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Protein

Excitatory amino acid transporter 2

Gene

SLC1A2

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

ReactomeiREACT_12591. Glutamate Neurotransmitter Release Cycle.
REACT_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 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:10940. SLC1A2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4444CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei45 – 6420HelicalSequence AnalysisAdd
BLAST
Transmembranei88 – 10821HelicalSequence AnalysisAdd
BLAST
Transmembranei121 – 14222HelicalSequence AnalysisAdd
BLAST
Topological domaini143 – 23997ExtracellularSequence AnalysisAdd
BLAST
Transmembranei240 – 25920HelicalSequence AnalysisAdd
BLAST
Transmembranei280 – 30122HelicalSequence AnalysisAdd
BLAST
Transmembranei317 – 33923HelicalSequence AnalysisAdd
BLAST
Transmembranei406 – 43025HelicalSequence AnalysisAdd
BLAST
Transmembranei437 – 45923HelicalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • axolemma Source: Ensembl
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35827.

Polymorphism and mutation databases

BioMutaiSLC1A2.
DMDMi3041668.

PTM / Processingi

Molecule processing

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

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi38 – 381S-palmitoyl cysteineBy similarity
Glycosylationi206 – 2061N-linked (GlcNAc...)Sequence Analysis
Glycosylationi216 – 2161N-linked (GlcNAc...)Sequence Analysis
Modified residuei539 – 5391PhosphotyrosineBy 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

BgeeiP43004.
CleanExiHS_SLC1A2.
ExpressionAtlasiP43004. baseline and differential.
GenevestigatoriP43004.

Organism-specific databases

HPAiCAB002574.
HPA009172.

Interactioni

Subunit structurei

Homotrimer. Isoform 3 can oligomerize with isoform 1. Interacts with AJUBA (By similarity).By similarity

Binary interactionsi

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

Protein-protein interaction databases

BioGridi112397. 4 interactions.
IntActiP43004. 2 interactions.
STRINGi9606.ENSP00000278379.

Structurei

3D structure databases

ProteinModelPortaliP43004.
SMRiP43004. Positions 46-493.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1301.
GeneTreeiENSGT00760000119117.
HOVERGENiHBG000080.
InParanoidiP43004.
KOiK05613.
OMAiMICFYIT.
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. AlignAdd to basket

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

        10         20         30         40         50
MASTEGANNM PKQVEVRMHD SHLGSEEPKH RHLGLRLCDK LGKNLLLTLT
60 70 80 90 100
VFGVILGAVC GGLLRLASPI HPDVVMLIAF PGDILMRMLK MLILPLIISS
110 120 130 140 150
LITGLSGLDA KASGRLGTRA MVYYMSTTII AAVLGVILVL AIHPGNPKLK
160 170 180 190 200
KQLGPGKKND EVSSLDAFLD LIRNLFPENL VQACFQQIQT VTKKVLVAPP
210 220 230 240 250
PDEEANATSA VVSLLNETVT EVPEETKMVI KKGLEFKDGM NVLGLIGFFI
260 270 280 290 300
AFGIAMGKMG DQAKLMVDFF NILNEIVMKL VIMIMWYSPL GIACLICGKI
310 320 330 340 350
IAIKDLEVVA RQLGMYMVTV IIGLIIHGGI FLPLIYFVVT RKNPFSFFAG
360 370 380 390 400
IFQAWITALG TASSAGTLPV TFRCLEENLG IDKRVTRFVL PVGATINMDG
410 420 430 440 450
TALYEAVAAI FIAQMNGVVL DGGQIVTVSL TATLASVGAA SIPSAGLVTM
460 470 480 490 500
LLILTAVGLP TEDISLLVAV DWLLDRMRTS VNVVGDSFGA GIVYHLSKSE
510 520 530 540 550
LDTIDSQHRV HEDIEMTKTQ SIYDDMKNHR ESNSNQCVYA AHNSVIVDEC
560 570
KVTLAANGKS ADCSVEEEPW KREK
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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti7 – 71A → T in BAG60911 (PubMed:14702039).Curated
Sequence conflicti19 – 191H → P in AAA50429 (PubMed:7521911).Curated
Sequence conflicti27 – 271E → G in CAA83532 (PubMed:7522567).Curated
Sequence conflicti50 – 501T → Q in AAA18900 (PubMed:8172925).Curated
Sequence conflicti58 – 581A → S in AAA18900 (PubMed:8172925).Curated
Sequence conflicti141 – 1411A → G in CAA83532 (PubMed:7522567).Curated
Sequence conflicti155 – 1551P → A in CAA83532 (PubMed:7522567).Curated
Sequence conflicti211 – 2111V → E in AAA50429 (PubMed:7521911).Curated
Sequence conflicti253 – 2553GIA → AIP in CAA83532 (PubMed:7522567).Curated
Sequence conflicti263 – 28927AKLMV…MWYSP → GQADGGFLQHFERDCNEVSD HDHVVLS in CAA83532 (PubMed:7522567).CuratedAdd
BLAST
Sequence conflicti347 – 3471F → L in AAA50429 (PubMed:7521911).Curated
Sequence conflicti539 – 5391Y → F in CAA83532 (PubMed:7522567).Curated
Sequence conflicti556 – 5561A → G in CAA83532 (PubMed:7522567).Curated
Sequence conflicti563 – 5653CSV → RVL in CAA83532 (PubMed:7522567).Curated
Sequence conflicti570 – 5701W → G in CAA83532 (PubMed:7522567).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 99Missing in isoform 2. 1 PublicationVSP_037152
Alternative sequencei553 – 57422TLAAN…WKREK → HFPFMDIETCI in isoform 3. 1 PublicationVSP_054934Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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. [P43004-3]
GeneIDi6506.
KEGGihsa:6506.
UCSCiuc001mwd.3. human. [P43004-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliP43004.
SMRiP43004. Positions 46-493.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112397. 4 interactions.
IntActiP43004. 2 interactions.
STRINGi9606.ENSP00000278379.

Chemistry

BindingDBiP43004.
ChEMBLiCHEMBL4973.
GuidetoPHARMACOLOGYi869.

Protein family/group databases

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

PTM databases

PhosphoSiteiP43004.

Polymorphism and mutation databases

BioMutaiSLC1A2.
DMDMi3041668.

Proteomic databases

PaxDbiP43004.
PRIDEiP43004.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi6506.
GeneCardsiGC11M035272.
HGNCiHGNC:10940. SLC1A2.
HPAiCAB002574.
HPA009172.
MIMi600300. gene.
neXtProtiNX_P43004.
PharmGKBiPA35827.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG1301.
GeneTreeiENSGT00760000119117.
HOVERGENiHBG000080.
InParanoidiP43004.
KOiK05613.
OMAiMICFYIT.
OrthoDBiEOG7RV9G2.
PhylomeDBiP43004.
TreeFamiTF315206.

Enzyme and pathway databases

ReactomeiREACT_12591. Glutamate Neurotransmitter Release Cycle.
REACT_13639. Astrocytic Glutamate-Glutamine Uptake And Metabolism.
REACT_19397. Transport of inorganic cations/anions and amino acids/oligopeptides.

Miscellaneous databases

ChiTaRSiSLC1A2. human.
GeneWikiiSLC1A2.
GenomeRNAii6506.
NextBioi25297.
PMAP-CutDBP43004.
PROiP43004.
SOURCEiSearch...

Gene expression databases

BgeeiP43004.
CleanExiHS_SLC1A2.
ExpressionAtlasiP43004. baseline and differential.
GenevestigatoriP43004.

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]
ProtoNetiSearch...

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: May 27, 2015
This is version 138 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

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 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.