Property Summary

NCBI Gene PubMed Count 79
PubMed Score 522.49
PubTator Score 247.77

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (6)

Disease Target Count Z-score Confidence
Episodic ataxia 17 0.0 5.0
Disease Target Count
Epilepsy 346
Episodic ataxia, type 6 1
Disease Target Count
Episodic ataxia 6 1

Expression

  Differential Expression (25)

Disease log2 FC p
Rheumatoid Arthritis 1.200 4.9e-02
malignant mesothelioma 3.800 1.4e-09
ependymoma 3.100 1.1e-02
oligodendroglioma 2.200 2.1e-02
glioblastoma 1.700 4.4e-04
group 4 medulloblastoma -3.900 2.4e-11
cystic fibrosis 1.347 6.2e-05
atypical teratoid / rhabdoid tumor -2.300 4.1e-03
medulloblastoma, large-cell -3.600 1.4e-06
primitive neuroectodermal tumor -1.800 1.1e-02
intraductal papillary-mucinous adenoma (... -2.000 7.7e-04
intraductal papillary-mucinous carcinoma... -2.200 6.7e-04
intraductal papillary-mucinous neoplasm ... -1.500 2.9e-02
lung cancer -2.300 3.5e-05
fibroadenoma -2.100 4.0e-02
pediatric high grade glioma 1.200 4.7e-03
pilocytic astrocytoma -1.200 5.0e-06
subependymal giant cell astrocytoma -1.623 4.4e-02
invasive ductal carcinoma 1.405 4.3e-05
lung carcinoma -1.700 2.5e-08
Pick disease 1.100 8.1e-03
ductal carcinoma in situ -1.100 2.1e-02
ovarian cancer 2.000 1.7e-04
pituitary cancer -1.100 1.2e-03
Down syndrome 1.100 1.3e-02

Protein-protein Interaction (4)

Gene RIF (60)

