MEP50_HUMAN
ID MEP50_HUMAN Reviewed; 342 AA.
AC Q9BQA1; B3KMW6; B4DP38; Q3LID2; Q53FU2; Q6JZZ5; Q96GK4; Q9BWY3;
DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Methylosome protein 50;
DE Short=MEP-50;
DE AltName: Full=Androgen receptor cofactor p44;
DE AltName: Full=WD repeat-containing protein 77;
DE AltName: Full=p44/Mep50;
GN Name=WDR77; Synonyms=MEP50, WD45; ORFNames=HKMT1069, Nbla10071;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 4-15; 38-52;
RP 122-145; 151-164 AND 192-198, FUNCTION, INTERACTION WITH PRMT5; SNRPB;
RP SNRPD2; SNRPD3 AND SNRPE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=11756452; DOI=10.1074/jbc.m109984200;
RA Friesen W.J., Wyce A., Paushkin S., Abel L., Rappsilber J., Mann M.,
RA Dreyfuss G.;
RT "A novel WD repeat protein component of the methylosome binds Sm
RT proteins.";
RL J. Biol. Chem. 277:8243-8247(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 3-15, TISSUE
RP SPECIFICITY, AND INTERACTION WITH AR AND NKX3-1.
RX PubMed=12972618; DOI=10.1128/mcb.23.19.7019-7029.2003;
RA Hosohata K., Li P., Hosohata Y., Qin J., Roeder R.G., Wang Z.;
RT "Purification and identification of a novel complex which is involved in
RT androgen receptor-dependent transcription.";
RL Mol. Cell. Biol. 23:7019-7029(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney proximal tubule;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Hepatoblastoma;
RX PubMed=15221005; DOI=10.1038/sj.onc.1207782;
RA Yamada S., Ohira M., Horie H., Ando K., Takayasu H., Suzuki Y., Sugano S.,
RA Hirata T., Goto T., Matsunaga T., Hiyama E., Hayashi Y., Ando H., Suita S.,
RA Kaneko M., Sasaki F., Hashizume K., Ohnuma N., Nakagawara A.;
RT "Expression profiling and differential screening between hepatoblastomas
RT and the corresponding normal livers: identification of high expression of
RT the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas.";
RL Oncogene 23:5901-5911(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon, Lung, and Skin;
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 [8]
RP PROTEIN SEQUENCE OF 3-15; 36-52; 122-145; 151-179 AND 192-198,
RP PHOSPHORYLATION AT THR-5, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Zebisch A., Kolch W.;
RL Submitted (DEC-2008) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 184-342 (ISOFORM 1).
RC TISSUE=Neuroblastoma;
RX PubMed=12880961; DOI=10.1016/s0304-3835(03)00085-5;
RA Ohira M., Morohashi A., Nakamura Y., Isogai E., Furuya K., Hamano S.,
RA Machida T., Aoyama M., Fukumura M., Miyazaki K., Suzuki Y., Sugano S.,
RA Hirato J., Nakagawara A.;
RT "Neuroblastoma oligo-capping cDNA project: toward the understanding of the
RT genesis and biology of neuroblastoma.";
RL Cancer Lett. 197:63-68(2003).
RN [10]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH CTDP1.
RX PubMed=12560496; DOI=10.1093/nar/gkg197;
RA Licciardo P., Amente S., Ruggiero L., Monti M., Pucci P., Lania L.,
RA Majello B.;
RT "The FCP1 phosphatase interacts with RNA polymerase II and with MEP50 a
RT component of the methylosome complex involved in the assembly of snRNP.";
RL Nucleic Acids Res. 31:999-1005(2003).
RN [11]
RP INTERACTION WITH LSM11.
RX PubMed=16087681; DOI=10.1074/jbc.m505077200;
RA Azzouz T.N., Pillai R.S., Dapp C., Chari A., Meister G., Kambach C.,
RA Fischer U., Schuemperli D.;
RT "Toward an assembly line for U7 snRNPs: interactions of U7-specific Lsm
RT proteins with PRMT5 and SMN complexes.";
RL J. Biol. Chem. 280:34435-34440(2005).
RN [12]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH H2AC20; PRMT5 AND 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 [13]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=17437848; DOI=10.1016/j.juro.2007.01.017;
RA Liang J.J., Wang Z., Chiriboga L., Greco M.A., Shapiro E., Huang H.,
RA Yang X.J., Huang J., Peng Y., Melamed J., Garabedian M.J., Lee P.;
RT "The expression and function of androgen receptor coactivator p44 and
RT protein arginine methyltransferase 5 in the developing testis and
RT testicular tumors.";
RL J. Urol. 177:1918-1922(2007).
RN [14]
RP IDENTIFICATION IN THE METHYLOSOME COMPLEX.
RX PubMed=18984161; DOI=10.1016/j.cell.2008.09.020;
RA Chari A., Golas M.M., Klingenhager M., Neuenkirchen N., Sander B.,
RA Englbrecht C., Sickmann A., Stark H., Fischer U.;
RT "An assembly chaperone collaborates with the SMN complex to generate
RT spliceosomal SnRNPs.";
RL Cell 135:497-509(2008).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP INTERACTION WITH APEX1, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19188445; DOI=10.1128/mcb.01337-08;
RA Vascotto C., Fantini D., Romanello M., Cesaratto L., Deganuto M.,
RA Leonardi A., Radicella J.P., Kelley M.R., D'Ambrosio C., Scaloni A.,
RA Quadrifoglio F., Tell G.;
RT "APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the
RT rRNA quality control process.";
RL Mol. Cell. Biol. 29:1834-1854(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-5, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-5, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP SUBUNIT, SUBCELLULAR LOCATION, AND IDENTIFICATION IN A COMPLEX WITH PRTM5;
RP WDR77; RIOK1 OR CLNS1A.
RX PubMed=21081503; DOI=10.1074/jbc.m110.148486;
RA Guderian G., Peter C., Wiesner J., Sickmann A., Schulze-Osthoff K.,
RA Fischer U., Grimmler M.;
RT "RioK1, a new interactor of protein arginine methyltransferase 5 (PRMT5),
RT competes with pICln for binding and modulates PRMT5 complex composition and
RT substrate specificity.";
RL J. Biol. Chem. 286:1976-1986(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-5, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [22]
RP INTERACTION WITH CHTOP, AND IDENTIFICATION IN THE METHYLOSOME COMPLEX WITH
RP PRMT1; PRMT5 AND ERH.
RX PubMed=25284789; DOI=10.1016/j.celrep.2014.08.071;
RA Takai H., Masuda K., Sato T., Sakaguchi Y., Suzuki T., Suzuki T.,
RA Koyama-Nasu R., Nasu-Nishimura Y., Katou Y., Ogawa H., Morishita Y.,
RA Kozuka-Hata H., Oyama M., Todo T., Ino Y., Mukasa A., Saito N.,
RA Toyoshima C., Shirahige K., Akiyama T.;
RT "5-Hydroxymethylcytosine plays a critical role in glioblastomagenesis by
RT recruiting the CHTOP-methylosome complex.";
RL Cell Rep. 9:48-60(2014).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-5, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [24]
RP INTERACTION WITH PRMT5.
RX PubMed=33376131; DOI=10.26508/lsa.202000699;
RA Chakrapani B., Khan M.I.K., Kadumuri R.V., Gupta S., Verma M., Awasthi S.,
RA Govindaraju G., Mahesh A., Rajavelu A., Chavali S., Dhayalan A.;
RT "The uncharacterized protein FAM47E interacts with PRMT5 and regulates its
RT functions.";
RL Life. Sci Alliance 4:e202000699-e202000699(2021).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) OF 2-342 IN COMPLEX WITH PRMT5,
RP FUNCTION, WD REPEATS, AND SUBUNIT.
RX PubMed=23071334; DOI=10.1073/pnas.1209814109;
RA Antonysamy S., Bonday Z., Campbell R.M., Doyle B., Druzina Z., Gheyi T.,
RA Han B., Jungheim L.N., Qian Y., Rauch C., Russell M., Sauder J.M.,
RA Wasserman S.R., Weichert K., Willard F.S., Zhang A., Emtage S.;
RT "Crystal structure of the human PRMT5:MEP50 complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:17960-17965(2012).
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 (PubMed:11756452). This modification targets Sm proteins to the
CC survival of motor neurons (SMN) complex for assembly into small nuclear
CC ribonucleoprotein core particles. Might play a role in transcription
CC regulation. The methylosome complex also methylates the Piwi proteins
CC (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being
CC required for the interaction with Tudor domain-containing proteins and
CC subsequent localization to the meiotic nuage (PubMed:23071334).
CC {ECO:0000269|PubMed:11756452, ECO:0000269|PubMed:23071334}.
