WDR48

The protein encoded by this gene has been shown to interact with ubiquitin specific peptidase 1 (USP1), activating the deubiquitinating activity of USP1 and allowing it to remove the ubiquitin moiety from monoubiquitinated FANCD2. FANCD2 is ubiquitinated in response to DNA damage.

WD Repeat Domain 48

Regulator of deubiquitinating complexes, which acts as a strong activator of USP1, USP12 and USP46 (PubMed:18082604, PubMed:19075014, PubMed:31253762, PubMed:26388029).
Enhances the USP1-mediated deubiquitination of FANCD2; USP1 being almost inactive by itself (PubMed:18082604, PubMed:31253762).
Activates deubiquitination by increasing the catalytic turnover without increasing the affinity of deubiquitinating enzymes for the substrate (PubMed:19075014, PubMed:27373336).
Also activates deubiquitinating activity of complexes containing USP12 (PubMed:19075014, PubMed:27650958, PubMed:27373336).
In complex with USP12, acts as a potential tumor suppressor by positively regulating PHLPP1 stability (PubMed:24145035).
Docks at the distal end of the USP12 fingers domain and induces a cascade of structural changes leading to the activation of the enzyme (PubMed:27650958, PubMed:27373336).
Together with RAD51AP1, promotes DNA repair by stimulating RAD51-mediated homologous recombination (PubMed:27463890, PubMed:27239033, PubMed:32350107).
Binds single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) (PubMed:27239033, PubMed:31253762, PubMed:32350107).
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 (PubMed:31253762, PubMed:32350107).
Together with ATAD5 and by regulating USP1 activity, has a role in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA (PubMed:20147293).
Together with ATAD5, has a role in recruiting RAD51 to stalled forks during replication stress (PubMed:31844045).
(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 TIP (PubMed:12196293).
In case of infection by papillomavirus HPV11, promotes the maintenance of the viral genome via its interaction with HPV11 helicase E1 (PubMed:18032488).

Biological Process cellular response to DNA damage stimulus Source:UniProtKB2 Publications
Biological Process double-strand break repair via homologous recombination Source:GO_Central1 Publication
Biological Process embryonic organ development Source:Ensembl
Biological Process homeostasis of number of cells Source:Ensembl
Biological Process multicellular organism growth Source:Ensembl
Biological Process positive regulation of double-strand break repair via homologous recombination Source:UniProtKB2 Publications
Biological Process positive regulation of epithelial cell proliferation Source:Ensembl
Biological Process protein deubiquitination Source:GO_Central1 Publication
Biological Process regulation of protein monoubiquitination Source:Ensembl
Biological Process seminiferous tubule development Source:Ensembl
Biological Process single fertilization Source:Ensembl
Biological Process skeletal system morphogenesis Source:Ensembl
Biological Process skin development Source:Ensembl
Biological Process spermatogenesis Source:Ensembl

Nucleus
Cytoplasm
Lysosome
Late endosome
Mainly in cytoplasmic compartments (PubMed:12196293, PubMed:18032488).
In case of infection by papillomavirus HPV11, translocates to the nucleus via its interaction with papillomavirus HPV11 (PubMed:18032488).