WDR48_HUMAN Loading...

WD repeat-containing protein 48

Regulator of deubiquitinating complexes, which acts as a strong activator of USP1, USP12 and USP46^1,2,3,4. Enhances the USP1-mediated deubiquitination of FANCD2; USP1 being almost inactive by itself^5,6. Activates deubiquitination by increasing the catalytic turnover without increasing the affinity of deubiquitinating enzymes for the substrate^7,8. Also activates deubiquitinating activity of complexes containing USP12^9,10,11. In complex with USP12, acts as a potential tumor suppressor by positively regulating PHLPP1 stability¹². Docks at the distal end of the USP12 fingers domain and induces a cascade of structural changes leading to the activation of the enzyme^13,14. Together with RAD51AP1, promotes DNA repair by stimulating RAD51-mediated homologous recombination^15,16,17. Binds single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA)^18,19,20. DNA-binding is required both for USP1-mediated deubiquitination of FANCD2 and stimulation of RAD51-mediated homologous recombination: both WDR48/UAF1 and RAD51AP1 have coordinated role in DNA-binding during these processes^21,22. Together with ATAD5 and by regulating USP1 activity, has a role in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA²³. Together with ATAD5, has a role in recruiting RAD51 to stalled forks during replication stress²⁴. (Microbial infection) 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 TIP²⁵. In case of infection by papillomavirus HPV11, promotes the maintenance of the viral genome via its interaction with HPV11 helicase E1²⁶.

AlphaFold DB , UniProt , Accession Q8TAF3, Species HUMAN (Homo sapiens, Human), Gene WDR48, Length 677 aa.