Tchem SLC1A1 Excitatory amino acid transporter 3

Protein Summary

Description

Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:7914198, PubMed:7521911, PubMed:8857541, PubMed:26690923, PubMed:21123949). Can also transport L-cysteine (PubMed:21123949). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion (PubMed:7521911, PubMed:8857541, PubMed:26690923). Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport (PubMed:8857541, PubMed:26690923). Plays an important role in L-glutamate and L-aspartate reabsorption in renal tubuli (PubMed:21123949). Plays a redundant role in the rapid removal of released glutamate from the synaptic cleft, which is essential for terminating the postsynaptic action of glutamate (By similarity). Negatively regulated by ARL6IP5 (By similarity). This gene encodes a member of the high-affinity glutamate transporters that play an essential role in transporting glutamate across plasma membranes. In brain, these transporters are crucial in terminating the postsynaptic action of the neurotransmitter glutamate, and in maintaining extracellular glutamate concentrations below neurotoxic levels. This transporter also transports aspartate, and mutations in this gene are thought to cause dicarboxylicamino aciduria, also known as glutamate-aspartate transport defect. [provided by RefSeq, Mar 2010]

Uniprot Accession IDs

• P43005
• O75587
• Q5VZ24
• Q8N199
• Q9UEW2

Gene Name

• SLC1A1

Ensembl ID

• ENST00000262352
• ENSP00000262352
• ENSG00000106688

Symbol

• EAAC1
• EAAT3
• DCBXA
• EAAC1
• EAAT3
• SCZD18

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	1
PubMedID	0.97
transcription factor perturbation	0.84
disease perturbation	0.79
virus perturbation	0.79

Protein Classes

PANTHER Classes

Protein / Transporter / Cation Transporter / Excitatory Amino Acid Transporter 3

DTO Classes

Protein / Transporter / Slc Superfamily Of Solute Carriers / Slc1 Family Of Amino Acid Transporters / Glutamate Transporter Subfamily / Excitatory Amino Acid Transporter 3

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 501.19   (req: < 5)

Gene RIFs: 74   (req: <= 3)

Antibodies: 329   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 501.19   (req: >= 5)

Gene RIFs: 74   (req: > 3)

Antibodies: 329   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 20

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 29

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (5)

RESOLUTE

RESOLUTE is a public-private partnership with the goal of escalating research on solute carriers (SLCs) and to establish SLCs as a tractable target class for medical research and development.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (1)

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1 – 1 of 1

glutamic acid

SLC1A1Tchem Transporter

AGONIST pKi : 7.4

Active Ligands (29)

Explore Active Ligands

1 – 10 of 29

DL-TBOA

SLC1A1Tchem Transporter

pKi : 5.5

[³H]ETB-TBOA

SLC1A1Tchem Transporter

pKd : 7.6

NBI-59159

SLC1A1Tchem Transporter

pIC50 : 7.1

2-Amino-N-(7-fluoro-9H-fluoren-2-yl)-succinamic acid

SLC1A1Tchem Transporter

pIC50 : 7.3

CHEMBL4177507

SLC1A1Tchem Transporter

pIC50 : 7.93

CHEMBL4176482

SLC1A1Tchem Transporter

pIC50 : 7.97

CHEMBL4176427

SLC1A1Tchem Transporter

pIC50 : 8.9

CHEMBL1257519

SLC1A1Tchem Transporter

pIC50 : 8.45

CHEMBL4165811

SLC1A1Tchem Transporter

pIC50 : 7.68

CHEMBL2113112

SLC1A1Tchem Transporter

pIC50 : 7

Protein-Protein Interactions (139)

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1 – 10 of 139

• See Interactions on String-DB

NUMBL

Tbio

Novelty:  0.01383607

p_int:  0.999998807

p_ni:  0.000001157

p_wrong:  3.6e-8

Score:  0.195

Data Source:  BioPlex,STRINGDB

CC2D1A

Tbio

Novelty:  0.01970021

p_int:  0.99999014

p_ni:  0.000005717

p_wrong:  0.000004143

Data Source:  BioPlex

FMC1

Tbio

Novelty:  0.06702205

p_int:  0.999638614

p_ni:  0.000162539

p_wrong:  0.000198846

Data Source:  BioPlex

SLC9A3R2

Tbio

Family:  Transporter

Novelty:  0.01401705

p_int:  0.999492664

p_ni:  0.000466191

p_wrong:  0.000041145

Score:  0.26

Data Source:  BioPlex,STRINGDB

SNX3

Tbio

Novelty:  0.02703152

p_int:  0.999330553

p_ni:  0.000669433

p_wrong:  1.5e-8

Score:  0.159

Data Source:  BioPlex,STRINGDB

INPPL1

Tchem

Family:  Enzyme

Novelty:  0.00634126

p_int:  0.998360738

p_ni:  0.001639255

p_wrong:  7e-9

Data Source:  BioPlex

GOLGA7

Tbio

Novelty:  0.17108842

p_int:  0.998311616

p_ni:  0.001649344

p_wrong:  0.00003904

Score:  0.177

Data Source:  BioPlex,STRINGDB

ORMDL3

Tbio

Novelty:  0.00958976

p_int:  0.99757306

p_ni:  0.000006192

p_wrong:  0.002420748

Data Source:  BioPlex

NDFIP1

Tbio

Novelty:  0.04496467

p_int:  0.995288793

p_ni:  0.004711207

Data Source:  BioPlex

NRN1

Tbio

Novelty:  0.01198116

p_int:  0.992843289

p_ni:  0.007153985

p_wrong:  0.000002726

Data Source:  BioPlex

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (16)

