DegronMD - Q8TAF3(WDR48)

FUNCTION: 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). {ECO:0000269|PubMed:18082604, ECO:0000269|PubMed:19075014, ECO:0000269|PubMed:24145035, ECO:0000269|PubMed:26388029, ECO:0000269|PubMed:27239033, ECO:0000269|PubMed:27373336, ECO:0000269|PubMed:27463890, ECO:0000269|PubMed:27650958, ECO:0000269|PubMed:31253762, ECO:0000269|PubMed:32350107}.; FUNCTION: (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). {ECO:0000269|PubMed:12196293, ECO:0000269|PubMed:18032488}. View more >>

GO - Biological processes (BP): View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.E536D	TCGA-AP-A1DK	UCEC	TCGA	DSGGET	DEG_SCF_TRCP1_1	532:537	Mutation altering degron motif	0.5647
p.S533Y	TCGA-B5-A3FA	UCEC	TCGA	DSGGET	DEG_SCF_TRCP1_1	532:537	Mutation altering degron motif	0.712
p.R523C	TCGA-EE-A29S	SKCM	TCGA	DSGGET	DEG_SCF_TRCP1_1	532:537	Mutation rewiring degron network	0.0833
p.R531L	TCGA-L5-A4OJ	ESCA	TCGA	DSGGET	DEG_SCF_TRCP1_1	532:537	Mutation rewiring degron network	0.3056
p.M540L	SIDM01175	Other Sarcomas	GDSC	DSGGET	DEG_SCF_TRCP1_1	532:537	Mutation rewiring degron network	0.25
p.M540L	ACH-002309	Sarcoma	CCLE	DSGGET	DEG_SCF_TRCP1_1	532:537	Mutation rewiring degron network	0.25
p.M540L	SW684	soft tissue	COSMIC	DSGGET	DEG_SCF_TRCP1_1	532:537	Mutation rewiring degron network	0.25
p.E538Q	SIDM00688	B-Cell Non-Hodgkin's Lymphoma	GDSC	DSGGET	DEG_SCF_TRCP1_1	532:537	Mutation rewiring degron network	0.3056
p.E538Q	ACH-002253	Lymphoma	CCLE	DSGGET	DEG_SCF_TRCP1_1	532:537	Mutation rewiring degron network	0.3056
p.E538Q	JSC-1	haematopoietic and lymphoid tissue	COSMIC	DSGGET	DEG_SCF_TRCP1_1	532:537	Mutation rewiring degron network	0.3056

DegronMD: protein-targeted degradation, mutation and drug response to degrons

WDR48

UniProt ID: Q8TAF3

Entrez ID: 57599

Protein name: WD repeat-containing protein 48 (USP1-associated factor 1) (WD repeat endosomal protein) (p80)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for WDR48 in