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ataxin-3; Machado-Joseph disease protein 1; spinocerebellar ataxia type 3 protein (ATXN3, ATX3, MJD, MJD1, SCA3)
Function:
- interacts with key regulators (CBP, p300 & PCAF) of transcription & represses transcription
- acts as a histone- binding protein that regulates transcription
- interacts with DNA repair proteins RAD23A & RAD23B
- acts as a deubiquitinating enzyme
ubiquitin C-terminal thioester + H2O ubiquitin + a thiol
Structure:
- contains 1 Josephin domain
- contains 3 UIM (ubiquitin-interacting motif) repeats
Compartment:
- nuclear matrix, inner nuclear matrix
- predominantly nuclear, but not exclusively
Alternative splicing: named isoforms=3
Expression:
- ubiquitous
Polymorphism:
- the poly-Gln region of ATXN3 is highly polymorphic (14 to 41 repeats) in the normal population & is expanded to ~ 55-82 repeats in spinocerebellar ataxia 3 (SCA3) patients
- 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
Pathology:
- CAG repeat expansion in SCA3/MJD1 gene encoding ataxin-3 in Machado-Joseph disease (spinocerebellar ataxia type 3, olivopontocerebellar ataxia 3)
Related
ataxin-3-like protein (Machado-Joseph disease protein 1-like, ATXN3L, MJDL)
SCA3/MJD1 gene
spinocerebellar ataxia type 3 (SCA-3); Machado-Joseph disease; Azorean disease
General
ataxin
nuclear protein
phosphoprotein
ubiquitin C-terminal hydrolase; UCH; ubiquitin thiolesterase; ubiquitin-specific processing protease; deubiquitinating enzyme
Properties
SIZE: entity length = 364 aa
MW = 42 kD
COMPARTMENT: cell nucleus
MOTIF: Josephin {1-180}
MOTIF: cysteine residue {C14}
histidine residue {H119}
asparagine residue {N134}
Ser phosphorylation site {S219}
UIM {224-243}
UIM {244-263}
glutamine-rich region {292-305}
MOTIF: glutamine residue (SEVERAL)
UIM {331-348}
Database Correlations
OMIM correlations
UniProt P54252
PFAM correlations
Entrez Gene 4287
Kegg hsa:4287
ENZYME 3.1.2.15
References
- UniProt :accession P54252
- NIEHS-SNPs
http://egp.gs.washington.edu/data/atxn3/
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/ATXN3