Reactome (11)

KEGG (3)

PathwayCommons (2)

Defective SLC1A1 is implicated in schizophrenia 18 (SCZD18) and dicarboxylic aminoaciduria (DCBXA) (R-HSA-5619067)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Defective SLC1A1 is implicated in schizophrenia 18 (SCZD18) and dicarboxylic aminoaciduria (DCBXA)	1 targets	R-HSA-5619067
Reactome	Disease	1105 targets	R-HSA-1643685
Reactome	Disorders of transmembrane transporters	178 targets	R-HSA-5619115
Reactome	Glutamate Neurotransmitter Release Cycle	24 targets	R-HSA-210500
Reactome	Neuronal System	398 targets	R-HSA-112316

Name	Explore in Pharos	Explore in Source
Defective SLC1A1 is implicated in schizophrenia 18 (SCZD18) and dicarboxylic aminoaciduria (DCBXA)	1 targets	R-HSA-5619067
Disease	1105 targets	R-HSA-1643685
Disorders of transmembrane transporters	178 targets	R-HSA-5619115
Glutamate Neurotransmitter Release Cycle	24 targets	R-HSA-210500
Neuronal System	398 targets	R-HSA-112316

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (25)

Functions (8)

Components (5)

Processes (12)

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1 – 8 of 8

GO Term	Evidence	Assigned by
cysteine transmembrane transporter activity	Inferred from Direct Assay (IDA)	UniProtKB
glutamate:sodium symporter activity	Inferred from Direct Assay (IDA)	UniProtKB
high-affinity glutamate transmembrane transporter activity	Inferred from Direct Assay (IDA)	UniProtKB
L-glutamate transmembrane transporter activity	Inferred from Direct Assay (IDA)	UniProtKB
chloride transmembrane transporter activity	Inferred from Mutant Phenotype (IMP)	UniProtKB
amino acid transmembrane transporter activity	Traceable Author Statement (TAS)	Reactome
glutamate binding	Inferred from Electronic Annotation (IEA)	Ensembl
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations (null)

No disease associations found

GWAS Traits (7)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean platelet volume	EFO_0004584	2	2	2		78.2
platelet crit	EFO_0007985	1	1	1		51.4
neutrophil count	EFO_0004833	1	1	1		37.6
response to antipsychotic drug	GO_0097332	1	1	0	3.4	33.1
hip circumference	EFO_0005093	1	1	1		21.5

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean platelet volume	EFO_0004584	2		78.2
platelet crit	EFO_0007985	1		51.4
neutrophil count	EFO_0004833	1		37.6
response to antipsychotic drug	GO_0097332	0	3.4	33.1
hip circumference	EFO_0005093	1		21.5

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UniProt Keyword Find Similar Targets

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Amino-acid transport
Cell membrane
Chloride
Complete proteome
Disease mutation
Glycoprotein
Membrane
Metal-binding
Phosphoprotein
Polymorphism

GWAS Trait Find Similar Targets

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erythrocyte count
hip circumference
mean platelet volume
neutrophil count
platelet crit
response to antipsychotic drug
response to risperidone

MGI Phenotype Find Similar Targets

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adipose tissue phenotype
behavior/neurological phenotype
cellular phenotype
homeostasis/metabolism phenotype
nervous system phenotype
renal/urinary system phenotype
vision/eye phenotype

IDG Resources

No IDG generated resources found

Orthologs (14)

1 – 5 of 14

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	solute carrier family 1 member 1	VGNC:8928	464974
Macaque	solute carrier family 1 member 1		694947
Mouse	solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, system Xag), member 1	MGI:105083	20510
Rat	solute carrier family 1 member 1	RGD:3696	25550
Dog	solute carrier family 1 member 1	VGNC:46261	403751

Species	Name	OMA	EggNOG	Inparanoid
Chimp	solute carrier family 1 member 1
Macaque	solute carrier family 1 member 1
Mouse	solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, system Xag), member 1
Rat	solute carrier family 1 member 1
Dog	solute carrier family 1 member 1

Publication Statistics

PubMed Score 501.19

PubMed score by year

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PubTator Score 226.23

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Related Publications

Text Mined References (98)

GeneRif Annotations (74)

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PMID	Year	Title