PMID Text
26233565 SPAK and OSR1 are powerful negative regulators of the excitatory glutamate transporters EAAT1 and EAAT2.
26203187 data provide additional insights into the mechanism by which substrates gate the anion conductance in EAATs and suggest that in EAAT1, Arg-388 is a critical element for the structural coupling between the substrate translocation and the gating mechanisms
26057049 There was no association between pyramidal cell EAAT1 splice variant expression and schizophrenia.
25789968 discovering compounds that can enhance EAAT1 expression and activity may be a novel strategy for therapeutic treatment of glaucoma.
25660734 EAAT1 polymorphism which is involved in the Regulation of extracellular glutamate concentrations, influences Cognitive performances with a detrimental effect of T/T homozygosis.
25391854 Results showed that EAAT2 levels were significantly decreased in the essential tremor cerebellar cortex, in contrast to similar levels of EAAT1 levels between essential tremor cases and controls
25064059 Results describe EAAT1 and EAAT2 labeling in the prefrontal cortex in human postmortem control brains at the light and electron microscopic level
25036385 the delivered miR-124 increased the expression of the glutamate transporters, EAAT1 in NPCs and EAAT2 in both NPCs and astrocytes.
24332449 Its dysregulation may contribute to the pathology and possibly affect the onset of fragile X-associated tremor/ataxia syndrome.
23913256 Plasma membrane EAAT1 (and NCX1)are both involved in glutamate-induced ATP synthesis.
23706640 The results of this study showed that the expression of The membrane transporters SLC1A2 and SLC1A3 was diminished in the major depressive disorder group compared to controls.
23415275 Major depressive disorder is associated with unhealthy astrocytes in the noradrenergic Locus Coeruleus, characterized here by a reduction in astrocyte glutamate transporter expression.
23356950 Decreased expression of EAAT1 protein remodels glutamate neurotransmission in the superior temporal gyrus in schizophrenia.
23107647 Episodic ataxia type 6 represents the first human disease found to be associated with altered function of excitatory amino acid transporter anion channels.
22706862 EAAT-1 expression was found in 91% of choroid plexus tumors and was absent in endolymphatic sac tumors.
22569537 Letter: report expression of dishevelled-3 and EAAT1 and glutamine metabolism in malignant pleural mesothelioma.
22424243 Increased SLC1A3 expression in the cerebellum of elderly schizophrenia patients indicates facilitated transport and may result in reduced glutamate neurotransmission.
22292083 The accessibility in the external part of the TM5 of the glutamate transporter EAAT1 is conformationally sensitive during the transport cycle.
22252783 Close functional similarities of the GLAST/EAAT-1 promoter regions in man and rat exist which point to a species-specific function of the GLAST/EAAT-1 3'-UTR in constitutive and regulated GLAST/EAAT-1 expression.
21876140 A series of single cysteine substitutions in the helical hairpin HP2 of excitatory amino acid transporter 1 form intersubunit disulfide cross-links within the trimer.
21732909 water and urea permeation properties of wild-type EAAT1 and two mutant transporters were measured to identify which permeation pathway facilitates the movement of these molecules
21711518 findings suggest that allelic variability in SLC1A2/3, 5-HTR1B and NTRK2 may be relevant to the underlying diathesis for suicidal acts.
21707071 SLC2A1/GLUT1, SLC1A3/EAAT1, and SLC1A2/EAAT2 were the main SLC proteins whereas ABCG2/BCRP, ABCB1/MDR1, ABCA2 and ABCA8 were the main ABC quantified in isolated brain microvessels
21528001 There is no association between SLC1A3 and normal tension glaucoma (NTG), suggesting that the SLC1A3 gene may not be an associated factor in NTG pathogenesis.
21233784 These results indicate that E219D is a functional SLC1A3 variant that is presented in a small number of individuals with Tourette syndrome.
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
19913121 Observational study of gene-disease association. (HuGE Navigator)
19736351 Observational study of gene-disease association. (HuGE Navigator)
19352218 Observational study of gene-disease association. (HuGE Navigator)
19338517 The expression of EAAT-1 and EAAT-2 was reduced to approximately 40% and 25%, respectively, in CA1 of the hippocampus in intractable temporal lobe epilepsy.
19283393 immunoreactivity for EAAT-1, but not EAAT-2, distinguishes neoplastic choroid plexus (CP) from non-neoplastic CP and might be of help in making a diagnosis especially in well differentiated CP tissue
19156168 Clinical trial of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
19139306 We broadened the clinical spectrum associated with SLC1A3 mutations to include milder manifestations of EA without seizures or alternating hemiplegia. The severity of EA6 symptoms is related to the extent of glutamate transporter dysfunction.
19086053 Observational study of gene-disease association. (HuGE Navigator)
18678877 analysis of the importance of Leu-303 or its counterpart Leu-391 in human EAAT1 (hEAAT1)
18657127 increased expression in the prefrontal cortex of chronic alcoholics
18454440 Observational study of gene-disease association. (HuGE Navigator)
18446307 No pathogenic mutation were identified in SLC1A3.
18081024 Observational study of gene-disease association. (HuGE Navigator)
17676873 Mutations in transmembrane domains 5 and 7 of the human excitatory amino acid transporter 1 affect the substrate-activated anion channel
17627080 We documented for the first time the expression of the mGluR5 and EAAT1 in MG-63 cells, as well as the ability of dexamethasone to upregulate the expression of the mGluR5 and EAAT1 in the MG-63 cells.
17581948 Continued expression of GLAST by neural progenitor cells in the transgenic mouse brain raises the possibility that GLAST may have an unanticipated role in regulating their behavior.
17316900 Activity of GLAST directs FXYD2 protein/gamma subunit to the cell surface, that leads to the activation of the astroglial sodium pump.
17221839 Observational study of gene-disease association. (HuGE Navigator)
17221839 SLC1A3 is unlikely to be a major susceptibility gene for schizophrenia in the Japanese population.
16877378 Rearrangements in the tertiary structure of the EAAT1 translocation pore during transport provide constraints for modeling the structural dynamics associated with transport.
16516348 the activity of glutamate transporter GLAST/EAAT1 can effectively regulate the cell surface expression of glutamine/neutral amino acid transporter ASCT2 in human fetal astrocytes
16116111 Our data show that a heterozygous mutation in EAAT1 can lead to decreased glutamate uptake, which can contribute to neuronal hyperexcitability to cause seizures, hemiplegia, and episodic ataxia.
16061389 enhanced expression of glutamate transporters in multiple sclerosis constitutes a regulatory response of glial cells to toxic levels of glutamate in the CNS during inflammation and neurodegeneration
16042756 EAAT1ex9skip splice variant is a negative regulator of full-length EAAT1 function in the human brain
15950021 Genetic variation in SLC1A3 may contribute to susceptibility to ADHD.
15718040 EAAT1 parameters were mutually correlated (p<0.01) and correlations were shown with dementia severity (p<0.05 MMSE-expression, p<0.005 MMSE-mRNA).
15535133 Only activated macrophages/microglia (AMM) expressed EAAT-1. Proportion of AMM expressing EAAT-1 did not correlate with severity of neuronal apoptosis, spongiosis, astrocytosis, microgliosis, or PrP deposition, but only with disease duration.
15135231 data show specific localization of glutamate transporters EAAT1, EAAT2 and EAAT3 in the human placenta during development
14749132 We observed decreased glutamate uptake V(max), without modification of transporter affinity, in aging, which could be linked to the selective decrease of EAAT1 expression and mRNA. Moreover, in AD patients we found a further EAAT1 reduction.
14713304 Transcriptional regulation of human excitatory amino acid transporter 1 (EAAT1): cloning of the EAAT1 promoter and characterization of its basal and inducible activity in human astrocytes.
12911626 To test whether Nedd4-2, SGK1, SGK3 and protein kinase B regulate EAAT1, cRNA encoding EAAT1 was injected into Xenopus oocytes with or without injection of Nedd4-2, constitutively active[CA] S422DSGK1, inactive K127NSGK1, SGK3 and/or CA T308D,S473DPKB
12769187 Data show that excitatory amino acid transporter (EAAT)-1 was expressed by activated macrophages/microglia in all HIV-infected cases but not in HIV-negative controls.
11826152 EAAT1 was strongly expressed in a subset of cortical pyramidal neurons in dementia cases showing Alzheimer-type pathology. In addition, tau (which is a marker of neurofibrillary pathology) colocalized to those same pyramidal cells that expressed EAAT1
11792462 Dose-dependent modulation of EAAT1-mediated aspartate transport by benzodiazepines suggests a role of glial as well as neuronal transporters in drug action.

