| IED ID | IndEnz0002012155 |
| Enzyme Type ID | protease012155 |
| Protein Name |
WD repeat-containing protein 48 USP1-associated factor 1 WD repeat endosomal protein p80 |
| Gene Name | WDR48 KIAA1449 UAF1 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MAAHHRQNTAGRRKVQVSYVIRDEVEKYNRNGVNALQLDPALNRLFTAGRDSIIRIWSVNQHKQDPYIASMEHHTDWVNDIVLCCNGKTLISASSDTTVKVWNAHKGFCMSTLRTHKDYVKALAYAKDKELVASAGLDRQIFLWDVNTLTALTASNNTVTTSSLSGNKDSIYSLAMNQLGTIIVSGSTEKVLRVWDPRTCAKLMKLKGHTDNVKALLLNRDGTQCLSGSSDGTIRLWSLGQQRCIATYRVHDEGVWALQVNDAFTHVYSGGRDRKIYCTDLRNPDIRVLICEEKAPVLKMELDRSADPPPAIWVATTKSTVNKWTLKGIHNFRASGDYDNDCTNPITPLCTQPDQVIKGGASIIQCHILNDKRHILTKDTNNNVAYWDVLKACKVEDLGKVDFEDEIKKRFKMVYVPNWFSVDLKTGMLTITLDESDCFAAWVSAKDAGFSSPDGSDPKLNLGGLLLQALLEYWPRTHVNPMDEEENEVNHVNGEQENRVQKGNGYFQVPPHTPVIFGEAGGRTLFRLLCRDSGGETESMLLNETVPQWVIDITVDKNMPKFNKIPFYLQPHASSGAKTLKKDRLSASDMLQVRKVMEHVYEKIINLDNESQTTSSSNNEKPGEQEKEEDIAVLAEEKIELLCQDQVLDPNMDLRTVKHFIWKSGGDLTLHYRQKST |
| Enzyme Length | 677 |
| Uniprot Accession Number | Q8TAF3 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | 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}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (6); Beta strand (49); Chain (1); Erroneous initiation (4); Helix (12); Modified residue (4); Mutagenesis (23); Natural variant (1); Region (1); Repeat (8); Sequence conflict (5); Turn (9) |
| Keywords | 3D-structure;Acetylation;Alternative splicing;Cytoplasm;DNA damage;DNA repair;DNA-binding;Endosome;Host-virus interaction;Lysosome;Nucleus;Phosphoprotein;Reference proteome;Repeat;Ubl conjugation pathway;WD repeat |
| Interact With | O94782 |
| Induction | |
| Subcellular Location | 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}. |
| Modified Residue | MOD_RES 28; /note=Phosphotyrosine; /evidence=ECO:0000250|UniProtKB:Q8BH57; MOD_RES 214; /note=N6-acetyllysine; /evidence=ECO:0007744|PubMed:19608861; MOD_RES 578; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:Q8BH57; MOD_RES 613; /note=Phosphothreonine; /evidence=ECO:0007744|PubMed:24275569 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | Electron microscopy (1); X-ray crystallography (11) |
| Cross Reference PDB | 5CVL; 5CVN; 5CVO; 5K1A; 5K1B; 5K1C; 5L8E; 5L8W; 6JLQ; 7AY0; 7AY1; 7AY2; |
| Mapped Pubmed ID | 12660384; 14556779; 15572677; 16531995; 16690743; 17353931; 19210352; 19596236; 19615732; 20085582; 20147737; 20385554; 20501646; 20562859; 20603015; 20603016; 20603073; 20671156; 20889717; 21464321; 22278251; 22575643; 22692201; 22701671; 23116119; 24056413; 24076221; 24850727; 25500724; 26758085; 27170215; 28010895; 28302046; 29138248; 30890612; 31632687; 32594826; 33461373; 33795880; |
| Motif | |
| Gene Encoded By | |
| Mass | 76,210 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |