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

Pathology

• CAG repeat expansion in SCA3/MJD1 gene encoding ataxin-3 in Machado-Joseph disease (spinocerebellar ataxia type 3, olivopontocerebellar ataxia 3)

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

More general terms

• ataxin
• nuclear protein
• phosphoprotein
• ubiquitin C-terminal hydrolase

Additional terms

• ataxin-3-like protein (Machado-Joseph disease protein 1-like, ATXN3L, MJDL)
• spinocerebellar ataxia type 3 (SCA-3); Machado-Joseph disease; Azorean disease

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4287
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4287
• OMIM: https://mirror.omim.org/entry/109150
• OMIM: https://mirror.omim.org/entry/607047
• UniProt: http://www.uniprot.org/uniprot/P54252.html