Source: ProtInc
  13. telencephalon development Source: Ensembl
  14. transmembrane transport Source: Reactome
  15. visual behavior Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Symport, Transport

Enzyme and pathway databases

ReactomeiREACT_13639. Astrocytic Glutamate-Glutamine Uptake And Metabolism.
REACT_19397. Transport of inorganic cations/anions and amino acids/oligopeptides.

Protein family/group databases

TCDBi2.A.23.2.7. the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:SLC1A2
Synonyms:EAAT2, GLT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:10940. SLC1A2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4444Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei45 – 6420Helical; Reviewed prediction
Add
BLAST
Transmembranei88 – 10821Helical; Reviewed prediction
Add
BLAST
Transmembranei121 – 14222Helical; Reviewed prediction
Add
BLAST
Topological domaini143 – 23997Extracellular Reviewed prediction
Add
BLAST
Transmembranei240 – 25920Helical; Reviewed prediction
Add
BLAST
Transmembranei280 – 30122Helical; Reviewed prediction
Add
BLAST
Transmembranei317 – 33923Helical; Reviewed prediction
Add
BLAST
Transmembranei406 – 43025Helical; Reviewed prediction
Add
BLAST
Transmembranei437 – 45923Helical; Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. axolemma Source: Ensembl
  2. integral component of membrane Source: UniProtKB-KW
  3. membrane Source: ProtInc
  4. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35827.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 574574Excitatory amino acid transporter 2
PRO_0000202061Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi38 – 381S-palmitoyl cysteine By similarity
Glycosylationi206 – 2061N-linked (GlcNAc...) Reviewed prediction
Glycosylationi216 – 2161N-linked (GlcNAc...) Reviewed prediction
Modified residuei539 – 5391Phosphotyrosine By similarity

Post-translational modificationi

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

Keywords - PTMi

Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiP43004.
PRIDEiP43004.

PTM databases

PhosphoSiteiP43004.

Miscellaneous databases

PMAP-CutDBP43004.

Expressioni

Gene expression databases

ArrayExpressiP43004.
BgeeiP43004.
CleanExiHS_SLC1A2.
GenevestigatoriP43004.

Organism-specific databases

HPAiCAB002574.
HPA009172.

Interactioni

Subunit structurei

Homotrimer. Isoform 3 can oligomerize with isoform 1. Interacts with AJUBA By similarity.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MAPTP106364EBI-3440986,EBI-366182

Protein-protein interaction databases

BioGridi112397. 3 interactions.
IntActiP43004. 2 interactions.
STRINGi9606.ENSP00000278379.

Structurei

3D structure databases

ProteinModelPortaliP43004.
SMRiP43004. Positions 46-493.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1301.
HOVERGENiHBG000080.
InParanoidiP43004.
KOiK05613.
OMAiFIAFGIC.
OrthoDBiEOG7RV9G2.
PhylomeDBiP43004.
TreeFamiTF315206.

Family and domain databases

Gene3Di1.10.3860.10. 2 hits.
InterProiIPR001991. Na-dicarboxylate_symporter.
IPR018107. Na-dicarboxylate_symporter_CS.
[Graphical view]
PANTHERiPTHR11958. PTHR11958. 1 hit.
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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P43004-1) [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

MASTEGANNM PKQVEVRMHD SHLGSEEPKH RHLGLRLCDK LGKNLLLTLT    50
VFGVILGAVC GGLLRLASPI HPDVVMLIAF PGDILMRMLK MLILPLIISS 100
LITGLSGLDA KASGRLGTRA MVYYMSTTII AAVLGVILVL AIHPGNPKLK 150
KQLGPGKKND EVSSLDAFLD LIRNLFPENL VQACFQQIQT VTKKVLVAPP 200
PDEEANATSA VVSLLNETVT EVPEETKMVI KKGLEFKDGM NVLGLIGFFI 250
AFGIAMGKMG DQAKLMVDFF NILNEIVMKL VIMIMWYSPL GIACLICGKI 300
IAIKDLEVVA RQLGMYMVTV IIGLIIHGGI FLPLIYFVVT RKNPFSFFAG 350
IFQAWITALG TASSAGTLPV TFRCLEENLG IDKRVTRFVL PVGATINMDG 400
TALYEAVAAI FIAQMNGVVL DGGQIVTVSL TATLASVGAA SIPSAGLVTM 450
LLILTAVGLP TEDISLLVAV DWLLDRMRTS VNVVGDSFGA GIVYHLSKSE 500
LDTIDSQHRV HEDIEMTKTQ SIYDDMKNHR ESNSNQCVYA AHNSVIVDEC 550
KVTLAANGKS ADCSVEEEPW KREK 574
Length:574
Mass (Da):62,104
Last modified:July 15, 1998 - v2
Checksum:iC8104E6727979435
GO
Isoform 2 (identifier: P43004-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: Missing.

