MEP50_MOUSE
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 03-AUG-2022, entry version 151.
DE RecName: Full=Methylosome protein 50;
DE Short=MEP-50;
DE AltName: Full=WD repeat-containing protein 77;
GN Name=Wdr77; Synonyms=Mep50;
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).
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.
CC This modification targets Sm proteins to the survival of motor neurons
CC (SMN) complex for assembly into small nuclear ribonucleoprotein core
CC particles. Might play a role in transcription regulation. The
CC methylosome complex also methylates the Piwi proteins (PIWIL1, PIWIL2
CC and PIWIL4), methylation of Piwi proteins being required for the
CC interaction with Tudor domain-containing proteins and subsequent
CC localization to the meiotic nuage (PubMed:19584108).
CC {ECO:0000250|UniProtKB:Q9BQA1, ECO:0000269|PubMed:19584108}.
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 Directly interacts with PRMT5, as well as with several Sm proteins,
CC including SNRPB and SNRPD2 and, more weakly, SNRPD3 and SNRPE. Forms a
CC compact hetero-octamer with PRMT5, decorating the outer surface of a
CC PRMT5 tetramer. Interacts with SUZ12 and histone H2A/H2AC20, but not
CC with histones H2B, H3 nor H4 (PubMed:16712789). Interacts with CTDP1
CC and LSM11. Interacts with APEX1, AR and NKX3-1. Interacts with CHTOP.
CC Interacts with FAM47E. {ECO:0000250|UniProtKB:Q9BQA1,
CC ECO:0000269|PubMed:16712789}.
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 iPTMnet; Q99J09; -.
DR PhosphoSitePlus; Q99J09; -.
DR EPD; Q99J09; -.
DR jPOST; Q99J09; -.
DR MaxQB; Q99J09; -.
DR PaxDb; Q99J09; -.
DR PeptideAtlas; Q99J09; -.
DR PRIDE; Q99J09; -.
DR ProteomicsDB; 295543; -.
DR Antibodypedia; 35257; 291 antibodies from 33 providers.
DR Ensembl; ENSMUST00000010278; ENSMUSP00000010278; ENSMUSG00000000561.
DR GeneID; 70465; -.
DR KEGG; mmu:70465; -.
DR UCSC; uc008qvo.1; mouse.
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; CVTRLVF; -.
DR OrthoDB; 774546at2759; -.
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; 30 hits in 75 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 269 other tissues.
DR ExpressionAtlas; Q99J09; baseline and differential.
DR Genevisible; Q99J09; MM.
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:0060767; P:epithelial cell proliferation involved in prostate gland development; IMP:MGI.
DR GO; GO:0043985; P:histone H4-R3 methylation; IC:ComplexPortal.
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; IC:ComplexPortal.
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; IC:ComplexPortal.
DR Gene3D; 2.130.10.10; -; 1.
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 Pfam; PF00400; WD40; 2.
DR SMART; SM00320; WD40; 6.
DR SUPFAM; SSF50978; SSF50978; 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; WD repeat.
FT CHAIN 1..342
FT /note="Methylosome protein 50"
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
