ID MEP50_MOUSE Reviewed; 342 AA.
AC Q99J09; Q3TFJ1; Q8BSH8; Q9CZY5;
DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 24-JAN-2024, entry version 159.
DE RecName: Full=Methylosome protein WDR77 {ECO:0000305};
DE AltName: Full=Methylosome protein 50 {ECO:0000250|UniProtKB:Q9BQA1};
DE Short=MEP-50 {ECO:0000250|UniProtKB:Q9BQA1};
DE AltName: Full=WD repeat-containing protein 77 {ECO:0000312|MGI:MGI:1917715};
GN Name=Wdr77 {ECO:0000312|MGI:MGI:1917715};
GN Synonyms=Mep50 {ECO:0000312|MGI:MGI:1917715};
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].
RC STRAIN=C57BL/6J; TISSUE=Amnion, Embryo, Head, Liver, and Mesonephros;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor;
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 [3]
RP INTERACTION WITH SUZ12.
RX PubMed=16712789; DOI=10.1016/j.bbrc.2006.05.014;
RA Furuno K., Masatsugu T., Sonoda M., Sasazuki T., Yamamoto K.;
RT "Association of Polycomb group SUZ12 with WD-repeat protein MEP50 that
RT binds to histone H2A selectively in vitro.";
RL Biochem. Biophys. Res. Commun. 345:1051-1058(2006).
RN [4]
RP FUNCTION IN METHYLATION OF PIWI PROTEINS.
RX PubMed=19584108; DOI=10.1101/gad.1814809;
RA Vagin V.V., Wohlschlegel J., Qu J., Jonsson Z., Huang X., Chuma S.,
RA Girard A., Sachidanandam R., Hannon G.J., Aravin A.A.;
RT "Proteomic analysis of murine Piwi proteins reveals a role for arginine
RT methylation in specifying interaction with Tudor family members.";
RL Genes Dev. 23:1749-1762(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-5, AND IDENTIFICATION BY MASS
RP 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 [6]
RP FUNCTION, PATHWAY, AND IDENTIFICATION IN THE DCX(WDR77) COMPLEX.
RX PubMed=35197566; DOI=10.1038/s41418-022-00954-9;
RA Fan Y., Huo X., Guo B., Zhang X., Yang Y., Lian J., Meng X., Shao Y.,
RA Zou Y., Guo H., Wang H., Sun G., Dou H., Wang J., Shao C., Gong Y., Hu H.;
RT "Cullin 4b-RING ubiquitin ligase targets IRGM1 to regulate Wnt signaling
RT and intestinal homeostasis.";
RL Cell Death Differ. 29:1673-1688(2022).
CC -!- FUNCTION: Non-catalytic component of the methylosome complex, composed
CC of PRMT5, WDR77 and CLNS1A, which modifies specific arginines to
CC dimethylarginines in several spliceosomal Sm proteins and histones (By
CC similarity). This modification targets Sm proteins to the survival of
CC motor neurons (SMN) complex for assembly into small nuclear
CC ribonucleoprotein core particles (By similarity). Might play a role in
CC transcription regulation (By similarity). The methylosome complex also
CC methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation
CC of Piwi proteins being required for the interaction with Tudor domain-
CC containing proteins and subsequent localization to the meiotic nuage
CC (PubMed:19584108). {ECO:0000250|UniProtKB:Q9BQA1,
CC ECO:0000269|PubMed:19584108}.
CC -!- FUNCTION: Substrate-recognition component of the DCX(WDR77) complex,
CC which mediates ubiquitination and degradation of Irgm1 in intestinal
CC cells. {ECO:0000269|PubMed:35197566}.
CC -!- SUBUNIT: Component of the methylosome complex composed of PRMT5, WDR77
CC and CLNS1A (By similarity). Found in a complex composed of PRMT5, WDR77
CC and RIOK1 (By similarity). RIOK1 and CLNS1A bound directly to PRMT5 at
CC the same binding site, in a mutually exclusive manner, which allows the
CC recruitment of distinct methylation substrates, such as nucleolin/NCL
CC and Sm proteins, respectively (By similarity). Found in a complex with
CC the component of the methylosome, PRMT5, CLNS1A, WDR77, PRMT1 and ERH
CC (By similarity). Directly interacts with PRMT5, as well as with several
CC Sm proteins, including SNRPB and SNRPD2 and, more weakly, SNRPD3 and
CC SNRPE (By similarity). Forms a compact hetero-octamer with PRMT5,
CC decorating the outer surface of a PRMT5 tetramer (By similarity).
CC Interacts with SUZ12 and histone H2A/H2AC20, but not with histones H2B,
CC H3 nor H4 (PubMed:16712789). Interacts with CTDP1 and LSM11 (By
CC similarity). Interacts with APEX1, AR and NKX3-1 (By similarity).
CC Interacts with CHTOP (By similarity). Interacts with FAM47E (By
CC similarity). Component of the DCX(WDR77) complex, composed of Cul4b,
CC Ddb1, Wdr77 and Rbx1 (PubMed:35197566). Interacts with TSC22D2 (By
CC similarity). {ECO:0000250|UniProtKB:Q9BQA1,
CC ECO:0000269|PubMed:16712789, ECO:0000269|PubMed:35197566}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9BQA1}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9BQA1}.
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DR EMBL; AK012014; BAB27975.1; -; mRNA.
DR EMBL; AK032897; BAC28076.1; -; mRNA.
DR EMBL; AK048488; BAC33350.1; -; mRNA.
DR EMBL; AK050391; BAC34232.1; -; mRNA.
