Chrna4 cholinergic receptor, nicotinic, alpha polypeptide 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Chrna4provided by MGI
Official Full Name: cholinergic receptor, nicotinic, alpha polypeptide 4provided by MGI
Primary source: MGI:MGI:87888
See related: Ensembl:ENSMUSG00000027577 AllianceGenome:MGI:87888
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: EBN1; Acra4; ENFL1; Acra-4
Summary: Enables acetylcholine-gated cation-selective channel activity. Contributes to acetylcholine receptor activity. Involved in regulation of synaptic vesicle exocytosis. Acts upstream of or within several processes, including behavioral response to nicotine; chemical synaptic transmission; and regulation of dopamine secretion. Located in dopaminergic synapse and external side of plasma membrane. Part of acetylcholine-gated channel complex. Is integral component of presynaptic membrane. Is expressed in several structures, including alimentary system; genitourinary system; integumental system; nervous system; and sensory organ. Human ortholog(s) of this gene implicated in autosomal dominant nocturnal frontal lobe epilepsy 1 and nicotine dependence. Orthologous to human CHRNA4 (cholinergic receptor nicotinic alpha 4 subunit). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in kidney adult (RPKM 15.0), whole brain E14.5 (RPKM 7.5) and 10 other tissues See more
Orthologs: human all
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Genomic context

Location:: 2 H4; 2 103.54 cM

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	2	NC_000068.8 (180664104..180685339, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	2	NC_000068.7 (181022311..181043579, complement)

Chromosome 2 - NC_000068.8 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?

Mice lacking alpha4 nicotinic acetylcholine receptors are protected against alcohol-associated liver injury.
Title: Mice lacking α4 nicotinic acetylcholine receptors are protected against alcohol-associated liver injury.
alpha4beta2 nicotinic acetylcholine receptors intrinsically influence body weight in mice.
Title: α4β2 nicotinic acetylcholine receptors intrinsically influence body weight in mice.
Following alpha4beta2 nAChR stimulation, activated PKCbetaII translocated to the plasma membrane to induce clathrin-mediated endocytosis of D3R, resulting in downregulation and signal inhibition.
Title: α4β2 nicotinic acetylcholine receptor downregulates D(3) dopamine receptor expression through protein kinase C activation.
Serine residues S336, S470 and S530 in Chrna4 protein have a brain region dependent modulatory role on surface alpha4beta2 nicotinic receptor expression.
Title: Serine residues in the α4 nicotinic acetylcholine receptor subunit regulate surface α4β2(*) receptor expression and clustering.
The numbers of nAChR alpha4 immuno-positive cells and western blot levels were significally increased by 15-Hz auricular electrical stimulation in the hippocampal CA2 output cortex. The numbers of choline acetyltransferase (ChAT) - a key enzyme for biosynthesis of ACh - immuno-positive cells and western blot levels had no significant differences.
Title: Short-term auricular electrical stimulation rapidly elevated cortical blood flow and promoted the expression of nicotinic acetylcholine receptor α4 in the 2 vessel occlusion rats model.
Acetylcholine tone fine-tunes the firing properties of Dopamine (DA) neurons of the ventral tegmental area through beta2-containing (beta2*) nicotinic Acetylcholine receptors.
Title: Manipulating midbrain dopamine neurons and reward-related behaviors with light-controllable nicotinic acetylcholine receptors.
Data suggest that receptor complex assembly from Chrna4 and Chrnb2 on neuronal cell surface is up-regulated by nicotine; combined effects of increased assembly stoichiometry and preferential trafficking likely drive up-regulation of this receptor complex on neuronal cell surface upon nicotine exposure. (Chrna4 = a4 nicotinic receptor; Chrnb2 = b2 nicotinic receptor)
Title: Organelle-specific single-molecule imaging of α4β2 nicotinic receptors reveals the effect of nicotine on receptor assembly and cell-surface trafficking.
Results suggest that alpha4beta2( *) nAChRs can produce sustained regulation of inhibitory post-synaptic GABA currents, in fast-spiking layer V neurons of the mouse frontal area 2.
Title: α4β2(∗) nicotinic receptors stimulate GABA release onto fast-spiking cells in layer V of mouse prefrontal (Fr2) cortex.
Mice lacking alpha4 subunits in ventral midbrain consumed significantly more nicotine at the highest offered nicotine concentration compared to control mice.
Title: Altered nicotine reward-associated behavior following α4 nAChR subunit deletion in ventral midbrain.
Varenicline treatment may prevent scopolamine-induced memory disturbance by a molecular mechanism that may involve increased alpha4beta2 nAChR availability. Varenicline dose-dependently increased protein expression of both the alpha4 and beta2 subunit in cell cultures and brain tissues, respectively, but had no effect on mRNA expression; lack of change in mRNA expression suggests a still unknown post-transcriptional me...
Title: Effects of varenicline on alpha4-containing nicotinic acetylcholine receptor expression and cognitive performance in mice.

