9di2

Structural highlights

Disease

WDR48_HUMAN Autosomal recessive spastic paraplegia type 60.

Function

WDR48_HUMAN Regulator of deubiquitinating complexes. Acts as a strong activator of USP1 by enhancing the USP1-mediated deubiquitination of FANCD2; USP1 being almost inactive by itself. Also activates deubiquitinating activity of complexes containing USP12 and USP46, respectively. Activates deubiquitination by increasing the catalytic turnover without increasing the affinity of deubiquitinating enzymes for the substrate. In case of infection by Herpesvirus saimiri, may play a role in vesicular transport or membrane fusion events necessary for transport to lysosomes. Induces lysosomal vesicle formation via interaction with Herpesvirus saimiri tyrosine kinase-interacting protein (TIP). Subsequently, TIP recruits tyrosine-protein kinase LCK, resulting in down-regulation of T-cell antigen receptor TCR. May play a role in generation of enlarged endosomal vesicles via interaction with TIP. In case of infection by papillomavirus HPV11, promotes the maintenance of the viral genome via its interaction with HPV11 helicase E1.^{[1] [2] [3]}

References

1. ↑ Park J, Lee BS, Choi JK, Means RE, Choe J, Jung JU. Herpesviral protein targets a cellular WD repeat endosomal protein to downregulate T lymphocyte receptor expression. Immunity. 2002 Aug;17(2):221-33. PMID:12196293
2. ↑ Cohn MA, Kowal P, Yang K, Haas W, Huang TT, Gygi SP, D'Andrea AD. A UAF1-containing multisubunit protein complex regulates the Fanconi anemia pathway. Mol Cell. 2007 Dec 14;28(5):786-97. PMID:18082604 doi:http://dx.doi.org/10.1016/j.molcel.2007.09.031
3. ↑ Cohn MA, Kee Y, Haas W, Gygi SP, D'Andrea AD. UAF1 is a subunit of multiple deubiquitinating enzyme complexes. J Biol Chem. 2009 Feb 20;284(8):5343-51. doi: 10.1074/jbc.M808430200. Epub 2008, Dec 15. PMID:19075014 doi:http://dx.doi.org/10.1074/jbc.M808430200