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Aliases for ATXN3 Gene

Aliases for ATXN3 Gene

  • Ataxin 3 2 3 5
  • Spinocerebellar Ataxia Type 3 Protein 3 4
  • Machado-Joseph Disease Protein 1 3 4
  • SCA3 3 4
  • ATX3 3 4
  • MJD1 3 4
  • MJD 3 4
  • Machado-Joseph Disease (Spinocerebellar Ataxia 3, Olivopontocerebellar Ataxia 3, Autosomal Dominant, Ataxin 3) 2
  • Olivopontocerebellar Ataxia 3 3
  • EC 3.4.19.12 4
  • EC 3.4.22 61
  • Ataxin-3 3
  • Josephin 3
  • AT3 3
  • JOS 3

External Ids for ATXN3 Gene

Previous HGNC Symbols for ATXN3 Gene

  • SCA3
  • MJD

Previous GeneCards Identifiers for ATXN3 Gene

  • GC14M091599
  • GC14M092524
  • GC14M072705

Summaries for ATXN3 Gene

Entrez Gene Summary for ATXN3 Gene

  • Machado-Joseph disease, also known as spinocerebellar ataxia-3, is an autosomal dominant neurologic disorder. The protein encoded by this gene contains (CAG)n repeats in the coding region, and the expansion of these repeats from the normal 12-44 to 52-86 is one cause of Machado-Joseph disease. There is a negative correlation between the age of onset and CAG repeat numbers. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2016]

GeneCards Summary for ATXN3 Gene

ATXN3 (Ataxin 3) is a Protein Coding gene. Diseases associated with ATXN3 include Machado-Joseph Disease and Machado-Joseph Disease Type 1. Among its related pathways are Akt Signaling and Metabolism of proteins. GO annotations related to this gene include identical protein binding and thiol-dependent ubiquitin-specific protease activity. An important paralog of this gene is ATXN3L.

UniProtKB/Swiss-Prot for ATXN3 Gene

  • Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates. Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins. Involved in degradation of misfolded chaperone substrates via its interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, and restricts the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. In response to misfolded substrate ubiquitination, mediates deubiquitination of monoubiquitinated STUB1/CHIP. Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription.

Gene Wiki entry for ATXN3 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ATXN3 Gene

Genomics for ATXN3 Gene

Regulatory Elements for ATXN3 Gene

Enhancers for ATXN3 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH14F092105 0.9 FANTOM5 ENCODE 16.2 +0.4 431 2.2 HDGF ATF1 PKNOX1 ARID4B SIN3A DMAP1 GLIS2 ZNF143 KLF7 FOS ATXN3 NDUFB1 RIN3 SLC24A4 CATSPERB ENSG00000279963
GH14F092107 1.3 Ensembl ENCODE 14.9 -1.9 -1922 1.4 GTF2F1 DRAP1 TBP ESRRA PKNOX1 SAP130 DDX20 ZMYM3 CDC5L ZNF644 ATXN3 NDUFB1
GH14F092120 0.5 ENCODE 11.4 -15.5 -15498 2.9 HDGF PKNOX1 ARNT WRNIP1 ARID4B SIN3A DMAP1 ZNF2 YY1 ZNF143 CPSF2 NDUFB1 TRIP11 GOLGA5 ATXN3 GC14P092168
GH14F092160 0.6 ENCODE 11.1 -54.3 -54251 1.2 CBX5 CEBPB FOS TRIM28 NDUFB1 CPSF2 ATXN3 GC14P092168
GH14F091979 1.3 FANTOM5 Ensembl ENCODE 9 +126.4 126420 1.4 JUN GATA3 FOSL2 FOS MAFK CREM ZNF362 BHLHE40 JUNB USF2 FBLN5 TRIP11 TC2N ATXN3 SLC24A4 PPP4R3A PTMAP7
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around ATXN3 on UCSC Golden Path with GeneCards custom track

Promoters for ATXN3 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000099457 321 1801 HDGF ARID4B SIN3A DMAP1 GLIS2 ZNF143 KLF7 FOS KLF13 SP3

Transcription factor binding sites by QIAGEN in the ATXN3 gene promoter:

Genomic Location for ATXN3 Gene

Chromosome:
14
Start:
92,038,652 bp from pter
End:
92,106,621 bp from pter
Size:
67,970 bases
Orientation:
Minus strand