AA Sequence

MTKSNGEEPKMGGRMERFQQGVRKRTLLAKKKVQNITKEDVKSYLFRNAFVLLTVTAVIVGTILGFTLRP      1 - 70
YRMSYREVKYFSFPGELLMRMLQMLVLPLIISSLVTGMAALDSKASGKMGMRAVVYYMTTTIIAVVIGII     71 - 140
IVIIIHPGKGTKENMHREGKIVRVTAADAFLDLIRNMFPPNLVEACFKQFKTNYEKRSFKVPIQANETLV    141 - 210
GAVINNVSEAMETLTRITEELVPVPGSVNGVNALGLVVFSMCFGFVIGNMKEQGQALREFFDSLNEAIMR    211 - 280
LVAVIMWYAPVGILFLIAGKIVEMEDMGVIGGQLAMYTVTVIVGLLIHAVIVLPLLYFLVTRKNPWVFIG    281 - 350
GLLQALITALGTSSSSATLPITFKCLEENNGVDKRVTRFVLPVGATINMDGTALYEALAAIFIAQVNNFE    351 - 420
LNFGQIITISITATAASIGAAGIPQAGLVTMVIVLTSVGLPTDDITLIIAVDWFLDRLRTTTNVLGDSLG    421 - 490
AGIVEHLSRHELKNRDVEMGNSVIEENEMKKPYQLIAQDNETEKPIDSETKM                      491 - 542
//

Text Mined References (83)

