UniProt functional annotation for Q8TAF3



	UniProt functional annotation for Q8TAF3

UniProt code: Q8TAF3.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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}.

Subunit: Interacts with USP46 (PubMed:19075014, PubMed:26388029). Interacts with USP1 (PubMed:18082604, PubMed:26388029). Interacts with USP12 (PubMed:19075014, PubMed:27650958, PubMed:27373336). Component of the USP12-WDR20-WDR48 deubiquitinating complex (PubMed:27373336). Interacts with PHLPP1 (PubMed:24145035). Interacts with RAD51AP1; the interaction is direct and promotes formation of a trimeric complex with RAD51 via RAD51AP1 (PubMed:27463890, PubMed:27239033). {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}.

Subunit: (Microbial infection) Interacts with papillomavirus HPV11 E1 protein. {ECO:0000269|PubMed:18032488}.

Subunit: (Microbial infection) Interacts with Saimiriine herpesvirus TIP protein. {ECO:0000269|PubMed:12196293, ECO:0000269|PubMed:12885920}.

Subcellular location: Nucleus {ECO:0000269|PubMed:18032488}. Cytoplasm {ECO:0000269|PubMed:12196293, ECO:0000269|PubMed:18032488}. Lysosome {ECO:0000269|PubMed:12196293}. Late endosome {ECO:0000269|PubMed:12196293}. Note=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). {ECO:0000269|PubMed:12196293, ECO:0000269|PubMed:18032488}.

Tissue specificity: Ubiquitous. {ECO:0000269|PubMed:12196293}.

Domain: N-terminal WD region interacts with TIP and C-terminal region mediates lysosomal localization (Probable). The WD repeats are required for the interaction with deubiquitinating enzymes USP1, USP12 and USP46. {ECO:0000269|PubMed:26388029, ECO:0000305}.

Miscellaneous: Knockdown of WDR48 increases Akt activation. {ECO:0000269|PubMed:24145035}.

Similarity: Belongs to the WD repeat WDR48 family. {ECO:0000305}.

Sequence caution: Sequence=AAH37168.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAA95973.2; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAH56182.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAH56300.1; Type=Erroneous initiation; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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}.


Subunit:		Interacts with USP46 (PubMed:19075014, PubMed:26388029). Interacts with USP1 (PubMed:18082604, PubMed:26388029). Interacts with USP12 (PubMed:19075014, PubMed:27650958, PubMed:27373336). Component of the USP12-WDR20-WDR48 deubiquitinating complex (PubMed:27373336). Interacts with PHLPP1 (PubMed:24145035). Interacts with RAD51AP1; the interaction is direct and promotes formation of a trimeric complex with RAD51 via RAD51AP1 (PubMed:27463890, PubMed:27239033). {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}.
Subunit:		(Microbial infection) Interacts with papillomavirus HPV11 E1 protein. {ECO:0000269\|PubMed:18032488}.
Subunit:		(Microbial infection) Interacts with Saimiriine herpesvirus TIP protein. {ECO:0000269\|PubMed:12196293, ECO:0000269\|PubMed:12885920}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:18032488}. Cytoplasm {ECO:0000269\|PubMed:12196293, ECO:0000269\|PubMed:18032488}. Lysosome {ECO:0000269\|PubMed:12196293}. Late endosome {ECO:0000269\|PubMed:12196293}. Note=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). {ECO:0000269\|PubMed:12196293, ECO:0000269\|PubMed:18032488}.
Tissue specificity:		Ubiquitous. {ECO:0000269\|PubMed:12196293}.
Domain:		N-terminal WD region interacts with TIP and C-terminal region mediates lysosomal localization (Probable). The WD repeats are required for the interaction with deubiquitinating enzymes USP1, USP12 and USP46. {ECO:0000269\|PubMed:26388029, ECO:0000305}.
Miscellaneous:		Knockdown of WDR48 increases Akt activation. {ECO:0000269\|PubMed:24145035}.
Similarity:		Belongs to the WD repeat WDR48 family. {ECO:0000305}.
Sequence caution:		Sequence=AAH37168.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAA95973.2; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAH56182.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAH56300.1; Type=Erroneous initiation; Evidence={ECO:0000305};