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    SLC1A6 solute carrier family 1 member 6 [ Homo sapiens (human) ]

    Gene ID: 6511, updated on 7-Apr-2024

    Summary

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    Official Symbol
    SLC1A6provided by HGNC
    Official Full Name
    solute carrier family 1 member 6provided by HGNC
    Primary source
    HGNC:HGNC:10944
    See related
    Ensembl:ENSG00000105143 MIM:600637; AllianceGenome:HGNC:10944
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    EAAT4
    Summary
    Predicted to enable high-affinity glutamate transmembrane transporter activity. Involved in neurotransmitter uptake. Located in intermediate filament cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Biased expression in testis (RPKM 7.7), brain (RPKM 2.7) and 1 other tissue See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    19p13.12
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (14950033..15010643, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (15074841..15135544, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (15060845..15121455, complement)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene olfactory receptor family 7 subfamily A member 15 pseudogene Neighboring gene olfactory receptor family 7 subfamily C member 2 Neighboring gene Sharpr-MPRA regulatory region 13248 Neighboring gene tektin like 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10264 Neighboring gene caspase 14

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. A conserved aspartate determines pore properties of anion channels associated with excitatory amino acid transporter 4 (EAAT4). Kovermann P, et al. J Biol Chem, 2010 Jul 30. PMID 20519505, Free PMC Article
    2. Niflumic acid modulates uncoupled substrate-gated conductances in the human glutamate transporter EAAT4. Poulsen MV, et al. J Physiol, 2001 Jul 1. PMID 11432999, Free PMC Article
    3. Neuronal glutamate transporters regulate glial excitatory transmission. Tsai MC, et al. J Neurosci, 2012 Feb 1. PMID 22302796, Free PMC Article
    4. Substrate-dependent gating of anion channels associated with excitatory amino acid transporter 4. Machtens JP, et al. J Biol Chem, 2011 Jul 8. PMID 21572047, Free PMC Article
    5. EAAT4 phosphorylation at the SGK1 consensus site is required for transport modulation by the kinase. Rajamanickam J, et al. J Neurochem, 2007 Aug. PMID 17442044

    See all (20) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Lithium-sensitive GSK3ss is a powerful regulator of excitatory amino acid transporters EAAT3 and EAAT4.
      Title: Up-Regulation of Excitatory Amino Acid Transporters EAAT3 and EAAT4 by Lithium Sensitive Glycogen Synthase Kinase GSK3ß.
    2. Decreased SLC1A6 expression in neuregulin 1 risk variant may be an adaptive effect to restore glutamate signalling in schizophrenia patients.
      Title: Gene expression of glutamate transporters SLC1A1, SLC1A3 and SLC1A6 in the cerebellar subregions of elderly schizophrenia patients and effects of antipsychotic treatment.
    3. A twofold difference in functional EAAT4 levels is sufficient to alter signaling to Bergman glia in reporter mice.
      Title: Neuronal glutamate transporters regulate glial excitatory transmission.
    4. strate-dependent gating of anion channels associated with excitatory amino acid transporter 4.
      Title: Substrate-dependent gating of anion channels associated with excitatory amino acid transporter 4.
    5. a conserved aspartate determines pore properties of anion channels associated with excitatory amino acid transporter 4 (EAAT4)
      Title: A conserved aspartate determines pore properties of anion channels associated with excitatory amino acid transporter 4 (EAAT4).
    6. Clinical trial of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis.
    7. Observational study of gene-disease association. (HuGE Navigator)
      Title: L-type voltage-dependent calcium channel alpha subunit 1C is a novel candidate gene associated with secondary hyperparathyroidism: an application of haplotype-based analysis for multiple linked single nucleotide polymorphisms.
    8. conclusion, maximal glutamate transport modulation by SGK1 is accomplished by direct EAAT4 stimulation and to a lesser extent by inhibition of intrinsic Nedd4-2.
      Title: EAAT4 phosphorylation at the SGK1 consensus site is required for transport modulation by the kinase.
    9. At least one susceptibility locus for schizophrenia may be located within or nearby SLC1A6.
      Title: Association study of polymorphisms in the glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 with schizophrenia.
    10. Independent, rather than cooperative anion conductance gating significantly alters predictions of the influence that EAAT4-mediated anion currents will have on synaptic transmission at low glutamate concentrations.
      Title: The glutamate-activated anion conductance in excitatory amino acid transporters is gated independently by the individual subunits.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC33092, MGC43671

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables L-aspartate transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables L-glutamate transmembrane transporter activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables L-glutamate transmembrane transporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables glutamate:sodium symporter activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables glutamate:sodium symporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables high-affinity L-glutamate transmembrane transporter activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables high-affinity L-glutamate transmembrane transporter activity TAS
    Traceable Author Statement
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables neutral L-amino acid transmembrane transporter activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in L-aspartate import across plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in L-glutamate import across plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in L-glutamate import across plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in L-glutamate transmembrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in aspartate transmembrane transport TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in chemical synaptic transmission TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in establishment of localization in cell IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in monoatomic ion transport TAS
    Traceable Author Statement
    more info
    		  
    involved_in neurotransmitter transport TAS
    Traceable Author Statement
    more info
    		  
    involved_in neurotransmitter uptake IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in neurotransmitter uptake IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in neurotransmitter uptake NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in neutral amino acid transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of membrane potential IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in Golgi apparatus IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in intermediate filament cytoskeleton IDA
    Inferred from Direct Assay
    more info
    		  
    located_in membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    part_of membrane protein complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		  
    located_in plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in presynaptic membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    excitatory amino acid transporter 4
    Names
    sodium-dependent glutamate/aspartate transporter
    solute carrier family 1 (high affinity aspartate/glutamate transporter), member 6

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001272087.2 → NP_001259016.1  excitatory amino acid transporter 4 isoform 1

      See identical proteins and their annotated locations for NP_001259016.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript. Variants 1 and 3 encode the same isoform (1).
      Source sequence(s)
      AC004659, BC028721, BC040604, BI829415, DA059558
      Consensus CDS
      CCDS62578.1
      UniProtKB/Swiss-Prot
      P48664
      Related
      ENSP00000471781.1, ENST00000598504.5
      Conserved Domains (1) summary
      cl00573
      Location:58 → 312
      SDF; Sodium:dicarboxylate symporter family

    2. NM_001272088.2 → NP_001259017.1  excitatory amino acid transporter 4 isoform 1

      See identical proteins and their annotated locations for NP_001259017.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1 and 3 encode the same isoform (1).
      Source sequence(s)
      AC004659, BC028721, DA059558, DR004792
      Consensus CDS
      CCDS62578.1
      UniProtKB/Swiss-Prot
      P48664
      Related
      ENSP00000446175.1, ENST00000544886.6
      Conserved Domains (1) summary
      cl00573
      Location:58 → 312
      SDF; Sodium:dicarboxylate symporter family

    3. NM_001384669.1 → NP_001371598.1  excitatory amino acid transporter 4 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC004659
      Consensus CDS
      CCDS12321.1
      UniProtKB/Swiss-Prot
      P48664, Q8N753
      UniProtKB/TrEMBL
      M0R063
      Related
      ENSP00000221742.3, ENST00000221742.7
      Conserved Domains (1) summary
      pfam00375
      Location:58 → 522
      SDF; Sodium:dicarboxylate symporter family

    4. NM_001384670.1 → NP_001371599.1  excitatory amino acid transporter 4 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC004659
      Consensus CDS
      CCDS62578.1
      Conserved Domains (1) summary
      cl00573
      Location:58 → 312
      SDF; Sodium:dicarboxylate symporter family

    5. NM_001384671.1 → NP_001371600.1  excitatory amino acid transporter 4 isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC004659
      Conserved Domains (1) summary
      cl00573
      Location:58 → 117
      SDF; Sodium:dicarboxylate symporter family

    6. NM_005071.3 → NP_005062.1  excitatory amino acid transporter 4 isoform 2

      See identical proteins and their annotated locations for NP_005062.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and its transcription extends past a splice site that is used in variant 1, resulting in a novel 3' coding region and 3' UTR compared to variant 1. It encodes isoform 2 which is longer and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC004659
      Consensus CDS
      CCDS12321.1
      UniProtKB/Swiss-Prot
      P48664, Q8N753
      UniProtKB/TrEMBL
      M0R063
      Related
      ENSP00000472133.2, ENST00000594383.2
      Conserved Domains (1) summary
      pfam00375
      Location:58 → 522
      SDF; Sodium:dicarboxylate symporter family

    RNA

    1. NR_073589.2 RNA Sequence

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) uses an alternate 5' and 3' exon structure, compared to variant 1. This variant is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with translation of the longest ORF; translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AK302380, DA200776, DB027852, HY352099, U18244
      Related
      ENST00000430939.6

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      14950033..15010643 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047439234.1 → XP_047295190.1  excitatory amino acid transporter 4 isoform X1

      UniProtKB/Swiss-Prot
      P48664, Q8N753
      Related
      ENSP00000471038.1, ENST00000600144.5

    2. XM_047439233.1 → XP_047295189.1  excitatory amino acid transporter 4 isoform X1

      UniProtKB/Swiss-Prot
      P48664, Q8N753

    3. XM_017027152.3 → XP_016882641.1  excitatory amino acid transporter 4 isoform X1

      UniProtKB/Swiss-Prot
      P48664, Q8N753
      UniProtKB/TrEMBL
      M0R063
      Conserved Domains (1) summary
      pfam00375
      Location:58 → 522
      SDF; Sodium:dicarboxylate symporter family

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      15074841..15135544 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054321792.1 → XP_054177767.1  excitatory amino acid transporter 4 isoform X1

      UniProtKB/Swiss-Prot
      P48664, Q8N753

    2. XM_054321791.1 → XP_054177766.1  excitatory amino acid transporter 4 isoform X1

      UniProtKB/Swiss-Prot
      P48664, Q8N753

    3. XM_054321790.1 → XP_054177765.1  excitatory amino acid transporter 4 isoform X1

      UniProtKB/Swiss-Prot
      P48664, Q8N753
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P48664.1 GenPept UniProtKB/Swiss-Prot:P48664

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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