Tbio ATXN3 Ataxin-3

Protein Classes

PANTHER Classes

Protein / Transcription Factor / Ataxin-3

Protein / ... / Cysteine Protease / Ataxin-3

DTO Classes

Protein / Enzyme / Protease / Cysteine Protease / Ataxin-3

Protein Summary

Description

Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates (PubMed:12297501, PubMed:17696782, PubMed:23625928, PubMed:28445460, PubMed:16118278). Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins (PubMed:17696782). 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 (By similarity). Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription (PubMed:12297501). Regulates autophagy via the deubiquitination of 'Lys-402' of BECN1 leading to the stabilization of BECN1 (PubMed:28445460). 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]

Uniprot Accession IDs

• P54252
• A7LFZ5
• D6RDL9
• E9PB63
• O15284
• O15285
• O15286
• Q8N189
• Q96TC3
• Q96TC4
• Q9H3N0

Gene Name

• ATXN3

Ensembl ID

• ENST00000340660
• ENSP00000339110
• ENSG00000066427
• ENST00000502250
• ENSP00000425322
• ENST00000503767
• ENSP00000426697
• ENST00000532032
• ENSP00000437157
• ENST00000558190
• ENSP00000478320
• ENST00000644486
• ENSP00000496695

Symbol

• ATX3
• MJD
• MJD1
• SCA3
• AT3
• JOS
• MJD
• ATX3
• MJD1
• SCA3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
co-expressed gene	1
microRNA	0.84
biological process	0.8
virus perturbation	0.79
transcription factor binding site profile	0.78

Related Tools

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 535.05   (req: < 5)

Gene RIFs: 153   (req: <= 3)

Antibodies: 302   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 535.05   (req: >= 5)

Gene RIFs: 153   (req: > 3)

Antibodies: 302   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 29

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

GWAS Traits (2)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 2 of 2

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
forced expiratory volume	EFO_0004314	1	1	1		41.8
vital capacity	EFO_0004312	1	1	1		21.2

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 2 of 2

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
forced expiratory volume	EFO_0004314	1		41.8
vital capacity	EFO_0004312	1		21.2

Reset Zoom  Beta Count   Odds Ratio

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	ataxin 3	VGNC:12976	738729
Macaque	ataxin 3		720515
Mouse	ataxin 3	MGI:1099442	110616
Rat	ataxin 3	RGD:621567	60331
Dog	ataxin 3		480229

Species	Name	OMA	EggNOG	Inparanoid
Chimp	ataxin 3
Macaque	ataxin 3
Mouse	ataxin 3
Rat	ataxin 3
Dog	ataxin 3

Protein Structure (7 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P54252-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 7

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (10)

Reactome (9)

KEGG (1)

Deubiquitination (R-HSA-5688426)

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Find Similar Targets

Items per page:

5

1 – 5 of 9

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Deubiquitination	278 targets	R-HSA-5688426
Reactome	FOXO-mediated transcription	68 targets	R-HSA-9614085
Reactome	FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	30 targets	R-HSA-9615017
Reactome	Gene expression (Transcription)	1452 targets	R-HSA-74160
Reactome	Generic Transcription Pathway	1195 targets	R-HSA-212436

Name	Explore in Pharos	Explore in Source
Deubiquitination	278 targets	R-HSA-5688426
FOXO-mediated transcription	68 targets	R-HSA-9614085
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	30 targets	R-HSA-9615017
Gene expression (Transcription)	1452 targets	R-HSA-74160
Generic Transcription Pathway	1195 targets	R-HSA-212436

Gene Ontology Terms (39)

Functions (9)

Components (10)

Processes (20)

Find Similar Targets

Items per page:

10

1 – 9 of 9

GO Term	Evidence	Assigned by
Lys48-specific deubiquitinase activity	Inferred from Direct Assay (IDA)	ParkinsonsUK-UCL
Lys63-specific deubiquitinase activity	Inferred from Direct Assay (IDA)	ParkinsonsUK-UCL
ATPase binding	Inferred from Physical Interaction (IPI)	ParkinsonsUK-UCL
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
ubiquitin protein ligase binding	Inferred from Physical Interaction (IPI)	ParkinsonsUK-UCL
thiol-dependent ubiquitin-specific protease activity	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
thiol-dependent ubiquitinyl hydrolase activity	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
histone deacetylase activity	Inferred from Electronic Annotation (IEA)	Ensembl
RNA polymerase II regulatory region DNA binding	Inferred from Electronic Annotation (IEA)	Ensembl

Protein-Protein Interactions (157)

Explore Interacting Targets

1 – 10 of 157

• See Interactions on String-DB

TOMM20L

Tdark

Novelty: 4.50556416

p_int: 0.999999999

p_ni: 1e-9

Score: 0.485

Data Source: BioPlex,STRINGDB

IGF2

Tbio

Novelty: 0.00021277

p_int: 0.999996585

p_ni: 0.000002867

p_wrong: 5.48e-7

Data Source: BioPlex

TMEM31

Tdark

Novelty: 0.65381391

p_int: 0.999992214

p_ni: 0.000005918

p_wrong: 0.000001868

Data Source: BioPlex

DND1

Tbio

Novelty: 0.0287312

p_int: 0.999412306

p_ni: 0.000028795

p_wrong: 0.000558899

Score: 0.269

Data Source: BioPlex,STRINGDB

AEBP2

Tbio

Novelty: 0.05974483

p_int: 0.999131187

p_ni: 0.000045903

p_wrong: 0.00082291

Score: 0.308

Data Source: BioPlex,STRINGDB

UBB

Tbio

Novelty: 0.00661254

Score: 0.997

Data Source: STRINGDB

UBC

Tbio

Novelty: 0.00204643

Score: 0.997

Data Source: STRINGDB

UBA52

Tbio

Novelty: 0.01637744

Score: 0.995

Data Source: STRINGDB

VCP

Tchem

Family: Enzyme

Novelty: 0.00103317

Score: 0.994

Data Source: Reactome,STRINGDB

RAD23A

Tbio

Novelty: 0.01603801

Score: 0.989

Data Source: Reactome,STRINGDB

Publication Statistics

PubMed Score  535.05

PubMed score by year

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PubTator Score  854.7

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

Show Full Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Alternative splicing
Complete proteome
Hydrolase
Isopeptide bond
Neurodegeneration
Nucleus
Phosphoprotein
Polymorphism
Protease

GWAS Trait Find Similar Targets

forced expiratory volume
vital capacity

MGI Phenotype Find Similar Targets

behavior/neurological phenotype
homeostasis/metabolism phenotype
nervous system phenotype