WDR48_MOUSE
ID WDR48_MOUSE Reviewed; 676 AA.
AC Q8BH57; Q80TD4; Q80XI0; Q8BRM0; Q8CBK0; Q922Z9; Q9CRR1; Q9CSL0;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=WD repeat-containing protein 48;
DE AltName: Full=USP1-associated factor 1;
GN Name=Wdr48; Synonyms=Kiaa1449, Uaf1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [2]
RP SEQUENCE REVISION.
RA Okazaki N., Kikuno R., Nagase T., Ohara O., Koga H.;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=C57BL/6J;
RC TISSUE=Brain cortex, Cecum, Cerebellum, Lung, Testis, and Urinary bladder;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-28, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-578, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8BH57-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BH57-2; Sequence=VSP_016778;
CC Name=3;
CC IsoId=Q8BH57-3; Sequence=VSP_016779, VSP_016780;
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC65793.3; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK122511; BAC65793.3; ALT_INIT; mRNA.
DR EMBL; AK012599; BAB28345.1; -; mRNA.
DR EMBL; AK018396; BAB31193.3; ALT_TERM; mRNA.
DR EMBL; AK030041; BAC26755.1; -; mRNA.
DR EMBL; AK033631; BAC28400.1; -; mRNA.
DR EMBL; AK035273; BAC29010.1; -; mRNA.
DR EMBL; AK035864; BAC29218.1; -; mRNA.
DR EMBL; AK043970; BAC31719.1; -; mRNA.
DR EMBL; BC006679; AAH06679.1; -; mRNA.
DR EMBL; BC048155; AAH48155.1; -; mRNA.
DR EMBL; BC062967; AAH62967.1; -; mRNA.
DR CCDS; CCDS23618.1; -. [Q8BH57-1]
DR RefSeq; NP_080512.1; NM_026236.3. [Q8BH57-1]
DR AlphaFoldDB; Q8BH57; -.
DR SMR; Q8BH57; -.
DR BioGRID; 212277; 65.
DR IntAct; Q8BH57; 24.
DR MINT; Q8BH57; -.
DR STRING; 10090.ENSMUSP00000042509; -.
DR iPTMnet; Q8BH57; -.
DR PhosphoSitePlus; Q8BH57; -.
DR SwissPalm; Q8BH57; -.
DR EPD; Q8BH57; -.
DR jPOST; Q8BH57; -.
DR MaxQB; Q8BH57; -.
DR PaxDb; Q8BH57; -.
DR PeptideAtlas; Q8BH57; -.
DR PRIDE; Q8BH57; -.
DR ProteomicsDB; 275199; -. [Q8BH57-1]
DR ProteomicsDB; 275200; -. [Q8BH57-2]
DR ProteomicsDB; 275201; -. [Q8BH57-3]
DR Antibodypedia; 50460; 121 antibodies from 25 providers.
DR DNASU; 67561; -.
DR Ensembl; ENSMUST00000036561; ENSMUSP00000042509; ENSMUSG00000032512. [Q8BH57-1]
DR Ensembl; ENSMUST00000215307; ENSMUSP00000149478; ENSMUSG00000032512. [Q8BH57-2]
DR Ensembl; ENSMUST00000217472; ENSMUSP00000150321; ENSMUSG00000032512. [Q8BH57-3]
DR GeneID; 67561; -.
DR KEGG; mmu:67561; -.
DR UCSC; uc009sbm.1; mouse. [Q8BH57-3]
DR UCSC; uc009sbn.1; mouse. [Q8BH57-1]
DR UCSC; uc009sbo.1; mouse. [Q8BH57-2]
DR CTD; 57599; -.
DR MGI; MGI:1914811; Wdr48.
DR VEuPathDB; HostDB:ENSMUSG00000032512; -.
DR eggNOG; KOG0308; Eukaryota.
DR GeneTree; ENSGT00920000149157; -.
DR HOGENOM; CLU_014960_0_1_1; -.
DR InParanoid; Q8BH57; -.
DR OMA; NWFNVDL; -.
DR OrthoDB; 261328at2759; -.
DR PhylomeDB; Q8BH57; -.
DR TreeFam; TF315205; -.
DR Reactome; R-MMU-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-6783310; Fanconi Anemia Pathway.
