Atxn3 ataxin 3 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Atxn3provided by MGI
Official Full Name: ataxin 3provided by MGI
Primary source: MGI:MGI:1099442
See related: Ensembl:ENSMUSG00000021189 AllianceGenome:MGI:1099442
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: Mjd; ATX3; MJD1; Sca3; ataxin-3; 2210008M02Rik
Summary: Enables cysteine-type deubiquitinase activity and ubiquitin protein ligase binding activity. Involved in cellular response to misfolded protein; monoubiquitinated protein deubiquitination; and proteolysis involved in protein catabolic process. Acts upstream of or within several processes, including cellular response to heat; exploration behavior; and ubiquitin-dependent protein catabolic process. Located in mitochondrial matrix; mitochondrial membrane; and nuclear inclusion body. Is expressed in several structures, including alimentary system; brain; hemolymphoid system gland; musculature; and testis. Used to study Machado-Joseph disease. Human ortholog(s) of this gene implicated in Machado-Joseph disease and late onset Parkinson's disease. Orthologous to human ATXN3 (ataxin 3). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Ubiquitous expression in testis adult (RPKM 13.9), bladder adult (RPKM 6.4) and 24 other tissues See more
Orthologs: human all
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Genomic context

Location:: 12 E; 12 51.32 cM

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	12	NC_000078.7 (101885160..101928139, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	12	NC_000078.6 (101918901..101959121, complement)

Chromosome 12 - NC_000078.7 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?

KPNB1 modulates the Machado-Joseph disease protein ataxin-3 through activation of the mitochondrial protease CLPP.
Title: KPNB1 modulates the Machado-Joseph disease protein ataxin-3 through activation of the mitochondrial protease CLPP.
A Novel SCA3 Knock-in Mouse Model Mimics the Human SCA3 Disease Phenotype Including Neuropathological, Behavioral, and Transcriptional Abnormalities Especially in Oligodendrocytes.
Title: A Novel SCA3 Knock-in Mouse Model Mimics the Human SCA3 Disease Phenotype Including Neuropathological, Behavioral, and Transcriptional Abnormalities Especially in Oligodendrocytes.
Ubiquilin-2 differentially regulates polyglutamine disease proteins.
Title: Ubiquilin-2 differentially regulates polyglutamine disease proteins.
ATXN3 positively regulates type I IFN antiviral response by deubiquitinating and stabilizing HDAC3
Title: ATXN3 Positively Regulates Type I IFN Antiviral Response by Deubiquitinating and Stabilizing HDAC3.
Loss of the Spinocerebellar Ataxia type 3 disease protein ATXN3 alters transcription of multiple signal transduction pathways
Title: Loss of the Spinocerebellar Ataxia type 3 disease protein ATXN3 alters transcription of multiple signal transduction pathways.
findings identify a novel molecular link between ATX-3 and p53-mediated cell death and provide an explanation for the direct involvement of p53 in SCA3 disease pathogenesis
Title: The Machado-Joseph Disease Deubiquitinase Ataxin-3 Regulates the Stability and Apoptotic Function of p53.
We show that chronic VPA treatment did not modify the ATXN3 inclusion load and astrogliosis in affected brain regions However, VPA chronic treatment was able to increase GRP78 protein levels at 30 weeks of age, one of its known neuroprotective effects
Title: Limited Effect of Chronic Valproic Acid Treatment in a Mouse Model of Machado-Joseph Disease.
work suggests that in Machado-Joseph disease, mutant ataxin-3 drives an abnormal reduction of ataxin-2 levels, which overactivates poly(A)-binding protein, increases translation of mutant ataxin-3 and other proteins and aggravates Machado-Joseph disease.
Title: Re-establishing ataxin-2 downregulates translation of mutant ataxin-3 and alleviates Machado-Joseph disease.
SCA3 knockin mice exhibit robust Atxn3 accumulation both in regions known to be affected in human disease; also display altered splicing of the mutant Atxn3 transcript that results in the formation of a previously described alternative ATXN3 transcript
Title: A knockin mouse model of spinocerebellar ataxia type 3 exhibits prominent aggregate pathology and aberrant splicing of the disease gene transcript.
Data support the importance of ATXN3 in neuronal cells and indicate that an expanded polyQ tract leads to a partial loss of the cellular function of ATXN3 that may be relevant to neurodegeneration.
Title: Dominant negative effect of polyglutamine expansion perturbs normal function of ataxin-3 in neuronal cells.

Submit: New GeneRIF Correction See all GeneRIFs (37)

Variation

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Alleles

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

Endonuclease-mediated (3) 1 citation
Gene trapped (2) 1 citation
Targeted (7) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AI463012 (e-PCR)
- UniSTS:164511