Show »
Length:565
Mass (Da):61,228
Checksum:iA7286207F550252F
GO
Isoform 3 (identifier: P43004-3) [UniParc]FASTAAdd to Basket

Also known as: EEAT2b

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

Show »
Length:563
Mass (Da):61,008
Checksum:iC13903644ADD1802
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 99Missing in isoform 2.
VSP_037152
Alternative sequencei553 – 57422TLAAN…WKREK → HFPFMDIETCI in isoform 3.
VSP_054934Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti7 – 71A → T in BAG60911. 1 Publication
Sequence conflicti19 – 191H → P in AAA50429. 1 Publication
Sequence conflicti27 – 271E → G in CAA83532. 1 Publication
Sequence conflicti50 – 501T → Q in AAA18900. 1 Publication
Sequence conflicti58 – 581A → S in AAA18900. 1 Publication
Sequence conflicti141 – 1411A → G in CAA83532. 1 Publication
Sequence conflicti155 – 1551P → A in CAA83532. 1 Publication
Sequence conflicti211 – 2111V → E in AAA50429. 1 Publication
Sequence conflicti253 – 2553GIA → AIP in CAA83532. 1 Publication
Sequence conflicti263 – 28927AKLMV…MWYSP → GQADGGFLQHFERDCNEVSD HDHVVLS in CAA83532. 1 Publication
Add
BLAST
Sequence conflicti347 – 3471F → L in AAA50429. 1 Publication
Sequence conflicti539 – 5391Y → F in CAA83532. 1 Publication
Sequence conflicti556 – 5561A → G in CAA83532. 1 Publication
Sequence conflicti563 – 5653CSV → RVL in CAA83532. 1 Publication
Sequence conflicti570 – 5701W → G in CAA83532. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS31459.1. [P43004-1]
CCDS55756.1. [P43004-2]
PIRiI37426.
I38432.
RefSeqiNP_001182657.1. NM_001195728.2. [P43004-2]
NP_001239581.1. NM_001252652.1. [P43004-2]
NP_004162.2. NM_004171.3. [P43004-1]
UniGeneiHs.502338.

Genome annotation databases

EnsembliENST00000278379; ENSP00000278379; ENSG00000110436. [P43004-1]
ENST00000395750; ENSP00000379099; ENSG00000110436. [P43004-2]
ENST00000395753; ENSP00000379102; ENSG00000110436. [P43004-2]
ENST00000606205; ENSP00000476124; ENSG00000110436.
GeneIDi6506.
KEGGihsa:6506.
UCSCiuc001mwd.3. human. [P43004-1]

Polymorphism databases

DMDMi3041668.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS31459.1. [P43004-1 ]
CCDS55756.1. [P43004-2 ]
PIRi I37426.
I38432.
RefSeqi NP_001182657.1. NM_001195728.2. [P43004-2 ]
NP_001239581.1. NM_001252652.1. [P43004-2 ]
NP_004162.2. NM_004171.3. [P43004-1 ]
UniGenei Hs.502338.

3D structure databases

ProteinModelPortali P43004.
SMRi P43004. Positions 46-493.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112397. 3 interactions.
IntActi P43004. 2 interactions.
STRINGi 9606.ENSP00000278379.

Chemistry

BindingDBi P43004.
ChEMBLi CHEMBL4973.
DrugBanki DB00142. L-Glutamic Acid.
GuidetoPHARMACOLOGYi 869.

Protein family/group databases

TCDBi 2.A.23.2.7. the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family.

PTM databases

PhosphoSitei P43004.

Polymorphism databases

DMDMi 3041668.

Proteomic databases

PaxDbi P43004.
PRIDEi P43004.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000278379 ; ENSP00000278379 ; ENSG00000110436 . [P43004-1 ]
ENST00000395750 ; ENSP00000379099 ; ENSG00000110436 . [P43004-2 ]
ENST00000395753 ; ENSP00000379102 ; ENSG00000110436 . [P43004-2 ]
ENST00000606205 ; ENSP00000476124 ; ENSG00000110436 .
GeneIDi 6506.
KEGGi hsa:6506.
UCSCi uc001mwd.3. human. [P43004-1 ]

Organism-specific databases

CTDi 6506.
GeneCardsi GC11M035272.
HGNCi HGNC:10940. SLC1A2.
HPAi CAB002574.
HPA009172.
MIMi 600300. gene.
neXtProti NX_P43004.
PharmGKBi PA35827.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1301.
HOVERGENi HBG000080.
InParanoidi P43004.
KOi K05613.
OMAi FIAFGIC.
OrthoDBi EOG7RV9G2.
PhylomeDBi P43004.
TreeFami TF315206.

Enzyme and pathway databases

Reactomei REACT_13639. Astrocytic Glutamate-Glutamine Uptake And Metabolism.
REACT_19397. Transport of inorganic cations/anions and amino acids/oligopeptides.

Miscellaneous databases

ChiTaRSi SLC1A2. human.
GeneWikii SLC1A2.
GenomeRNAii 6506.
NextBioi 25297.
PMAP-CutDB P43004.
PROi P43004.
SOURCEi Search...

Gene expression databases

ArrayExpressi P43004.
Bgeei P43004.
CleanExi HS_SLC1A2.
Genevestigatori P43004.

Family and domain databases

Gene3Di 1.10.3860.10. 2 hits.
InterProi IPR001991. Na-dicarboxylate_symporter.
IPR018107. Na-dicarboxylate_symporter_CS.
[Graphical view ]
PANTHERi PTHR11958. PTHR11958. 1 hit.
Pfami PF00375. SDF. 1 hit.
[Graphical view ]
PRINTSi PR00173. EDTRNSPORT.
SUPFAMi SSF118215. SSF118215. 2 hits.
PROSITEi PS00713. NA_DICARBOXYL_SYMP_1. 1 hit.
PS00714. NA_DICARBOXYL_SYMP_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. 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.

Entry informationi

Entry nameiEAA2_HUMAN
AccessioniPrimary (citable) accession number: P43004
Secondary accession number(s): B4DQE9
, Q14417, Q541G6, U3KQQ4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: July 15, 1998
Last modified: September 3, 2014
This is version 131 of the entry and version 2 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 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi