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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.

January 2004 / First entry.

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

JOSEPHIN, PS50957; Josephin domain profile  (MATRIX)

Sequences known to belong to this class detected by the profile: ALL Other sequence(s) detected in Swiss-Prot: NONE

• Domain architecture view of Swiss-Prot proteins matching PS50957 • Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS50957 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS50957 • Scan Swiss-Prot/TrEMBL entries against PS50957 • view ligand binding statistics

Matching PDB structures: 1YZB 2AGA 2DOS 2JRI ... [ALL]

1	Authors	Albrecht M., Hoffmann D., Evert B.O., Schmitt I., Wuellner U., Lengauer T.
	Title	Structural modeling of ataxin-3 reveals distant homology to adaptins.
	Source	Proteins 50:355-370(2003).
	PubMed ID	12486728
	DOI	10.1002/prot.10280

2	Authors	Scheel H., Tomiuk S., Hofmann K.
	Title	Elucidation of ataxin-3 and ataxin-7 function by integrative bioinformatics.
	Source	Hum. Mol. Genet. 12:2845-2852(2003).
	PubMed ID	12944423
	DOI	10.1093/hmg/ddg297

3	Authors	Burnett B., Li F., Pittman R.N.
	Title	The polyglutamine neurodegenerative protein ataxin-3 binds polyubiquitylated proteins and has ubiquitin protease activity.
	Source	Hum. Mol. Genet. 12:3195-3205(2003).
	PubMed ID	14559776
	DOI	10.1093/hmg/ddg344

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