{PDOC50957}
{PS50957; JOSEPHIN}
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* Josephin domain profile *
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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-alpha
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 alpha 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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: January 2004 / First entry.

[ 1] Albrecht M., Hoffmann D., Evert B.O., Schmitt I., Wuellner U.,
     Lengauer T.
     "Structural modeling of ataxin-3 reveals distant homology to
     adaptins."
     Proteins 50:355-370(2003).
     PubMed=12486728; DOI=10.1002/prot.10280
[ 2] Scheel H., Tomiuk S., Hofmann K.
     "Elucidation of ataxin-3 and ataxin-7 function by integrative
     bioinformatics."
     Hum. Mol. Genet. 12:2845-2852(2003).
     PubMed=12944423; DOI=10.1093/hmg/ddg297
[ 3] Burnett B., Li F., Pittman R.N.
     "The polyglutamine neurodegenerative protein ataxin-3 binds
     polyubiquitylated proteins and has ubiquitin protease activity."
     Hum. Mol. Genet. 12:3195-3205(2003).
     PubMed=14559776; DOI=10.1093/hmg/ddg344

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