Genomic View for ATXN3 Gene

Genes around ATXN3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ATXN3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ATXN3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ATXN3 Gene

Proteins for ATXN3 Gene

  • Protein details for ATXN3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P54252-ATX3_HUMAN
    Recommended name:
    Ataxin-3
    Protein Accession:
    P54252
    Secondary Accessions:
    • A7LFZ5
    • D6RDL9
    • E9PB63
    • O15284
    • O15285
    • O15286
    • Q8N189
    • Q96TC3
    • Q96TC4
    • Q9H3N0

    Protein attributes for ATXN3 Gene

    Size:
    364 amino acids
    Molecular mass:
    41781 Da
    Quaternary structure:
    • Interacts with STUB1/CHIP (when monoubiquitinated) (By similarity). Interacts with DNA repair proteins RAD23A and RAD23B.

    Three dimensional structures from OCA and Proteopedia for ATXN3 Gene

    Alternative splice isoforms for ATXN3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ATXN3 Gene

Selected DME Specific Peptides for ATXN3 Gene

P54252:
  • RPKLIGEE
  • EGYSIFVV
  • LCAQHCLNNLLQGEYFSPVEL
  • IFHEKQEG
  • FVVKGDLPDCEADQLLQ
  • GPELISDT
  • NMDDSGFFSIQVISNALKVWGLELILFNSPEYQRL
  • WFNLNSLL

Post-translational modifications for ATXN3 Gene

  • Monoubiquitinated N-terminally by UBE2W, possibly leading to activate the deubiquitinating enzyme activity.
  • Ubiquitination at Lys 117, Lys 190, Lys 200, and Lys 291
  • Modification sites at PhosphoSitePlus

Domains & Families for ATXN3 Gene

Gene Families for ATXN3 Gene

Protein Domains for ATXN3 Gene

Graphical View of Domain Structure for InterPro Entry

P54252

UniProtKB/Swiss-Prot:

ATX3_HUMAN :
  • The UIM domains bind ubiquitin and interact with various E3 ubiquitin-protein ligase, such as STUB1/CHIP. They are essential to limit the length of ubiquitin chains (By similarity).
Domain:
  • The UIM domains bind ubiquitin and interact with various E3 ubiquitin-protein ligase, such as STUB1/CHIP. They are essential to limit the length of ubiquitin chains (By similarity).
  • Contains 1 Josephin domain.
  • Contains 3 UIM (ubiquitin-interacting motif) domains.
genes like me logo Genes that share domains with ATXN3: view

Function for ATXN3 Gene

Molecular function for ATXN3 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
UniProtKB/Swiss-Prot Function:
Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates. Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins. Involved in degradation of misfolded chaperone substrates via its interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, and restricts the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. In response to misfolded substrate ubiquitination, mediates deubiquitination of monoubiquitinated STUB1/CHIP. Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription.

Enzyme Numbers (IUBMB) for ATXN3 Gene

Gene Ontology (GO) - Molecular Function for ATXN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001012 RNA polymerase II regulatory region DNA binding IEA --
GO:0004407 histone deacetylase activity IEA --
GO:0004843 thiol-dependent ubiquitin-specific protease activity IEA,ISS --
GO:0005515 protein binding IPI 16525503
GO:0008233 peptidase activity IEA --
genes like me logo Genes that share ontologies with ATXN3: view
genes like me logo Genes that share phenotypes with ATXN3: view

Human Phenotype Ontology for ATXN3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for ATXN3 Gene

MGI Knock Outs for ATXN3:

Animal Model Products

miRNA for ATXN3 Gene

miRTarBase miRNAs that target ATXN3

Clone Products

  • Addgene plasmids for ATXN3

Flow Cytometry Products

No data available for Transcription Factor Targets and HOMER Transcription for ATXN3 Gene

Localization for ATXN3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ATXN3 Gene

Nucleus matrix. Note=Predominantly nuclear, but not exclusively, inner nuclear matrix.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for ATXN3 Gene COMPARTMENTS Subcellular localization image for ATXN3 gene
Compartment Confidence
cytosol 5
nucleus 5
mitochondrion 4
cytoskeleton 1
endoplasmic reticulum 1
extracellular 1