DR EMBL; AK163839; BAE37512.1; -; mRNA.
DR EMBL; AK169128; BAE40907.1; -; mRNA.
DR EMBL; BC005755; AAH05755.1; -; mRNA.
DR CCDS; CCDS17715.1; -.
DR RefSeq; NP_081708.1; NM_027432.3.
DR AlphaFoldDB; Q99J09; -.
DR SMR; Q99J09; -.
DR BioGRID; 214072; 24.
DR ComplexPortal; CPX-1023; Methylosome.
DR IntAct; Q99J09; 6.
DR MINT; Q99J09; -.
DR STRING; 10090.ENSMUSP00000010278; -.
DR GlyGen; Q99J09; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q99J09; -.
DR PhosphoSitePlus; Q99J09; -.
DR SwissPalm; Q99J09; -.
DR EPD; Q99J09; -.
DR jPOST; Q99J09; -.
DR MaxQB; Q99J09; -.
DR PaxDb; 10090-ENSMUSP00000010278; -.
DR PeptideAtlas; Q99J09; -.
DR ProteomicsDB; 295543; -.
DR Pumba; Q99J09; -.
DR Antibodypedia; 35257; 336 antibodies from 33 providers.
DR Ensembl; ENSMUST00000010278.12; ENSMUSP00000010278.6; ENSMUSG00000000561.15.
DR GeneID; 70465; -.
DR KEGG; mmu:70465; -.
DR UCSC; uc008qvo.1; mouse.
DR AGR; MGI:1917715; -.
DR CTD; 79084; -.
DR MGI; MGI:1917715; Wdr77.
DR VEuPathDB; HostDB:ENSMUSG00000000561; -.
DR eggNOG; KOG0284; Eukaryota.
DR GeneTree; ENSGT00390000010711; -.
DR HOGENOM; CLU_051285_0_0_1; -.
DR InParanoid; Q99J09; -.
DR OMA; QMGCNAS; -.
DR OrthoDB; 810251at2759; -.
DR PhylomeDB; Q99J09; -.
DR TreeFam; TF325967; -.
DR Reactome; R-MMU-191859; snRNP Assembly.
DR Reactome; R-MMU-3214858; RMTs methylate histone arginines.
DR BioGRID-ORCS; 70465; 31 hits in 81 CRISPR screens.
DR ChiTaRS; Wdr77; mouse.
DR PRO; PR:Q99J09; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q99J09; Protein.
DR Bgee; ENSMUSG00000000561; Expressed in primitive streak and 273 other cell types or tissues.
DR ExpressionAtlas; Q99J09; baseline and differential.
DR Genevisible; Q99J09; MM.
DR GO; GO:0031465; C:Cul4B-RING E3 ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0034709; C:methylosome; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0008327; F:methyl-CpG binding; ISS:UniProtKB.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; ISO:MGI.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IDA:UniProtKB.
DR GO; GO:0060767; P:epithelial cell proliferation involved in prostate gland development; IMP:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0060770; P:negative regulation of epithelial cell proliferation involved in prostate gland development; IMP:MGI.
DR GO; GO:0007309; P:oocyte axis specification; IBA:GO_Central.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0048026; P:positive regulation of mRNA splicing, via spliceosome; NAS:ComplexPortal.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0060528; P:secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development; IMP:MGI.
DR GO; GO:0000387; P:spliceosomal snRNP assembly; NAS:ComplexPortal.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR001680; WD40_rpt.
DR PANTHER; PTHR46853; METHYLOSOME PROTEIN 50; 1.
DR PANTHER; PTHR46853:SF3; METHYLOSOME PROTEIN 50; 1.
DR Pfam; PF00400; WD40; 2.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50978; WD40 repeat-like; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 2.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Ubl conjugation pathway; WD repeat.
FT CHAIN 1..342
FT /note="Methylosome protein WDR77"
FT /id="PRO_0000051075"
FT REPEAT 22..75
FT /note="WD 1"
FT REPEAT 78..116
FT /note="WD 2"
FT REPEAT 123..162
FT /note="WD 3"
FT REPEAT 165..205
FT /note="WD 4"
FT REPEAT 209..250
FT /note="WD 5"
FT REPEAT 253..293
FT /note="WD 6"
FT REPEAT 295..330
FT /note="WD 7"
FT MOD_RES 5
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 267..285
FT /note="SVPLLTSLSEDCSLAVLDS -> RCCVSPGTWKGWVGTVVKE (in Ref.
FT 2; AAH05755)"
FT /evidence="ECO:0000305"
FT CONFLICT 286..342
FT /note="Missing (in Ref. 2; AAH05755)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 342 AA; 36943 MW; E9C52BC4D6E5AC36 CRC64;
MRKDTPPPLV PPAAREWNLP PNAPACMERQ LEAARYRSDG SLLLGVSSLS GRCWVGSLWF
FKDPSAAPNE GFCSAGVQTE AGVADLTWVG DKGILVASDS GAVELWELDE NETLIVSKFC
KYEHDDIVST VTVLSSGTQA VSGSKDCCIK IWDLAQQVSL NSYRAHAGQV TCVAASPHKD
SVFLSCSEDS RILLWDTRCP KPASQMACNA SGYLPTALAW HPQQSEVFVF GDENGSVSLV
DTKNASCTLS SAVHSQGVTR LVFSPHSVPL LTSLSEDCSL AVLDSSLSEV FRSRAHRDFV
RDATWSPLNH SLLTTVGWDH QVIHHVVPLE PLPNPGPDSV VE
//