CC -!- SUBUNIT: Component of the methylosome complex composed of PRMT5, WDR77
CC and CLNS1A (PubMed:21081503, PubMed:18984161). Found in a complex
CC composed of PRMT5, WDR77 and RIOK1 (PubMed:21081503). RIOK1 and CLNS1A
CC bound directly to PRMT5 at the same binding site, in a mutually
CC exclusive manner, which allows the recruitment of distinct methylation
CC substrates, such as nucleolin/NCL and Sm proteins, respectively
CC (PubMed:21081503). Found in a complex with the component of the
CC methylosome, PRMT5, CLNS1A, WDR77, PRMT1 and ERH (PubMed:25284789).
CC Directly interacts with PRMT5, as well as with several Sm proteins,
CC including SNRPB and SNRPD2 and, more weakly, SNRPD3 and SNRPE
CC (PubMed:11756452, PubMed:33376131). Forms a compact hetero-octamer with
CC PRMT5, decorating the outer surface of a PRMT5 tetramer. Interacts with
CC SUZ12 and histone H2A/H2AC20, but not with histones H2B, H3 nor H4
CC (PubMed:16712789). Interacts with CTDP1 and LSM11 (PubMed:12560496,
CC PubMed:16087681). Interacts with APEX1, AR and NKX3-1 (PubMed:19188445,
CC PubMed:12972618). Interacts with CHTOP (PubMed:25284789). Interacts
CC with FAM47E. {ECO:0000269|PubMed:11756452, ECO:0000269|PubMed:12560496,
CC ECO:0000269|PubMed:12972618, ECO:0000269|PubMed:16087681,
CC ECO:0000269|PubMed:16712789, ECO:0000269|PubMed:18984161,
CC ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:21081503,
CC ECO:0000269|PubMed:23071334, ECO:0000269|PubMed:25284789,
CC ECO:0000269|PubMed:33376131}.
CC -!- INTERACTION:
CC Q9BQA1; P55212: CASP6; NbExp=3; IntAct=EBI-1237307, EBI-718729;
CC Q9BQA1; P04792: HSPB1; NbExp=3; IntAct=EBI-1237307, EBI-352682;
CC Q9BQA1; O60333-2: KIF1B; NbExp=3; IntAct=EBI-1237307, EBI-10975473;
CC Q9BQA1; P13473-2: LAMP2; NbExp=3; IntAct=EBI-1237307, EBI-21591415;
CC Q9BQA1; O14744: PRMT5; NbExp=17; IntAct=EBI-1237307, EBI-351098;
CC Q9BQA1; P62826: RAN; NbExp=3; IntAct=EBI-1237307, EBI-286642;
CC Q9BQA1; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-1237307, EBI-396669;
CC Q9BQA1; O76024: WFS1; NbExp=3; IntAct=EBI-1237307, EBI-720609;
CC Q9BQA1; P03418: N; Xeno; NbExp=3; IntAct=EBI-1237307, EBI-6930799;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17437848,
CC ECO:0000269|PubMed:21081503}. Cytoplasm {ECO:0000269|PubMed:17437848,
CC ECO:0000269|PubMed:21081503}. Note=Nuclear in Leydig cells and
CC cytoplasmic in germ cells during fetal testicular development. In adult
CC testis, predominantly nuclear. Subcellular location varies from nuclear
CC to cytoplasmic in various tumors (PubMed:17437848).
CC {ECO:0000269|PubMed:17437848}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BQA1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BQA1-2; Sequence=VSP_056166;
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, skeletal muscle, spleen,
CC testis, uterus, prostate and thymus. In testis, expressed in germ cells
CC and Leydig cells, but not in peritubular myocytes, nor in Sertoli
CC cells. Expressed in prostate cancers, in seminomas and in Leydig cell
CC tumors. {ECO:0000269|PubMed:12972618, ECO:0000269|PubMed:17437848}.
CC -!- DEVELOPMENTAL STAGE: Expressed in Leydig cells during fetal testicular
CC development, especially during the second semester. Germ cells
CC expression is detected as early as 10 weeks of gestation.
CC {ECO:0000269|PubMed:17437848}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/WDR77ID44142ch1p13.html";
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DR EMBL; AF478464; AAL79917.1; -; mRNA.
DR EMBL; AK022860; BAG51128.1; -; mRNA.
DR EMBL; AK298179; BAG60450.1; -; mRNA.
DR EMBL; AK223189; BAD96909.1; -; mRNA.
DR EMBL; AY225316; AAP79114.1; -; mRNA.
DR EMBL; AB073603; BAD38641.1; -; mRNA.