AV074322 (e-PCR)
- UniSTS:165840

AI647473 (e-PCR)
- UniSTS:180452

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATPase binding	ISO Inferred from Sequence Orthology more info
enables ATPase binding	ISS Inferred from Sequence or Structural Similarity more info
enables K48-linked deubiquitinase activity	ISO Inferred from Sequence Orthology more info
enables K48-linked deubiquitinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables K63-linked deubiquitinase activity	ISO Inferred from Sequence Orthology more info
enables K63-linked deubiquitinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables cysteine-type deubiquitinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables cysteine-type deubiquitinase activity	IDA Inferred from Direct Assay more info	PubMed
enables cysteine-type deubiquitinase activity	ISO Inferred from Sequence Orthology more info
contributes_to histone deacetylase activity	ISO Inferred from Sequence Orthology more info
enables histone deacetylase binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription corepressor binding	ISO Inferred from Sequence Orthology more info
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin protein ligase binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within actin cytoskeleton organization	ISO Inferred from Sequence Orthology more info
involved_in actin cytoskeleton organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to amino acid starvation	ISO Inferred from Sequence Orthology more info
involved_in cellular response to amino acid starvation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within cellular response to heat	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to misfolded protein	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within exploration behavior	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within intermediate filament cytoskeleton organization	ISO Inferred from Sequence Orthology more info
involved_in intermediate filament cytoskeleton organization	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within microtubule cytoskeleton organization	ISO Inferred from Sequence Orthology more info
involved_in microtubule cytoskeleton organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in monoubiquitinated protein deubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of TORC1 signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of TORC1 signaling	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of TORC1 signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of ERAD pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of ERAD pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein K48-linked deubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein K48-linked deubiquitination	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein K63-linked deubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein K63-linked deubiquitination	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein localization to cytosolic proteasome complex	ISO Inferred from Sequence Orthology more info
involved_in protein modification process	ISO Inferred from Sequence Orthology more info
involved_in protein quality control for misfolded or incompletely synthesized proteins	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein quality control for misfolded or incompletely synthesized proteins	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of cell-substrate adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of cell-substrate adhesion	ISO Inferred from Sequence Orthology more info
involved_in regulation of cell-substrate adhesion	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISS Inferred from Sequence or Structural Similarity more info
colocalizes_with endoplasmic reticulum membrane	ISO Inferred from Sequence Orthology more info
is_active_in lysosomal membrane	ISO Inferred from Sequence Orthology more info
is_active_in lysosomal membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in mitochondrial matrix	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial membrane	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear inclusion body	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear matrix	IEA Inferred from Electronic Annotation more info
located_in nucleolus	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: ataxin-3

Names: Machado-Joseph disease (spinocerebellar ataxia 3, olivopontocerebellar ataxia 3, autosomal dominant, ataxin 3) homolog; machado-Joseph disease protein 1 homolog

NP_001161386.1

EC 3.4.19.12

NP_083981.2

EC 3.4.19.12

XP_030102382.1

EC 3.4.19.12

XP_030102383.1

EC 3.4.19.12

XP_030102386.1

EC 3.4.19.12

XP_036013055.1

EC 3.4.19.12

XP_036013056.1

EC 3.4.19.12

XP_036013057.1

EC 3.4.19.12

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_001167914.1 → NP_001161386.1 ataxin-3 isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs at the 3' end compared to variant 1, resulting in an isoform (2) with a shorter C-terminus compared to isoform 1.

Source sequence(s)

BC049743, BC087880

Consensus CDS

CCDS49144.1

UniProtKB/TrEMBL

E9Q717, F6T5L3

Related

ENSMUSP00000125378.2, ENSMUST00000161011.8

Conserved Domains (2) summary

pfam02099
Location:9 → 163

Josephin

pfam16619
Location:264 → 291

SUIM_assoc; Unstructured region C-term to UIM in Ataxin3
NM_029705.3 → NP_083981.2 ataxin-3 isoform 1

See identical proteins and their annotated locations for NP_083981.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AK030842, BC049743, BQ174976, BX526801

Consensus CDS

CCDS26115.1

UniProtKB/Swiss-Prot

Q9CVD2

UniProtKB/TrEMBL

Q546X9

Related

ENSMUSP00000021606.6, ENSMUST00000021606.12

Conserved Domains (2) summary

pfam02099
Location:9 → 163

Josephin

pfam16619
Location:264 → 322

SUIM_assoc; Unstructured region C-term to UIM in Ataxin3

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_000078.7 Reference GRCm39 C57BL/6J

Range

101885160..101928139 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_030246522.2 → XP_030102382.1 ataxin-3 isoform X1

Conserved Domains (2) summary

pfam02099
Location:9 → 162

Josephin

pfam16619
Location:263 → 321

SUIM_assoc; Unstructured region C-term to UIM in Ataxin3
XM_030246523.1 → XP_030102383.1 ataxin-3 isoform X3

Conserved Domains (2) summary

pfam02099
Location:1 → 116

Josephin

pfam16619
Location:217 → 275

SUIM_assoc; Unstructured region C-term to UIM in Ataxin3
XM_036157163.1 → XP_036013056.1 ataxin-3 isoform X4

Conserved Domains (1) summary

pfam16619
Location:85 → 143

SUIM_assoc; Unstructured region C-term to UIM in Ataxin3
XM_036157164.1 → XP_036013057.1 ataxin-3 isoform X4

Conserved Domains (1) summary

pfam16619
Location:85 → 143

SUIM_assoc; Unstructured region C-term to UIM in Ataxin3
XM_036157162.1 → XP_036013055.1 ataxin-3 isoform X2

UniProtKB/TrEMBL

F6T5L3

Conserved Domains (2) summary

pfam02099
Location:9 → 163

Josephin

pfam16619
Location:264 → 322

SUIM_assoc; Unstructured region C-term to UIM in Ataxin3
XM_030246526.2 → XP_030102386.1 ataxin-3 isoform X5

UniProtKB/TrEMBL

F6T5L3, Q5M8S1

Related

ENSMUSP00000125082.2, ENSMUST00000160251.8

Conserved Domains (1) summary

pfam02099
Location:9 → 163

Josephin