Gene Ontology (GO) - Cellular Components for ATXN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 24548080
GO:0005654 nucleoplasm TAS 9580663
GO:0005737 cytoplasm TAS 9124802
GO:0005759 mitochondrial matrix ISS --
GO:0005789 colocalizes_with endoplasmic reticulum membrane IDA 17000876
genes like me logo Genes that share ontologies with ATXN3: view

Pathways & Interactions for ATXN3 Gene

genes like me logo Genes that share pathways with ATXN3: view

Gene Ontology (GO) - Biological Process for ATXN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000226 microtubule cytoskeleton organization IMP 20637808
GO:0006289 nucleotide-excision repair TAS 10915768
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006508 proteolysis IEA --
genes like me logo Genes that share ontologies with ATXN3: view

No data available for SIGNOR curated interactions for ATXN3 Gene

Drugs & Compounds for ATXN3 Gene

(3) Drugs for ATXN3 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for ATXN3 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with ATXN3: view

Transcripts for ATXN3 Gene

Unigene Clusters for ATXN3 Gene

Ataxin 3:
Representative Sequences:

Clone Products

  • Addgene plasmids for ATXN3

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for ATXN3 Gene

ExUns: 1 ^ 2a · 2b ^ 3a · 3b ^ 4a · 4b ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b · 10c ^ 11a · 11b
SP1: - - - -
SP2: - - - - -
SP3: - - - - - -
SP4: - - - - -
SP5: - - - - - - -
SP6: - - -
SP7: - - - - - - -
SP8: -
SP9: - - -
SP10:

Relevant External Links for ATXN3 Gene

GeneLoc Exon Structure for
ATXN3
ECgene alternative splicing isoforms for
ATXN3

Expression for ATXN3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ATXN3 Gene

Protein differential expression in normal tissues from HIPED for ATXN3 Gene

This gene is overexpressed in Heart (17.0), Testis (10.9), and Peripheral blood mononuclear cells (7.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for ATXN3 Gene



Protein tissue co-expression partners for ATXN3 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of ATXN3 Gene:

ATXN3

SOURCE GeneReport for Unigene cluster for ATXN3 Gene:

Hs.532632

mRNA Expression by UniProt/SwissProt for ATXN3 Gene:

P54252-ATX3_HUMAN
Tissue specificity: Ubiquitous.
genes like me logo Genes that share expression patterns with ATXN3: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for ATXN3 Gene

Orthologs for ATXN3 Gene

This gene was present in the common ancestor of animals.

Orthologs for ATXN3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ATXN3 34 35
  • 99.33 (n)
dog
(Canis familiaris)
Mammalia -- 35
  • 94 (a)
ManyToMany
ATXN3 34
  • 91.93 (n)
-- 35
  • 89 (a)
ManyToMany
-- 35
  • 85 (a)
ManyToMany
cow
(Bos Taurus)
Mammalia ATXN3 34 35
  • 92.51 (n)
mouse
(Mus musculus)
Mammalia Atxn3 34 16 35
  • 87.61 (n)
rat
(Rattus norvegicus)
Mammalia Atxn3 34
  • 85.45 (n)
oppossum
(Monodelphis domestica)
Mammalia -- 35
  • 85 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia -- 35
  • 80 (a)
OneToMany
chicken
(Gallus gallus)
Aves ATXN3 34 35
  • 78.77 (n)
lizard
(Anolis carolinensis)
Reptilia -- 35
  • 74 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia atxn3 34
  • 72.1 (n)
Str.4713 34
African clawed frog
(Xenopus laevis)
Amphibia Xl.3069 34
zebrafish
(Danio rerio)
Actinopterygii atxn3 34
  • 64 (n)
ATXN3 35
  • 60 (a)
OneToMany
zgc56323 34
worm
(Caenorhabditis elegans)
Secernentea atx-3 34 35
  • 51.07 (n)
Species where no ortholog for ATXN3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for ATXN3 Gene

ENSEMBL:
Gene Tree for ATXN3 (if available)
TreeFam:
Gene Tree for ATXN3 (if available)

Paralogs for ATXN3 Gene

Paralogs for ATXN3 Gene

(1) SIMAP similar genes for ATXN3 Gene using alignment to 201 proteins:

Pseudogenes.org Pseudogenes for ATXN3 Gene

genes like me logo Genes that share paralogs with ATXN3: view

Variants for ATXN3 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for ATXN3 Gene

ATX3_HUMAN-P54252
The MJD1a allele carries a single nucleotide substitution in codon 349 generating a stop codon instead of a Tyr. In the Japanese population, the MJD1a allele seems to be significantly associated with Gln expansion.
ATX3_HUMAN-P54252
The poly-Gln region of ATXN3 is highly polymorphic (14 to 41 repeats) in the normal population and is expanded to about 55-82 repeats in spinocerebellar ataxia 3 (SCA3) patients.

