Slc1a6 solute carrier family 1 (high affinity aspartate/glutamate transporter), member 6 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Slc1a6provided by MGI
Official Full Name: solute carrier family 1 (high affinity aspartate/glutamate transporter), member 6provided by MGI
Primary source: MGI:MGI:1096331
See related: Ensembl:ENSMUSG00000005357 AllianceGenome:MGI:1096331
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: EAAT4
Summary: Enables L-glutamate transmembrane transporter activity. Acts upstream of or within L-glutamate transmembrane transport and regulation of membrane potential. Located in Golgi apparatus; glutamatergic synapse; and membrane. Is integral component of presynaptic membrane. Is expressed in central nervous system and retina. Orthologous to human SLC1A6 (solute carrier family 1 member 6). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in cerebellum adult (RPKM 37.6), CNS E18 (RPKM 8.8) and 5 other tissues See more
Orthologs: human all
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Genomic context

Location:: 10 C1; 10 39.72 cM

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	10	NC_000076.7 (78615923..78650659)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	10	NC_000076.6 (78780086..78814825)

Chromosome 10 - NC_000076.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Climbing Fiber-Mediated Spillover Transmission to Interneurons Is Regulated by EAAT4.
Title: Climbing Fiber-Mediated Spillover Transmission to Interneurons Is Regulated by EAAT4.
EAAT4 role in the spontaneous firing pattern and survival of Purkinje cells.
Title: Loss of cerebellar glutamate transporters EAAT4 and GLAST differentially affects the spontaneous firing pattern and survival of Purkinje cells.
Reduced Cerebellar EAAT4 Expression associated with loss of cerebellar Purkinje cells resluts in neurodegeneration and Niemann-Pick disease Type C1.
Title: Impact of Reduced Cerebellar EAAT Expression on Purkinje Cell Firing Pattern of NPC1-deficient Mice.
Overexpressed miR-128 downregulates the expression of AXIN1 but upregulates that of EAAT4 in dopamine neurons of Parkinson's disease mice.
Title: MicroRNA-128 Protects Dopamine Neurons from Apoptosis and Upregulates the Expression of Excitatory Amino Acid Transporter 4 in Parkinson's Disease by Binding to AXIN1.
Loss of EAAT4 accounts for the initial hyper-excitability of Purkinje cells lacking b-III spectrin and that loss of GLAST appears to work synergistically to worsen motor deficits. When levels of both EAAT4 and GLAST are compromised in b-III(-/-) mice, the proximal dendrites of Purkinje cells within the posterior cerebellum are the most vulnerable to degeneration.
Title: Posterior cerebellar Purkinje cells in an SCA5/SPARCA1 mouse model are especially vulnerable to the synergistic effect of loss of β-III spectrin and GLAST.
EAAT4 was downregulated due to the loss of Rheb1 in Purkinje cells; mTORC1 was downregulated and Akt was upregulated in Rheb1 cKO mice, suggesting that mTORC1 and Akt may be related to the downregulation of EAAT4; Rheb1 knockout decreased EAAT4 currents and slowed down the kinetics of AMPA currents; Rheb1 deficiency did not affect the morphology of Purkinje cell layer and the development of Purkinje cells
Title: Downregulation of Glutamate Transporter EAAT4 by Conditional Knockout of Rheb1 in Cerebellar Purkinje Cells.
Glutamate transporters EAAT4 and EAAT5 are expressed in vestibular hair cells and calyx endings.
Title: Glutamate transporters EAAT4 and EAAT5 are expressed in vestibular hair cells and calyx endings.
The role of EAAT4 in cortical glutamatergic transmission may be more important than previously thought.
Title: Quantitative analysis of EAAT4 promoter activity in neurons and astrocytes of mouse somatic sensory cortex.
Purkinje cell loss in the Inpp4a(wbl) mutant is due to glutamate excitotoxicity initiated by the climbing fiber, and that Eaat4 may exert a protective effect.
Title: Patterned neuroprotection in the Inpp4a(wbl) mutant mouse cerebellum correlates with the expression of Eaat4.
PF-evoked mGluR-EPSCs showed larger amplitude and faster rising kinetics in EAAT4-deficient mice than in the wild-type mice. EAAT4 is most closely involved in mGluR activation in PCs among the glutamate transporters.
Title: Facilitated activation of metabotropic glutamate receptors in cerebellar Purkinje cells in glutamate transporter EAAT4-deficient mice.