DR EMBL; AL390195; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471122; EAW56493.1; -; Genomic_DNA.
DR EMBL; BC001679; AAH01679.1; -; mRNA.
DR EMBL; BC006477; AAH06477.1; -; mRNA.
DR EMBL; BC009411; AAH09411.1; -; mRNA.
DR EMBL; BC011778; AAH11778.1; -; mRNA.
DR EMBL; BC016946; AAH16946.1; -; mRNA.
DR EMBL; AB074171; BAE45736.1; -; mRNA.
DR CCDS; CCDS835.1; -. [Q9BQA1-1]
DR RefSeq; NP_001303991.1; NM_001317062.1.
DR RefSeq; NP_001303992.1; NM_001317063.1.
DR RefSeq; NP_001303993.1; NM_001317064.1. [Q9BQA1-2]
DR RefSeq; NP_077007.1; NM_024102.3. [Q9BQA1-1]
DR PDB; 4GQB; X-ray; 2.06 A; B=2-342.
DR PDB; 4X60; X-ray; 2.35 A; B=2-342.
DR PDB; 4X61; X-ray; 2.85 A; B=2-342.
DR PDB; 4X63; X-ray; 3.05 A; B=2-342.
DR PDB; 5C9Z; X-ray; 2.36 A; B=2-342.
DR PDB; 5EMJ; X-ray; 2.27 A; B=2-342.
DR PDB; 5EMK; X-ray; 2.52 A; B=2-342.
DR PDB; 5EML; X-ray; 2.39 A; B=2-342.
DR PDB; 5EMM; X-ray; 2.37 A; B=2-342.
DR PDB; 5FA5; X-ray; 2.34 A; B=2-342.
DR PDB; 6CKC; X-ray; 2.80 A; B=2-342.
DR PDB; 6K1S; X-ray; 2.60 A; B=2-342.
DR PDB; 6RLL; X-ray; 2.22 A; B=2-342.
DR PDB; 6RLQ; X-ray; 2.53 A; B=2-342.
DR PDB; 6UGH; EM; 3.40 A; B=2-342.
DR PDB; 6UXX; X-ray; 2.69 A; B=2-342.
DR PDB; 6UXY; X-ray; 2.57 A; B=2-342.
DR PDB; 6V0N; X-ray; 2.11 A; B=2-342.
DR PDB; 6V0O; X-ray; 2.86 A; B=2-342.
DR PDB; 6V0P; X-ray; 1.88 A; B=2-342.
DR PDB; 7BO7; X-ray; 2.83 A; BBB=2-342.
DR PDB; 7KIB; X-ray; 2.52 A; B=2-342.
DR PDB; 7KIC; X-ray; 2.43 A; B=2-342.
DR PDB; 7KID; X-ray; 2.50 A; B=2-342.
DR PDB; 7L1G; X-ray; 2.47 A; B=2-342.
DR PDB; 7M05; EM; 2.39 A; B/D/F/H=2-342.
DR PDB; 7MX7; X-ray; 2.49 A; B=2-342.
DR PDB; 7MXA; X-ray; 2.71 A; B=2-342.
DR PDB; 7MXC; X-ray; 2.41 A; B=2-342.
DR PDB; 7MXG; X-ray; 2.40 A; B/D=2-342.
DR PDB; 7MXN; X-ray; 2.55 A; B=2-342.
DR PDB; 7S0U; X-ray; 2.01 A; B=2-342.
DR PDB; 7S1P; X-ray; 2.21 A; B=2-342.
DR PDB; 7S1Q; X-ray; 2.78 A; B=2-342.
DR PDB; 7S1R; X-ray; 2.10 A; B=2-342.
DR PDB; 7S1S; X-ray; 2.62 A; B=2-342.
DR PDB; 7SER; X-ray; 2.14 A; B=2-342.
DR PDB; 7SES; X-ray; 2.50 A; B=2-342.
DR PDBsum; 4GQB; -.
DR PDBsum; 4X60; -.
DR PDBsum; 4X61; -.
DR PDBsum; 4X63; -.
DR PDBsum; 5C9Z; -.
DR PDBsum; 5EMJ; -.
DR PDBsum; 5EMK; -.
DR PDBsum; 5EML; -.
DR PDBsum; 5EMM; -.
DR PDBsum; 5FA5; -.
DR PDBsum; 6CKC; -.
DR PDBsum; 6K1S; -.
DR PDBsum; 6RLL; -.
DR PDBsum; 6RLQ; -.
DR PDBsum; 6UGH; -.