Sequence variations from dbSNP and Humsavar for ATXN3 Gene

SNP ID Clin Chr 14 pos Sequence Context AA Info Type
rs1048755 Likely benign 92,082,441(-) AACGA(A/G)TGTTA intron-variant, nc-transcript-variant, reference, missense
rs12895357 Likely benign 92,071,010(+) GTCCC(C/G)CTGCT nc-transcript-variant, reference, missense
rs12896583 Likely benign 92,071,035(+) TGCTG(C/T)TGCTG nc-transcript-variant, reference, synonymous-codon, missense
rs12896588 Likely benign 92,071,043(+) ctgct(G/T)ttgct nc-transcript-variant, reference, missense
rs12896589 Likely benign 92,071,044(+) tgctt(C/T)tgctg nc-transcript-variant, reference, synonymous-codon, missense

Structural Variations from Database of Genomic Variants (DGV) for ATXN3 Gene

Variant ID Type Subtype PubMed ID
dgv1956n100 CNV gain 25217958
nsv1045760 CNV gain 25217958
nsv1116040 CNV deletion 24896259
nsv1122926 CNV deletion 24896259
nsv1122927 CNV deletion 24896259
nsv456395 CNV loss 19166990
nsv527458 CNV loss 19592680
nsv565519 CNV loss 21841781
nsv85878 CNV insertion 16902084

Variation tolerance for ATXN3 Gene

Residual Variation Intolerance Score: 41.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 12.92; 94.89% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for ATXN3 Gene

Human Gene Mutation Database (HGMD)
ATXN3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ATXN3

Disorders for ATXN3 Gene

MalaCards: The human disease database

(28) MalaCards diseases for ATXN3 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
machado-joseph disease
  • azorean disease
machado-joseph disease type 1
  • sca3, joseph type
machado-joseph disease type 3
  • sca3, machado type
machado-joseph disease type 2
  • sca3, thomas type
parkinson disease, late-onset
  • parkinson disease
- elite association - COSMIC cancer census association via MalaCards
Search ATXN3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

ATX3_HUMAN
  • Spinocerebellar ataxia 3 (SCA3) [MIM:109150]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to cerebellum degeneration with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. The molecular defect in SCA3 is the a CAG repeat expansion in ATX3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease. {ECO:0000269 PubMed:7874163}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for ATXN3

Genetic Association Database (GAD)
ATXN3
Human Genome Epidemiology (HuGE) Navigator
ATXN3
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
ATXN3
genes like me logo Genes that share disorders with ATXN3: view

No data available for Genatlas for ATXN3 Gene

Publications for ATXN3 Gene

  1. [Detection of the CAG trinucleotide repeats of MJD1 gene by recombinant DNA technology]. (PMID: 20017304) Zhang S. … Tang B.S. (Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2009) 3 22 46 64
  2. Josephin domain-containing proteins from a variety of species are active de-ubiquitination enzymes. (PMID: 17696782) Tzvetkov N. … Breuer P. (Biol. Chem. 2007) 3 4 22 64
  3. Lack of mutations in spinocerebellar ataxia type 2 and 3 genes in a Taiwanese (ethnic Chinese) cohort of familial and early-onset parkinsonism. (PMID: 17440947) Lin C.H. … Wu R.M. (Am. J. Med. Genet. B Neuropsychiatr. Genet. 2007) 3 22 46 64
  4. Deubiquitinating function of ataxin-3: insights from the solution structure of the Josephin domain. (PMID: 16118278) Mao Y. … De Camilli P. (Proc. Natl. Acad. Sci. U.S.A. 2005) 3 4 22 64
  5. Structural modeling of ataxin-3 reveals distant homology to adaptins. (PMID: 12486728) Albrecht M. … Lengauer T. (Proteins 2003) 3 4 22 64

Products for ATXN3 Gene

Sources for ATXN3 Gene

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