Josephin domain (IPR006155)

Short name: Josephin

Overlapping homologous superfamilies


Domain relationships



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) in ataxin 3-like proteins. Josephin domain-containing proteins function as de-ubiquitination enzymes [PMID: 17696782]. Although it has originally been proposed that the Josephin domain could be an all-alpha helical domain distantly related to ENTH and VHS domains involved in membrane trafficking and regulatory adaptor function [PMID: 12486728], it is now believed that it is a mainly alpha helical cysteine-protease domain predicted to be active against ubiquitin chains or related substrates [PMID: 12944423, PMID: 14559776].

The Josephin domain contains two conserved histidines and one cysteine that is required for the ubiquitin protease activity [PMID: 12944423, PMID: 14559776] and two ubiquitin-binding sites [PMID: 19382171].

Some proteins known to contain a Josephin domain are:

  • 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 homologue).
  • Mammalian Josephin 1 and 2.
  • Drosophila melanogaster Josephin-like protein.
  • Arabidopsis thaliana Josephin-like protein.

GO terms

Biological Process

GO:0016579 protein deubiquitination

Molecular Function

GO:0004843 thiol-dependent ubiquitin-specific protease activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE profiles