DR PDBsum; 6UXX; -.
DR PDBsum; 6UXY; -.
DR PDBsum; 6V0N; -.
DR PDBsum; 6V0O; -.
DR PDBsum; 6V0P; -.
DR PDBsum; 7BO7; -.
DR PDBsum; 7KIB; -.
DR PDBsum; 7KIC; -.
DR PDBsum; 7KID; -.
DR PDBsum; 7L1G; -.
DR PDBsum; 7M05; -.
DR PDBsum; 7MX7; -.
DR PDBsum; 7MXA; -.
DR PDBsum; 7MXC; -.
DR PDBsum; 7MXG; -.
DR PDBsum; 7MXN; -.
DR PDBsum; 7S0U; -.
DR PDBsum; 7S1P; -.
DR PDBsum; 7S1Q; -.
DR PDBsum; 7S1R; -.
DR PDBsum; 7S1S; -.
DR PDBsum; 7SER; -.
DR PDBsum; 7SES; -.
DR AlphaFoldDB; Q9BQA1; -.
DR SMR; Q9BQA1; -.
DR BioGRID; 122532; 329.
DR ComplexPortal; CPX-696; PRMT5 methylosome complex.
DR CORUM; Q9BQA1; -.
DR DIP; DIP-38172N; -.
DR IntAct; Q9BQA1; 100.
DR MINT; Q9BQA1; -.
DR STRING; 9606.ENSP00000235090; -.
DR BindingDB; Q9BQA1; -.
DR ChEMBL; CHEMBL3108649; -.
DR GlyGen; Q9BQA1; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BQA1; -.
DR PhosphoSitePlus; Q9BQA1; -.
DR SwissPalm; Q9BQA1; -.
DR BioMuta; WDR77; -.
DR DMDM; 32171507; -.
DR REPRODUCTION-2DPAGE; IPI00012202; -.
DR EPD; Q9BQA1; -.
DR jPOST; Q9BQA1; -.
DR MassIVE; Q9BQA1; -.
DR MaxQB; Q9BQA1; -.
DR PaxDb; Q9BQA1; -.
DR PeptideAtlas; Q9BQA1; -.
DR PRIDE; Q9BQA1; -.
DR ProteomicsDB; 4753; -.
DR ProteomicsDB; 78647; -. [Q9BQA1-1]
DR Antibodypedia; 35257; 291 antibodies from 33 providers.
DR DNASU; 79084; -.
DR Ensembl; ENST00000235090.10; ENSP00000235090.5; ENSG00000116455.14. [Q9BQA1-1]
DR GeneID; 79084; -.
DR KEGG; hsa:79084; -.
DR MANE-Select; ENST00000235090.10; ENSP00000235090.5; NM_024102.4; NP_077007.1.
DR UCSC; uc001ebb.4; human. [Q9BQA1-1]
DR CTD; 79084; -.
DR DisGeNET; 79084; -.
DR GeneCards; WDR77; -.
DR HGNC; HGNC:29652; WDR77.
DR HPA; ENSG00000116455; Tissue enhanced (fallopian).
DR MIM; 611734; gene.
DR neXtProt; NX_Q9BQA1; -.
DR OpenTargets; ENSG00000116455; -.
DR PharmGKB; PA142670581; -.
DR VEuPathDB; HostDB:ENSG00000116455; -.
DR eggNOG; KOG0284; Eukaryota.
DR GeneTree; ENSGT00390000010711; -.
DR HOGENOM; CLU_051285_0_0_1; -.
DR InParanoid; Q9BQA1; -.
DR OMA; CVTRLVF; -.
DR OrthoDB; 774546at2759; -.
DR PhylomeDB; Q9BQA1; -.
DR TreeFam; TF325967; -.
DR PathwayCommons; Q9BQA1; -.
DR Reactome; R-HSA-191859; snRNP Assembly.
DR Reactome; R-HSA-3214858; RMTs methylate histone arginines.
DR SignaLink; Q9BQA1; -.
DR BioGRID-ORCS; 79084; 731 hits in 1090 CRISPR screens.
DR ChiTaRS; WDR77; human.
DR GeneWiki; WD_repeat-containing_protein_77; -.
DR GenomeRNAi; 79084; -.
DR Pharos; Q9BQA1; Tbio.
DR PRO; PR:Q9BQA1; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9BQA1; protein.
DR Bgee; ENSG00000116455; Expressed in right uterine tube and 200 other tissues.
DR ExpressionAtlas; Q9BQA1; baseline and differential.
