ID   WDR48_MACFA             Reviewed;         622 AA.
AC   Q4R2Z6;
DT   20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2005, sequence version 1.
DT   03-AUG-2022, entry version 75.
DE   RecName: Full=WD repeat-containing protein 48;
DE   AltName: Full=USP1-associated factor 1;
GN   Name=WDR48; Synonyms=UAF1; ORFNames=QtsA-20837;
OS   Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9541;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
RG   International consortium for macaque cDNA sequencing and analysis;
RT   "DNA sequences of macaque genes expressed in brain or testis and its
RT   evolutionary implications.";
RL   Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Regulator of deubiquitinating complexes, which acts as a
CC       strong activator of USP1, USP12 and USP46. Enhances the USP1-mediated
CC       deubiquitination of FANCD2; USP1 being almost inactive by itself.
CC       Activates deubiquitination by increasing the catalytic turnover without
CC       increasing the affinity of deubiquitinating enzymes for the substrate.
CC       Also activates deubiquitinating activity of complexes containing USP12.
CC       Docks at the distal end of the USP12 fingers domain and induces a
CC       cascade of structural changes leading to the activation of the enzyme.
CC       Together with RAD51AP1, promotes DNA repair by stimulating RAD51-
CC       mediated homologous recombination. Binds single-stranded DNA (ssDNA)
CC       and double-stranded DNA (dsDNA). DNA-binding is required both for USP1-
CC       mediated deubiquitination of FANCD2 and stimulation of RAD51-mediated
CC       homologous recombination: both WDR48/UAF1 and RAD51AP1 have coordinated
CC       role in DNA-binding during these processes.Together with ATAD5 and by
CC       regulating USP1 activity, has a role in PCNA-mediated translesion
CC       synthesis (TLS) by deubiquitinating monoubiquitinated PCNA. Together
CC       with ATAD5, has a role in recruiting RAD51 to stalled forks during
CC       replication stress. {ECO:0000250|UniProtKB:Q8TAF3}.
CC   -!- SUBUNIT: Interacts with USP46. Interacts with USP1. Interacts with
CC       USP12. Component of the USP12-WDR20-WDR48 deubiquitinating complex.
CC       Interacts with PHLPP1. Interacts with RAD51AP1; the interaction is
CC       direct and promotes formation of a trimeric complex with RAD51 via
CC       RAD51AP1. Interacts with ATAD5; the interaction regulates USP1-mediated
CC       PCNA deubiquitination. Interacts with RAD51; the interaction is
CC       enhanced under replication stress. {ECO:0000250|UniProtKB:Q8TAF3}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8TAF3}. Cytoplasm
CC       {ECO:0000250|UniProtKB:Q8TAF3}. Lysosome
CC       {ECO:0000250|UniProtKB:Q8TAF3}. Late endosome
CC       {ECO:0000250|UniProtKB:Q8TAF3}. Note=Mainly in cytoplasmic
CC       compartments. {ECO:0000250|UniProtKB:Q8TAF3}.
CC   -!- DOMAIN: The WD repeats are required for the interaction with
CC       deubiquitinating enzymes USP1, USP12 and USP46.
CC       {ECO:0000250|UniProtKB:Q8TAF3}.
CC   -!- SIMILARITY: Belongs to the WD repeat WDR48 family. {ECO:0000305}.
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DR   EMBL; AB179472; BAE02523.1; -; mRNA.
DR   AlphaFoldDB; Q4R2Z6; -.
DR   SMR; Q4R2Z6; -.
DR   STRING; 9541.XP_005546756.1; -.
DR   Proteomes; UP000233100; Unplaced.
DR   GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0035800; F:deubiquitinase activator activity; ISS:UniProtKB.
DR   GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR   GO; GO:0003690; F:double-stranded DNA binding; ISS:UniProtKB.
DR   GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
DR   GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR   GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR   GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR   Gene3D; 2.130.10.10; -; 2.
DR   InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR   InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR   InterPro; IPR001680; WD40_repeat.
DR   InterPro; IPR019775; WD40_repeat_CS.
DR   InterPro; IPR036322; WD40_repeat_dom_sf.
DR   InterPro; IPR021772; WDR48/Bun107.
DR   Pfam; PF11816; DUF3337; 1.
DR   Pfam; PF00400; WD40; 4.
DR   PRINTS; PR00320; GPROTEINBRPT.
DR   SMART; SM00320; WD40; 6.
DR   SUPFAM; SSF50978; SSF50978; 1.
DR   PROSITE; PS00678; WD_REPEATS_1; 2.
DR   PROSITE; PS50082; WD_REPEATS_2; 5.
DR   PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE   2: Evidence at transcript level;
KW   Acetylation; Cytoplasm; DNA damage; DNA repair; DNA-binding; Endosome;
KW   Lysosome; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW   Ubl conjugation pathway; WD repeat.
FT   CHAIN           1..622
FT                   /note="WD repeat-containing protein 48"
FT                   /id="PRO_0000051400"
FT   REPEAT          28..67
FT                   /note="WD 1"
FT   REPEAT          73..112
FT                   /note="WD 2"
FT   REPEAT          115..154
FT                   /note="WD 3"
FT   REPEAT          166..205
FT                   /note="WD 4"
FT   REPEAT          208..247
FT                   /note="WD 5"
FT   REPEAT          250..289
FT                   /note="WD 6"
FT   REPEAT          292..334
FT                   /note="WD 7"
FT   REPEAT          358..397
FT                   /note="WD 8"
FT   REGION          552..573
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         28
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BH57"
FT   MOD_RES         214
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TAF3"
FT   MOD_RES         523
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BH57"
FT   MOD_RES         558
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TAF3"
SQ   SEQUENCE   622 AA;  69867 MW;  52F8FCDD22F8BA47 CRC64;
     MAAHHRQNTA GRRKVQVSYV IRDEVEKYNR NGVNALQLDP ALNRLFTAGR DSIIRIWSVN
     QHKQDPYIAS MEHHTDWVND IVLCCNGKTL ISASSDTTVK VWNAHKGFCM STLRTHKDYV
     KALAYAKDKE LVASAGLDRQ IFLWDVNTLT ALTASNNTVT TSSLSGNKDS IYSLAMNQLG
     TIIVSGSTEK VLRVWDPRTC AKLMKLKGHT DNVKALLLNR DGTQCLSGSS DGTIRLWSLG
     QQRCIATYRV HDEGVWALQV NDAFTHVYSG GRDRKIYCTD LRNPDIRVLI CEEKAPVLKM
     ELDRSADPPP AIWVATTKST VNKWTLKGIH NFRASGDYDN DCTNPITPLC TQPDQVIKGG
     ASIIQCHILN DKRHILTKDT NNNVAYWVSV KDAGFSSPDG SDPKLNLGGL LLQALLEYWP
     RTHVNPMDEE ENEVNHVNGE QENRVQKGNG YFQVPPHTPV IFGEAGGRTL FRLLCRDSGG
     ETESMLLNET VPQWVIDITV DKNMPKFNKI PFYLQPHASS GAKTLKKDRL SASDMLQVRK
     VMEHVYEKII NLDNESQTTS SSNNEKPGEQ EKEEDIAVLA EEKIELLCQD QVLDPNMDLR
     TVKHFIWKSG GDLTLHYRQK ST