Submit: New GeneRIF Correction See all GeneRIFs (18)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (1) 1 citation
Endonuclease-mediated (3)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D83262 (e-PCR)
- UniSTS:180065

Slc1a6 (e-PCR), detects polymorphism
- UniSTS:547017

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables L-aspartate transmembrane transporter activity	ISO Inferred from Sequence Orthology more info
enables L-glutamate transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables L-glutamate transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables L-glutamate transmembrane transporter activity	ISO Inferred from Sequence Orthology more info
enables glutamate:sodium symporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables glutamate:sodium symporter activity	ISO Inferred from Sequence Orthology more info
enables high-affinity L-glutamate transmembrane transporter activity	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables monoatomic anion transmembrane transporter activity	ISO Inferred from Sequence Orthology more info
enables neutral L-amino acid transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables symporter activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in L-aspartate import across plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in L-glutamate import across plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in L-glutamate transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within L-glutamate transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in L-glutamate transmembrane transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within amino acid transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within establishment of localization in cell	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neurotransmitter uptake	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of membrane potential	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
located_in intermediate filament cytoskeleton	ISO Inferred from Sequence Orthology more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
part_of membrane protein complex	ISO Inferred from Sequence Orthology more info
is_active_in parallel fiber to Purkinje cell synapse	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
is_active_in postsynaptic membrane	ISO Inferred from Sequence Orthology more info
is_active_in presynaptic membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: excitatory amino acid transporter 4

Names: high-affinity neuronal glutamate transporter; sodium-dependent glutamate/aspartate transporter; solute carrier family 1, 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)

NM_001428830.1 → NP_001415759.1 excitatory amino acid transporter 4 isoform 1

Status: VALIDATED

Source sequence(s)

AC159747
NM_009200.4 → NP_033226.1 excitatory amino acid transporter 4 isoform 2

See identical proteins and their annotated locations for NP_033226.1

Status: VALIDATED

Source sequence(s)

AC159747

Consensus CDS

CCDS23970.1

UniProtKB/Swiss-Prot

O35544

UniProtKB/TrEMBL

B2RQX4, Q3TXM3

Related

ENSMUSP00000005490.9, ENSMUST00000005490.10

Conserved Domains (1) summary

pfam00375
Location:55 → 519

SDF; Sodium:dicarboxylate symporter family

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000076.7 Reference GRCm39 C57BL/6J

Range

78615923..78650659

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006513424.4 → XP_006513487.1 excitatory amino acid transporter 4 isoform X3

UniProtKB/TrEMBL

Q3TXM3

Conserved Domains (1) summary

pfam00375
Location:55 → 532

SDF; Sodium:dicarboxylate symporter family
XM_036155715.1 → XP_036011608.1 excitatory amino acid transporter 4 isoform X3

UniProtKB/TrEMBL

Q3TXM3

Conserved Domains (1) summary

pfam00375
Location:55 → 532

SDF; Sodium:dicarboxylate symporter family
XM_006513422.4 → XP_006513485.3 excitatory amino acid transporter 4 isoform X1

UniProtKB/TrEMBL

Q3TXM3

Conserved Domains (1) summary

pfam00375
Location:83 → 560

SDF; Sodium:dicarboxylate symporter family
XM_030244972.1 → XP_030100832.1 excitatory amino acid transporter 4 isoform X2

UniProtKB/TrEMBL

Q3TXM3

Conserved Domains (1) summary

pfam00375
Location:83 → 547

SDF; Sodium:dicarboxylate symporter family