P54252 · ATX3_HUMAN
- ProteinAtaxin-3
- GeneATXN3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids361 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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).
Acts as a negative regulator of mTORC1 signaling in response to amino acid deprivation by mediating deubiquitination of RHEB, thereby promoting RHEB inactivation by the TSC-TBC complex (PubMed:33157014).
Regulates autophagy via the deubiquitination of 'Lys-402' of BECN1 leading to the stabilization of BECN1 (PubMed:28445460).
Catalytic activity
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 14 | Nucleophile | ||||
Sequence: C | ||||||
Active site | 119 | Proton acceptor | ||||
Sequence: H | ||||||
Active site | 134 | |||||
Sequence: N |
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameAtaxin-3
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP54252
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Spinocerebellar ataxia 3 (SCA3)
- Note
- DescriptionSpinocerebellar 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.
- See alsoMIM:109150
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 14 | Loss of deubiquitination activity. | ||||
Sequence: C → A | ||||||
Natural variant | VAR_013688 | 212 | in dbSNP:rs1048755 | |||
Sequence: V → M | ||||||
Mutagenesis | 236 | Inhibits substrate trapping. | ||||
Sequence: S → A | ||||||
Mutagenesis | 256 | Inhibits substrate trapping. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_013689 | 306 | ||||
Sequence: G → QQQQQQQQQQQQR | ||||||
Mutagenesis | 335 | No effect on ubiquitination. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_082841 | 349-364 | In isoform P54252-1; in short isoform 1, due to a stop-gain single nucleotide variant, has reduced half-life due to increased proteasomal degradation, has reduced solubility and increased tendency to form aggregates, increased localization to the nucleus | |||
Sequence: Missing |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 408 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for cross-link, chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Cross-link | 1 | UniProt | Peptide (Met-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: M | |||||||
Chain | PRO_0000053831 | 1-361 | UniProt | Ataxin-3 | |||
Sequence: MESIFHEKQEGSLCAQHCLNNLLQGEYFSPVELSSIAHQLDEEERMRMAEGGVTSEDYRTFLQQPSGNMDDSGFFSIQVISNALKVWGLELILFNSPEYQRLRIDPINERSFICNYKEHWFTVRKLGKQWFNLNSLLTGPELISDTYLALFLAQLQQEGYSIFVVKGDLPDCEADQLLQMIRVQQMHRPKLIGEELAQLKEQRVHKTDLERVLEANDGSGMLDEDEEDLQRALALSRQEIDMEDEEADLRRAIQLSMQGSSRNISQDMTQTSGTNLTSEELRKRREAYFEKQQQKQQQQQQQQQQGDLSGQSSHPCERPATSSGALGSDLGDAMSEEDMLQAAVTMSLETVRNDLKTEGKK | |||||||
Cross-link | 200 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Modified residue | 219 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 265 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 265 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 272 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 328 | UniProt | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with DNA repair proteins RAD23A and RAD23B (PubMed:16020535, PubMed:30455355).
Interacts with BECN1 (via its poly-Gln domain) (PubMed:28445460).
Interacts with PRKN, UBR2, VCP and tubulin. Short isoform 1 interacts with CASP7 (PubMed:30455355).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 1-180 | Josephin | ||||
Sequence: MESIFHEKQEGSLCAQHCLNNLLQGEYFSPVELSSIAHQLDEEERMRMAEGGVTSEDYRTFLQQPSGNMDDSGFFSIQVISNALKVWGLELILFNSPEYQRLRIDPINERSFICNYKEHWFTVRKLGKQWFNLNSLLTGPELISDTYLALFLAQLQQEGYSIFVVKGDLPDCEADQLLQM | ||||||
Domain | 224-243 | UIM 1 | ||||
Sequence: EDEEDLQRALALSRQEIDME | ||||||
Domain | 244-263 | UIM 2 | ||||
Sequence: DEEADLRRAIQLSMQGSSRN | ||||||
Compositional bias | 258-277 | Polar residues | ||||
Sequence: QGSSRNISQDMTQTSGTNLT | ||||||
Region | 258-338 | Disordered | ||||
Sequence: QGSSRNISQDMTQTSGTNLTSEELRKRREAYFEKQQQKQQQQQQQQQQGDLSGQSSHPCERPATSSGALGSDLGDAMSEED | ||||||
Compositional bias | 292-319 | Polar residues | ||||
Sequence: QQQKQQQQQQQQQQGDLSGQSSHPCERP | ||||||
Domain | 331-349 | UIM 3 | ||||
Sequence: GDAMSEEDMLQAAVTMSLE |
Domain
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 5 isoforms produced by Alternative splicing.