Submit: New GeneRIF Correction See all GeneRIFs (66)

Variation

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Alleles

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

Spontaneous (4) 1 citation
Targeted (14) 1 citation
Endonuclease-mediated (2)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH94428 (e-PCR)
- UniSTS:119676

Chrna4 (e-PCR), detects polymorphism
- UniSTS:506799

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables acetylcholine binding	ISO Inferred from Sequence Orthology more info
contributes_to acetylcholine receptor activity	IBA Inferred from Biological aspect of Ancestor more info
contributes_to acetylcholine receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables acetylcholine receptor activity	ISO Inferred from Sequence Orthology more info
enables acetylcholine-gated monoatomic cation-selective channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables acetylcholine-gated monoatomic cation-selective channel activity	IGI Inferred from Genetic Interaction more info	PubMed
enables acetylcholine-gated monoatomic cation-selective channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables acetylcholine-gated monoatomic cation-selective channel activity	ISO Inferred from Sequence Orthology more info
enables acetylcholine-gated monoatomic cation-selective channel activity	TAS Traceable Author Statement more info	PubMed
enables extracellular ligand-gated monoatomic ion channel activity	IEA Inferred from Electronic Annotation more info
contributes_to heterocyclic compound binding	ISO Inferred from Sequence Orthology more info
enables heterocyclic compound binding	ISO Inferred from Sequence Orthology more info
enables monoatomic ion channel activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info
enables quaternary ammonium group binding	ISO Inferred from Sequence Orthology more info
enables transmembrane signaling receptor activity	IEA Inferred from Electronic Annotation more info
enables transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within B cell activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA repair	ISO Inferred from Sequence Orthology more info
involved_in acetylcholine receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within acetylcholine receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within behavioral response to nicotine	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in behavioral response to nicotine	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within calcium ion transport	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cognition	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within exploration behavior	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within inhibitory postsynaptic potential	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within locomotory behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in membrane depolarization	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within membrane depolarization	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within membrane depolarization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in monoatomic ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within monoatomic ion transport	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within nervous system process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nervous system process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within neuronal action potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in presynaptic modulation of chemical synaptic transmission	IDA Inferred from Direct Assay more info	PubMed
involved_in presynaptic modulation of chemical synaptic transmission	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of dopamine secretion	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of membrane potential	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within respiratory gaseous exchange by respiratory system	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to acetylcholine	ISO Inferred from Sequence Orthology more info
involved_in response to hypoxia	ISO Inferred from Sequence Orthology more info
involved_in response to nicotine	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within response to nicotine	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within response to nicotine	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within response to nicotine	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to nicotine	ISO Inferred from Sequence Orthology more info
involved_in response to oxidative stress	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within sensory perception of pain	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within sensory perception of pain	TAS Traceable Author Statement more info	PubMed
involved_in signal transduction	ISO Inferred from Sequence Orthology more info
involved_in synaptic transmission, cholinergic	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within synaptic transmission, cholinergic	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within synaptic transmission, cholinergic	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synaptic transmission, cholinergic	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
part_of acetylcholine-gated channel complex	IBA Inferred from Biological aspect of Ancestor more info
part_of acetylcholine-gated channel complex	IDA Inferred from Direct Assay more info	PubMed
part_of acetylcholine-gated channel complex	IPI Inferred from Physical Interaction more info	PubMed
part_of acetylcholine-gated channel complex	ISO Inferred from Sequence Orthology more info
is_active_in cholinergic synapse	ISO Inferred from Sequence Orthology more info
located_in dendrite	ISO Inferred from Sequence Orthology more info
is_active_in dopaminergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in dopaminergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
located_in external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in neuron projection	IBA Inferred from Biological aspect of Ancestor more info
located_in neuronal cell body	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	IDA Inferred from Direct Assay more info	PubMed
located_in postsynaptic membrane	IEA Inferred from Electronic Annotation more info
is_active_in postsynaptic specialization membrane	ISO Inferred from Sequence Orthology more info
located_in presynapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in presynaptic membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in presynaptic membrane	IEP Inferred from Expression Pattern more info	PubMed
is_active_in presynaptic membrane	IMP Inferred from Mutant Phenotype more info	PubMed
is_active_in presynaptic membrane	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info
is_active_in synapse	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: neuronal acetylcholine receptor subunit alpha-4

Names: a4 nicotinic receptor; acetylcholine receptor alpha 4 neural; acetylcholine receptor, neuronal, nicotinic, alpha-4 subunit; alpha4 nAChR

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_001416868.1 → NP_001403797.1 neuronal acetylcholine receptor subunit alpha-4 isoform 2

Status: VALIDATED

Source sequence(s)

AL450341
NM_015730.6 → NP_056545.3 neuronal acetylcholine receptor subunit alpha-4 isoform 1 precursor

See identical proteins and their annotated locations for NP_056545.3

Status: VALIDATED

Source sequence(s)

AL450341

Consensus CDS

CCDS17192.1

UniProtKB/Swiss-Prot

O70174, Q8BHE9, Q8VI10, Q9ET51

UniProtKB/TrEMBL

B7ZBU7, Q53YK0

Related

ENSMUSP00000066338.8, ENSMUST00000067120.14

Conserved Domains (2) summary

pfam02931
Location:39 → 245

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:252 → 620

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region

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_000068.8 Reference GRCm39 C57BL/6J

Range

180664104..180685339 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_030246772.2 → XP_030102632.1 neuronal acetylcholine receptor subunit alpha-4 isoform X2

Conserved Domains (3) summary

cl28912
Location:1 → 66

LGIC_ECD; extracellular domain (ECD) of Cys-loop neurotransmitter-gated ion channels (also known as ligand-gated ion channel (LGIC))

pfam02932
Location:74 → 441

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region

pfam05350
Location:257 → 344

GSK-3_bind; Glycogen synthase kinase-3 binding