PROSITE documentation PDOC50957
Josephin domain profile


The Josephin domain is an eukaryotic protein module of about 180 residues, which occurs in stand-alone form in Josephin-like proteins, and as an amino-terminal domain associated with two or three copies of the ubiquitin-interacting motif (UIM) (see <PDOC50330>) in ataxin 3-like proteins. Although it has originally been proposed that the Josephin domain could be an all-α helical domain distantly related to ENTH (see <PDOC50942>) and VHS (see <PDOC50179>) domains involved in membrane trafficking and regulatory adaptor function [1], it is now believed that it is a mainly α helical cysteine-protease domain predicted to be active against ubiquitin chains or related substrates [2,3].

The Josephin domain contains two conserved histidines and one cysteine that is required for the ubiquitin protease activity [2,3].

Some proteins known to contain a Josephin domain are listed below:

  • Animal Machado-Joseph disease protein 1 (Ataxin 3). It interacts with key regulators (CBP, p300 and PCAF) of transcription and represses transcription.
  • Plant Machado-Joseph disease-like protein (MJD1a-like) (Ataxin 3 homolog).
  • Mammalian Josephin 1 and 2.
  • Drosophila melanogaster Josephin-like protein.
  • Arabidopsis thaliana Josephin-like protein.

The profile we developed spans the entire Josephin domain.

Last update:

January 2004 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

JOSEPHIN, PS50957; Josephin domain profile  (MATRIX)


1AuthorsAlbrecht M. Hoffmann D. Evert B.O. Schmitt I. Wuellner U. Lengauer T.
TitleStructural modeling of ataxin-3 reveals distant homology to adaptins.
SourceProteins 50:355-370(2003).
PubMed ID12486728

2AuthorsScheel H. Tomiuk S. Hofmann K.
TitleElucidation of ataxin-3 and ataxin-7 function by integrative bioinformatics.
SourceHum. Mol. Genet. 12:2845-2852(2003).
PubMed ID12944423

3AuthorsBurnett B. Li F. Pittman R.N.
TitleThe polyglutamine neurodegenerative protein ataxin-3 binds polyubiquitylated proteins and has ubiquitin protease activity.
SourceHum. Mol. Genet. 12:3195-3205(2003).
PubMed ID14559776

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