Gene name: WDR48

Uniprot entry:

Q8TAF3

Protein names:

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

Protein sequence:

1_MAAHH 6_ RQNTA 11_ GRRKV 16_ QVSYV 21_ IRDEV 26_ EKYNR 31_ NGVNA 36_ LQLDP 41_ ALNRL 46_ FTAGR 51_ DSIIR 56_ IWSVN 61_ QHKQD 66_ PYIAS 71_ MEHHT 76_ DWVND 81_ IVLCC 86_ NGKTL 91_ ISASS 96_ DTTVK 101_ VWNAH 106_ KGFCM 111_ STLRT 116_ HKDYV 121_ KALAY 126_ AKDKE 131_ LVASA 136_ GLDRQ 141_ IFLWD 146_ VNTLT 151_ ALTAS 156_ NNTVT 161_ TSSLS 166_ GNKDS 171_ IYSLA 176_ MNQLG 181_ TIIVS 186_ GSTEK 191_ VLRVW 196_ DPRTC 201_ AKLMK 206_ LKGHT 211_ DNVKA 216_ LLLNR 221_ DGTQC 226_ LSGSS 231_ DGTIR 236_ LWSLG 241_ QQRCI 246_ ATYRV 251_ HDEGV 256_ WALQV 261_ NDAFT 266_ HVYSG 271_ GRDRK 276_ IYCTD 281_ LRNPD 286_ IRVLI 291_ CEEKA 296_ PVLKM 301_ ELDRS 306_ ADPPP 311_ AIWVA 316_ TTKST 321_ VNKWT 326_ LKGIH 331_ NFRAS 336_ GDYDN 341_ DCTNP 346_ ITPLC 351_ TQPDQ 356_ VIKGG 361_ ASIIQ 366_ CHILN 371_ DKRHI 376_ LTKDT 381_ NNNVA 386_ YWDVL 391_ KACKV 396_ EDLGK 401_ VDFED 406_ EIKKR 411_ FKMVY 416_ VPNWF 421_ SVDLK 426_ TGMLT 431_ ITLDE 436_ SDCFA 441_ AWVSA 446_ KDAGF 451_ SSPDG 456_ SDPKL 461_ NLGGL 466_ LLQAL 471_ LEYWP 476_ RTHVN 481_ PMDEE 486_ ENEVN 491_ HVNGE 496_ QENRV 501_ QKGNG 506_ YFQVP 511_ PHTPV 516_ IFGEA 521_ GGRTL 526_ FRLLC 531_ RDSGG 536_ ETESM 541_ LLNET 546_ VPQWV 551_ IDITV 556_ DKNMP 561_ KFNKI 566_ PFYLQ 571_ PHASS 576_ GAKTL 581_ KKDRL 586_ SASDM 591_ LQVRK 596_ VMEHV 601_ YEKII 606_ NLDNE 611_ SQTTS 616_ SSNNE 621_ KPGEQ 626_ EKEED 631_ IAVLA 636_ EEKIE 641_ LLCQD 646_ QVLDP 651_ NMDLR 656_ TVKHF 661_ IWKSG 666_ GDLTL 671_HYRQK

Protein annotations

Protein functions:

1: Regulator of deubiquitinating complexes, which acts as a strong activator of USP1, USP12 and USP46 (PubMed:18082604, PubMed:19075014, PubMed:26388029, PubMed:31253762). 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:27373336, PubMed:27650958). 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:27373336, PubMed:27650958). Together with RAD51AP1, promotes DNA repair by stimulating RAD51-mediated homologous recombination (PubMed:27239033, PubMed:27463890, 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)

2: (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)