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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
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Genomic context

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See SLC1A6 in Genome Data Viewer
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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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

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