DR Genevisible; Q9BQA1; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0034709; C:methylosome; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008327; F:methyl-CpG binding; IDA:UniProtKB.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; IGI:MGI.
DR GO; GO:0060767; P:epithelial cell proliferation involved in prostate gland development; IEA:Ensembl.
DR GO; GO:0043985; P:histone H4-R3 methylation; IC:ComplexPortal.
DR GO; GO:0060770; P:negative regulation of epithelial cell proliferation involved in prostate gland development; IEA:Ensembl.
DR GO; GO:0007309; P:oocyte axis specification; IBA:GO_Central.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0060528; P:secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development; IEA:Ensembl.
DR GO; GO:0000387; P:spliceosomal snRNP assembly; IC:ComplexPortal.
DR Gene3D; 2.130.10.10; -; 1.
DR IDEAL; IID00583; -.
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; 1.
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 3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; WD repeat.
FT CHAIN 1..342
FT /note="Methylosome protein 50"
FT /id="PRO_0000051074"
FT REPEAT 22..75
FT /note="WD 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221,
FT ECO:0000269|PubMed:23071334"
FT REPEAT 78..116
FT /note="WD 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221,
FT ECO:0000269|PubMed:23071334"
FT REPEAT 123..162
FT /note="WD 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221,
FT ECO:0000269|PubMed:23071334"
FT REPEAT 165..205
FT /note="WD 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221,
FT ECO:0000269|PubMed:23071334"
FT REPEAT 209..250
FT /note="WD 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221,
FT ECO:0000269|PubMed:23071334"
FT REPEAT 253..293
FT /note="WD 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221,
FT ECO:0000269|PubMed:23071334"
FT REPEAT 295..330
FT /note="WD 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221,
FT ECO:0000269|PubMed:23071334"
FT MOD_RES 5
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 101..164
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056166"
FT VARIANT 48
FT /note="S -> I (in dbSNP:rs7416672)"
FT /id="VAR_042903"
FT CONFLICT 244
FT /note="S -> N (in Ref. 2; BAD96909)"
FT /evidence="ECO:0000305"
FT CONFLICT 313..342
FT /note="LTTVGWDHQVVHHVVPTEPLPAPGPASVTE -> DLQVLLSRLDLRQKASPP
FT (in Ref. 7; AAH09411)"
FT /evidence="ECO:0000305"
FT STRAND 29..36
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:7MXC"
FT STRAND 42..47
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 56..63
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 64..66
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 74..81
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 83..89
FT /evidence="ECO:0007829|PDB:6V0P"
FT TURN 90..92
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 93..98
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 101..108
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 110..112
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 115..122
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:6RLL"
FT STRAND 128..133
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 137..144
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:6UGH"
FT STRAND 149..153
FT /evidence="ECO:0007829|PDB:6V0P"
FT TURN 154..157
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 158..163
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 170..175
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 182..187
FT /evidence="ECO:0007829|PDB:6V0P"
FT TURN 188..190
FT /evidence="ECO:0007829|PDB:6UXX"
FT STRAND 192..196
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 199..201
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:6V0O"
FT STRAND 215..220
FT /evidence="ECO:0007829|PDB:6V0P"
FT TURN 222..224
FT /evidence="ECO:0007829|PDB:7S0U"
FT STRAND 227..232
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 235..242
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:7MXN"
FT STRAND 249..252
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 258..263
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 265..268
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 271..275
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 280..283
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 289..293
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 300..305
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 307..309
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 312..317
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 322..326
FT /evidence="ECO:0007829|PDB:6V0P"
SQ SEQUENCE 342 AA; 36724 MW; 3D355AEC68491ECB CRC64;
MRKETPPPLV PPAAREWNLP PNAPACMERQ LEAARYRSDG ALLLGASSLS GRCWAGSLWL
FKDPCAAPNE GFCSAGVQTE AGVADLTWVG ERGILVASDS GAVELWELDE NETLIVSKFC
KYEHDDIVST VSVLSSGTQA VSGSKDICIK VWDLAQQVVL SSYRAHAAQV TCVAASPHKD
SVFLSCSEDN RILLWDTRCP KPASQIGCSA PGYLPTSLAW HPQQSEVFVF GDENGTVSLV
DTKSTSCVLS SAVHSQCVTG LVFSPHSVPF LASLSEDCSL AVLDSSLSEL FRSQAHRDFV
RDATWSPLNH SLLTTVGWDH QVVHHVVPTE PLPAPGPASV TE