PMID Year Title
26233565 2015 Down-Regulation of Excitatory Amino Acid Transporters EAAT1 and EAAT2 by the Kinases SPAK and OSR1.
26203187 2015 A Mutation in Transmembrane Domain 7 (TM7) of Excitatory Amino Acid Transporters Disrupts the Substrate-dependent Gating of the Intrinsic Anion Conductance and Drives the Channel into a Constitutively Open State.
26057049 2015 Glutamate transporter splice variant expression in an enriched pyramidal cell population in schizophrenia.
25789968 2015 Arundic acid attenuates retinal ganglion cell death by increasing glutamate/aspartate transporter expression in a model of normal tension glaucoma.
25660734 2015 Glutamate EAAT1 transporter genetic variants influence cognitive deficits in bipolar disorder.
25391854 2014 Decreased EAAT2 protein expression in the essential tremor cerebellar cortex.
25064059 2014 Localization of excitatory amino acid transporters EAAT1 and EAAT2 in human postmortem cortex: a light and electron microscopic study.
25036385 2014 Mesenchymal stem cells deliver exogenous miRNAs to neural cells and induce their differentiation and glutamate transporter expression.
24332449 2014 Reduced excitatory amino acid transporter 1 and metabotropic glutamate receptor 5 expression in the cerebellum of fragile X mental retardation gene 1 premutation carriers with fragile X-associated tremor/ataxia syndrome.
23913256 2013 Glutamate-induced ATP synthesis: relationship between plasma membrane Na+/Ca2+ exchanger and excitatory amino acid transporters in brain and heart cell models.
23706640 2013 Glutamate transporters: a key piece in the glutamate puzzle of major depressive disorder.
23415275 2013 Gene expression deficits in pontine locus coeruleus astrocytes in men with major depressive disorder.
23356950 2013 Abnormal expression of glutamate transporters in temporal lobe areas in elderly patients with schizophrenia.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23107647 2012 A point mutation associated with episodic ataxia 6 increases glutamate transporter anion currents.
22814378 2012 N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
22706862 2012 Diagnostic value of EAAT-1 and Kir7.1 for distinguishing endolymphatic sac tumors from choroid plexus tumors.
22569537 2012 The expression of Dishevelled-3 and glutamine metabolism in malignant pleural mesothelioma.
22424243 2013 Gene expression of glutamate transporters SLC1A1, SLC1A3 and SLC1A6 in the cerebellar subregions of elderly schizophrenia patients and effects of antipsychotic treatment.
22292083 2012 The accessibility in the external part of the TM5 of the glutamate transporter EAAT1 is conformationally sensitive during the transport cycle.
22252783 2012 Transcriptional regulation of the GLAST/EAAT-1 gene in rat and man.
22026960 2012 A new splice variant of the glutamate-aspartate transporter: cloning and immunolocalization of GLAST1c in rat, pig and human brains.
22020285 2011 Image-based genome-wide siRNA screen identifies selective autophagy factors.
21876140 2011 Large collective motions regulate the functional properties of glutamate transporter trimers.
21732909 2011 Water and urea permeation pathways of the human excitatory amino acid transporter EAAT1.
21711518 2011 Risk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B &NTRK2 polymorphisms.
21707071 2011 Transcriptomic and quantitative proteomic analysis of transporters and drug metabolizing enzymes in freshly isolated human brain microvessels.
21528001 2011 Investigation of the association between SLC1A3 gene polymorphisms and normal tension glaucoma.
21233784 2011 Genetic and functional studies of a missense variant in a glutamate transporter, SLC1A3, in Tourette syndrome.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19736351 2009 Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation.
19352218 2009 Candidate gene analysis in an on-going genome-wide association study of attention-deficit hyperactivity disorder: suggestive association signals in ADRA1A.
19338517 2009 Excitatory amino acid transporters EAAT-1 and EAAT-2 in temporal lobe and hippocampus in intractable temporal lobe epilepsy.
19283393 2009 Expression of EAAT-1 distinguishes choroid plexus tumors from normal and reactive choroid plexus epithelium.
19156168 2009 Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis.
19139306 2009 Episodic ataxia associated with EAAT1 mutation C186S affecting glutamate reuptake.
19086053 2009 Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment.
18678877 2008 Time-resolved mechanism of extracellular gate opening and substrate binding in a glutamate transporter.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18657127 2008 Impact of alcohol abuse on protein expression of midkine and excitatory amino acid transporter 1 in the human prefrontal cortex.
18454440 2009 Chromosome 5 and Gilles de la Tourette syndrome: Linkage in a large pedigree and association study of six candidates in the region.