DR BioGRID-ORCS; 67561; 23 hits in 113 CRISPR screens.
DR ChiTaRS; Wdr48; mouse.
DR PRO; PR:Q8BH57; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8BH57; protein.
DR Bgee; ENSMUSG00000032512; Expressed in spermatocyte and 255 other tissues.
DR ExpressionAtlas; Q8BH57; baseline and differential.
DR Genevisible; Q8BH57; MM.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
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:0043130; F:ubiquitin binding; IBA:GO_Central.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:MGI.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:MGI.
DR GO; GO:0048568; P:embryonic organ development; IMP:MGI.
DR GO; GO:0048872; P:homeostasis of number of cells; IMP:MGI.
DR GO; GO:0008584; P:male gonad development; IMP:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:1903003; P:positive regulation of protein deubiquitination; ISO:MGI.
DR GO; GO:0016579; P:protein deubiquitination; ISO:MGI.
DR GO; GO:1902525; P:regulation of protein monoubiquitination; IMP:MGI.
DR GO; GO:0072520; P:seminiferous tubule development; IMP:MGI.
DR GO; GO:0007338; P:single fertilization; IMP:MGI.
DR GO; GO:0048705; P:skeletal system morphogenesis; IMP:MGI.
DR GO; GO:0043588; P:skin development; IMP:MGI.
DR GO; GO:0007283; P:spermatogenesis; IMP:MGI.
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; 7.
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 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; DNA damage; DNA repair;
KW DNA-binding; Endosome; Lysosome; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Ubl conjugation pathway; WD repeat.
FT CHAIN 1..676
FT /note="WD repeat-containing protein 48"
FT /id="PRO_0000051401"
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 607..628
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 28
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT MOD_RES 214
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8TAF3"
FT MOD_RES 578
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 613
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8TAF3"
FT VAR_SEQ 414..427
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_016778"
FT VAR_SEQ 557..576
FT /note="KNMPKFNKIPFYLQPHASSG -> VSVLHSHFVLCFSQTLSLTL (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_016779"
FT VAR_SEQ 577..676
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_016780"
FT CONFLICT 85
FT /note="C -> S (in Ref. 3; BAC29218)"
FT /evidence="ECO:0000305"
FT CONFLICT 238
FT /note="S -> F (in Ref. 1; BAC65793)"
FT /evidence="ECO:0000305"
FT CONFLICT 642
FT /note="C -> W (in Ref. 3; BAC31719)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 676 AA; 76007 MW; 4996ED13D73DA235 CRC64;
MAAHHRQNTA GRRKVQVSYV IRDEVEKYNR NGVNALQLDP ALNRLFTAGR DSIIRIWSVN
QHKQDPYIAS MEHHTDWVND VVLCCNGKTL ISASSDTTVK VWNAHKGFCM STLRTHKDYV
KALAYAKDKE LVASAGLDRQ IFLWDVNTLT ALTASNNTVT TSSLSGNKDS IYSLAMNQLG
TIIVSGSTEK VLRVWDPRTC AKLMKLKGHT DNVKALLLHR DGTQCLSGSS DGTIRLWSLG
QQRCIATYRV HDEGVWALQV NDAFTHVYSG GRDRKIYCTD LRNPDIRVLI CEEKAPVLKM
ELDRSADPPP AIWVATTKST VNKWTLKGIH NFRASGDYDN DCTNPITPLC TQPDQVIKGG
ASIIQCHILN DKRHILTKDT NNNVAYWDVL KACKVEDLGK VDFEDEIKKR FKMVYVPNWF
SVDLKTGMLT ITLDESDCFA AWVSAKDAGF SSPDGSDPKL NLGGLLLQAL LEYWPRTHVT
PMDEEENEVN HVSGGQESRV QKGNGYFQVP PHTPVIFGEA GGRTLFRLLC RDSGGETEAM
LLNETVPQWV IDITVDKNMP KFNKIPFYLQ PHASSGAKTL KKDRLSASDM LQVRKVMEHV
YEKIINLDNE SQTTSSSNNE KPEQEKEEDI AVLAEEKIEL LCQDQVLDPN MDLRTVKHFI
WKSGGDLTLH YRQKST