P54252-2
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name2
- Length361
- Mass (Da)41,250
- Last updated2017-12-20 v5
- Checksum90C3EF73BB26CAFD
P54252-1
- Name1
- SynonymsMJD1a
- Differences from canonical
- 332-361: DAMSEEDMLQAAVTMSLETVRNDLKTEGKK → KACSPFIMFATFTLYLTYELHVIFALHYSSFPL
P54252-3
- Name3
- Differences from canonical
- 10-64: Missing
P54252-4
- Name4
- Differences from canonical
- 63-77: Missing
P54252-5
- Name5
- Differences from canonical
- 1-179: Missing
Computationally mapped potential isoform sequences
There are 24 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A2R8Y888 | A0A2R8Y888_HUMAN | ATXN3 | 87 | ||
A0A2R8Y3X7 | A0A2R8Y3X7_HUMAN | ATXN3 | 351 | ||
C9JQV6 | C9JQV6_HUMAN | ATXN3 | 291 | ||
D6R9I5 | D6R9I5_HUMAN | ATXN3 | 99 | ||
G3V4U9 | G3V4U9_HUMAN | ATXN3 | 278 | ||
G3V5H3 | G3V5H3_HUMAN | ATXN3 | 161 | ||
G3V3R7 | G3V3R7_HUMAN | ATXN3 | 329 | ||
G3V3S5 | G3V3S5_HUMAN | ATXN3 | 114 | ||
G3V3T0 | G3V3T0_HUMAN | ATXN3 | 95 | ||
G3V3T6 | G3V3T6_HUMAN | ATXN3 | 126 | ||
G3V4B1 | G3V4B1_HUMAN | ATXN3 | 110 | ||
G3V4F4 | G3V4F4_HUMAN | ATXN3 | 159 | ||
G3V4F5 | G3V4F5_HUMAN | ATXN3 | 150 | ||
G3V526 | G3V526_HUMAN | ATXN3 | 200 | ||
G3V328 | G3V328_HUMAN | ATXN3 | 260 | ||
G3V390 | G3V390_HUMAN | ATXN3 | 110 | ||
G3V3A6 | G3V3A6_HUMAN | ATXN3 | 78 | ||
G3V2G1 | G3V2G1_HUMAN | ATXN3 | 223 | ||
G3V2G2 | G3V2G2_HUMAN | ATXN3 | 150 | ||
D3VVP3 | D3VVP3_HUMAN | ATXN3 | 79 | ||
A0A0A0MS38 | A0A0A0MS38_HUMAN | ATXN3 | 310 | ||
E9PJN5 | E9PJN5_HUMAN | ATXN3 | 205 | ||
S4R399 | S4R399_HUMAN | ATXN3 | 202 | ||
F5H211 | F5H211_HUMAN | ATXN3 | 370 |
Features
Showing features for alternative sequence, sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_047085 | 1-179 | in isoform 5 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_002783 | 10-64 | in isoform 3 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_047086 | 63-77 | in isoform 4 | |||
Sequence: Missing | ||||||
Sequence conflict | 252 | in Ref. 2; AAB63352/AAB63353/AAB63354 | ||||
Sequence: A → T | ||||||
Compositional bias | 258-277 | Polar residues | ||||
Sequence: QGSSRNISQDMTQTSGTNLT | ||||||
Compositional bias | 292-319 | Polar residues | ||||
Sequence: QQQKQQQQQQQQQQGDLSGQSSHPCERP | ||||||
Alternative sequence | VSP_002784 | 332-361 | in isoform 1 | |||
Sequence: DAMSEEDMLQAAVTMSLETVRNDLKTEGKK → KACSPFIMFATFTLYLTYELHVIFALHYSSFPL |
Polymorphism
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
S75313 EMBL· GenBank· DDBJ | AAB33571.1 EMBL· GenBank· DDBJ | mRNA | ||
U64820 EMBL· GenBank· DDBJ | AAB63352.1 EMBL· GenBank· DDBJ | mRNA | ||
U64821 EMBL· GenBank· DDBJ | AAB63353.1 EMBL· GenBank· DDBJ | mRNA | ||
U64822 EMBL· GenBank· DDBJ | AAB63354.1 EMBL· GenBank· DDBJ | mRNA | ||
AB050194 EMBL· GenBank· DDBJ | BAB18798.1 EMBL· GenBank· DDBJ | mRNA | ||
AB038653 EMBL· GenBank· DDBJ | BAB55645.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AB038653 EMBL· GenBank· DDBJ | BAB55646.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
EU009923 EMBL· GenBank· DDBJ | ABS29269.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AL049872 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL121773 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471061 EMBL· GenBank· DDBJ | EAW81472.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC033711 EMBL· GenBank· DDBJ | AAH33711.1 EMBL· GenBank· DDBJ | mRNA |