18446307 2008 Episodic ataxia: SLC1A3 and CACNB4 do not explain the apparent genetic heterogeneity.
18081024 2008 Association study for genes at chromosome 5p13-q11 in attention deficit hyperactivity disorder.
17676873 2007 Mutations in transmembrane domains 5 and 7 of the human excitatory amino acid transporter 1 affect the substrate-activated anion channel.
17627080 Regulation of the mGluR5, EAAT1 and GS expression by glucocorticoids in MG-63 osteoblast-like osteosarcoma cells.
17581948 2007 Variations in promoter activity reveal a differential expression and physiology of glutamate transporters by glia in the developing and mature CNS.
17316900 2007 Glutamate transporter GLAST/EAAT1 directs cell surface expression of FXYD2/gamma subunit of Na, K-ATPase in human fetal astrocytes.
17221839 2007 Association study of polymorphisms in the glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 with schizophrenia.
16877378 2006 Structural rearrangements at the translocation pore of the human glutamate transporter, EAAT1.
16516348 High-affinity glutamate transporter GLAST/EAAT1 regulates cell surface expression of glutamine/neutral amino acid transporter ASCT2 in human fetal astrocytes.
16116111 2005 Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures.
16061389 2006 Increased expression and function of glutamate transporters in multiple sclerosis.
16042756 2005 A novel alternative splicing form of excitatory amino acid transporter 1 is a negative regulator of glutamate uptake.
15950021 2005 A family based study implicates solute carrier family 1-member 3 (SLC1A3) gene in attention-deficit/hyperactivity disorder.
15718040 2005 Fibroblast glutamate transport in aging and in AD: correlations with disease severity.
15535133 2004 Expression of excitatory amino acid transporter-1 (EAAT-1) in brain macrophages and microglia of patients with prion diseases.
15372022 2004 The DNA sequence and comparative analysis of human chromosome 5.
15135231 2004 Distribution of glutamate transporters in the human placenta.
14749132 2004 Glutamate transporters in platelets: EAAT1 decrease in aging and in Alzheimer's disease.
14713304 2003 Transcriptional regulation of human excitatory amino acid transporter 1 (EAAT1): cloning of the EAAT1 promoter and characterization of its basal and inducible activity in human astrocytes.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12957496 2003 Regulation of glial glutamate transporter expression by growth factors.
12911626 2003 Regulation of the glutamate transporter EAAT1 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid-inducible kinase isoforms SGK1/3 and protein kinase B.
12769187 2003 Expression of excitatory amino acid transporter-1 in brain macrophages and microglia of HIV-infected patients. A neuroprotective role for activated microglia?
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11792462 2002 Benzodiazepines differently modulate EAAT1/GLAST and EAAT2/GLT1 glutamate transporters expressed in CHO cells.
11752470 2001 Sulfhydryl modification of V449C in the glutamate transporter EAAT1 abolishes substrate transport but not the substrate-gated anion conductance.
10915646 2000 EAAT1 is involved in transport of L-glutamate during differentiation of the Caco-2 cell line.
10864655 2000 Human T-cell lymphotropic virus type 1-infected T lymphocytes impair catabolism and uptake of glutamate by astrocytes via Tax-1 and tumor necrosis factor alpha.
10594060 1999 Compromised glutamate transport in human glioma cells: reduction-mislocalization of sodium-dependent glutamate transporters and enhanced activity of cystine-glutamate exchange.
10570036 1999 Differentiation of substrate and nonsubstrate inhibitors of the high-affinity, sodium-dependent glutamate transporters.
10519046 1999 Properties of excitatory amino acid transport in the human U373 astrocytoma cell line.
9110174 1997 Large-scale concatenation cDNA sequencing.
8647279 1996 Human high affinity, Na(+)-dependent L-glutamate/L-aspartate transporter GLAST-1 (EAAT-1): gene structure and localization to chromosome 5p11-p12.
8619474 1996 A "double adaptor" method for improved shotgun library construction.
8218410 1993 Cloning and characterization of a glutamate transporter cDNA from human cerebellum.
8123008 1994 Cloning and expression of a human glutamate transporter.
8001975 1994 The mouse and human excitatory amino acid transporter gene (EAAT1) maps to mouse chromosome 15 and a region of syntenic homology on human chromosome 5.
7859077 1994 Neuron-specific human glutamate transporter: molecular cloning, characterization and expression in human brain.
7698014 1995 Localization of the gene (SLC1A3) encoding human glutamate transporter (GluT-1) to 5p13 by fluorescence in situ hybridization.
7584044 1994 Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1.
7521911 1994 Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex.