Details of Protein

General Information of Protein (ID: PRT01195)
Name Excitatory amino acid transporter 3 (SLC1A1)
Synonyms   Click to Show/Hide Synonyms of This Protein
Excitatory amino-acid carrier 1; Neuronal and epithelial glutamate transporter; Sodium-dependent glutamate/aspartate transporter 3; Solute carrier family 1 member 1; SLC1A1; EAAC1; EAAT3
Gene Name SLC1A1 Gene ID
6505
UniProt ID
P43005
Family Dicarboxylate/amino acid:cation symporter (DAACS)
TC Number   TC: 2.A.23.2.3  (Click to Show/Hide the Complete TC Tree)
The Dicarboxylate/Amino Acid:Cation (Na+ or H+) Symporter (DAACS) Family
.
TC: 2.A.23.2.3
  Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Function) of This Protein
Sequence
MGKPARKGCEWKRFLKNNWVLLSTVAAVVLGITTGVLVREHSNLSTLEKFYFAFPGEILM
RMLKLIILPLIISSMITGVAALDSNVSGKIGLRAVVYYFCTTLIAVILGIVLVVSIKPGV
TQKVGEIARTGSTPEVSTVDAMLDLIRNMFPENLVQACFQQYKTKREEVKPPSDPEMNMT
EESFTAVMTTAISKNKTKEYKIVGMYSDGINVLGLIVFCLVFGLVIGKMGEKGQILVDFF
NALSDATMKIVQIIMCYMPLGILFLIAGKIIEVEDWEIFRKLGLYMATVLTGLAIHSIVI
LPLIYFIVVRKNPFRFAMGMAQALLTALMISSSSATLPVTFRCAEENNQVDKRITRFVLP
VGATINMDGTALYEAVAAVFIAQLNDLDLGIGQIITISITATSASIGAAGVPQAGLVTMV
IVLSAVGLPAEDVTLIIAVDWLLDRFRTMVNVLGDAFGTGIVEKLSKKELEQMDVSSEVN
IVNPFALESTILDNEDSDTKKSYVNGGFAVDKSDTISFTQTSQF
Structure
6S3Q
Function Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate. Can also transport L-cysteine. 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. Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport. Plays an important role in L-glutamate and L-aspartate reabsorption in renal tubuli. 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. Contributes to glutathione biosynthesis and protection against oxidative stress via its role in L-glutamate and L-cysteine transport. Negatively regulated by ARL6IP5.
Regulatory Network
Full List of Metabolite(s) Regulated by This Protein
      Organic acids and derivatives
            Aspartic acid Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Overexpression of SLC1A1
                      Induced Change Aspartic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Motor neuron disease [ICD-11: 8B60]
                      Details It is reported that overexpression of SLC1A1 leads to the decrease of aspartic acid levels compared with control group.
            Cysteine Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Mutation (p.I395del) of SLC1A1
                      Induced Change Cysteine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Nephropathic cystinosis [ICD-11: 5C60]
                      Details It is reported that mutation (p.I395del) of SLC1A1 leads to the decrease of cysteine levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Mutation (p.R445W) of SLC1A1
                      Induced Change Cysteine concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Nephropathic cystinosis [ICD-11: 5C60]
                      Details It is reported that mutation (p.R445W) of SLC1A1 leads to the decrease of cysteine levels compared with control group.
            D-Aspartic acid Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Overexpression of SLC1A1
                      Induced Change D-Aspartic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Motor neuron disease [ICD-11: 8B60]
                      Details It is reported that overexpression of SLC1A1 leads to the decrease of D-aspartic acid levels compared with control group.
            DL-Glutamate Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [3]
                      Introduced Variation Overexpression of SLC1A1
                      Induced Change DL-Glutamate concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC1A1 leads to the increase of DL-Glutamate levels compared with control group.
            Glutamic acid Click to Show/Hide the Full List of Regulating Pair(s):   7 Pair(s)
               Detailed Information Metabo  Info click to show the details of this metabolite
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Mutation (p.I395del) of SLC1A1
                      Induced Change Glutamic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Nephropathic cystinosis [ICD-11: 5C60]
                      Details It is reported that mutation (p.I395del) of SLC1A1 leads to the decrease of glutamic acid levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [2]
                      Introduced Variation Mutation (p.R445W) of SLC1A1
                      Induced Change Glutamic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Nephropathic cystinosis [ICD-11: 5C60]
                      Details It is reported that mutation (p.R445W) of SLC1A1 leads to the decrease of glutamic acid levels compared with control group.
               Regulating Pair (3) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Overexpression of SLC1A1
                      Induced Change Glutamic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Motor neuron disease [ICD-11: 8B60]
                      Details It is reported that overexpression of SLC1A1 leads to the decrease of glutamic acid levels compared with control group.
               Regulating Pair (4) Experim Info click to show the details of experiment for validating this pair [4]
                      Introduced Variation Overexpression of SLC1A1
                      Induced Change Glutamic acid concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that overexpression of SLC1A1 leads to the increase of glutamic acid levels compared with control group.
               Regulating Pair (5) Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation Inhibition (DL-threo-beta-hydroxyaspartic acid (TBHA)) of SLC1A1
                      Induced Change Glutamic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that inhibition of SLC1A1 leads to the decrease of glutamic acid levels compared with control group.
               Regulating Pair (6) Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation Inhibition (L-serine-O-sulfate (SOS)) of SLC1A1
                      Induced Change Glutamic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that inhibition of SLC1A1 leads to the decrease of glutamic acid levels compared with control group.
               Regulating Pair (7) Experim Info click to show the details of experiment for validating this pair [5]
                      Introduced Variation Inhibition (L-trans-pyrrolidine-2,4-dicar-boxylic acid (PDC)) of SLC1A1
                      Induced Change Glutamic acid concentration: decrease
                      Summary Introduced Variation         Induced Change 
                      Disease Status Healthy individual
                      Details It is reported that inhibition of SLC1A1 leads to the decrease of glutamic acid levels compared with control group.
References
1 Primary structure and functional characterization of a high-affinity glutamate transporter. Nature. 1992 Dec 3;360(6403):467-71.
2 Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. J Clin Invest. 2011 Jan;121(1):446-53.
3 Caveolin-1 Sensitivity of Excitatory Amino Acid Transporters EAAT1, EAAT2, EAAT3, and EAAT4. J Membr Biol. 2016 Jun;249(3):239-49.
4 Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4155-60.
5 Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. J Neurosci. 1994 Sep;14(9):5559-69.

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