Full text data of WDR77
WDR77
(MEP50)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Methylosome protein 50; MEP-50 (Androgen receptor cofactor p44; WD repeat-containing protein 77; p44/Mep50)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Methylosome protein 50; MEP-50 (Androgen receptor cofactor p44; WD repeat-containing protein 77; p44/Mep50)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9BQA1
ID MEP50_HUMAN Reviewed; 342 AA.
AC Q9BQA1; B3KMW6; Q3LID2; Q53FU2; Q6JZZ5; Q96GK4; Q9BWY3;
DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-2001, sequence version 1.
DT 22-JAN-2014, entry version 113.
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; ORFNames=HKMT1069, Nbla10071;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 4-15; 38-52; 122-145;
RP 151-164 AND 192-198, FUNCTION, INTERACTION WITH PRMT5; SNRPB; SNRPD2;
RP SNRPD3 AND SNRPE, AND 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], 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
RT in androgen receptor-dependent transcription.";
RL Mol. Cell. Biol. 23:7019-7029(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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].
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.,
RA Sugano S., Hirata T., Goto T., Matsunaga T., Hiyama E., Hayashi Y.,
RA Ando H., Suita S., Kaneko M., Sasaki F., Hashizume K., Ohnuma N.,
RA Nakagawara A.;
RT "Expression profiling and differential screening between
RT hepatoblastomas and the corresponding normal livers: identification of
RT high expression of the PLK1 oncogene as a poor-prognostic indicator of
RT 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.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA 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.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA 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.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: 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 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.
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
RT the 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
RT a component of the methylosome complex involved in the assembly of
RT 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
RT Lsm proteins with PRMT5 and SMN complexes.";
RL J. Biol. Chem. 280:34435-34440(2005).
RN [12]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH HIST2H2AC; 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 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 [15]
RP INTERACTION WITH APEX1, MASS SPECTROMETRY, AND 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
RT the rRNA quality control process.";
RL Mol. Cell. Biol. 29:1834-1854(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-5, AND MASS
RP SPECTROMETRY.
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-5, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
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.,
RA Buerckstuemmer T., 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 [19]
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.,
RA Gheyi T., Han B., Jungheim L.N., Qian Y., Rauch C., Russell M.,
RA Sauder J.M., Wasserman S.R., Weichert K., Willard F.S., Zhang A.,
RA 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 20S PRMT5-containing
CC methyltransferase complex, which modifies specific arginines to
CC dimethylarginines in several spliceosomal Sm proteins and
CC histones. This modification targets Sm proteins to the survival of
CC motor neurons (SMN) complex for assembly into small nuclear
CC ribonucleoprotein core particles. Might play a role in
CC transcription regulation. The 20S PRMT5-containing
CC methyltransferase 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
CC and subsequent localization to the meiotic nuage.
CC -!- SUBUNIT: Component of the methylosome, a 20S complex containing at
CC least PRMT5, CLNS1A and WDR77. Directly interacts with PRMT5, as
CC well as with several Sm proteins, including SNRPB and SNRPD2 and,
CC more weakly, SNRPD3 and SNRPE. Forms a compact hetero-octamer with
CC PRMT5, decorating the outer surface of a PRMT5 tetramer. Interacts
CC with SUZ12 and histone H2A/HIST2H2AC, but not with histones H2B,
CC H3 nor H4. Interacts with CTDP1 and LSM11. Interacts with APEX1,
CC AR and NKX3-1.
CC -!- INTERACTION:
CC O14744:PRMT5; NbExp=6; IntAct=EBI-1237307, EBI-351098;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Nuclear in Leydig
CC cells and cytoplasmic in germ cells during fetal testicular
CC development. In adult testis, predominantly nuclear. Subcellular
CC location varies from nuclear to cytoplasmic in various tumors.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, skeletal muscle,
CC spleen, testis, uterus, prostate and thymus. In testis, expressed
CC in germ cells and Leydig cells, but not in peritubular myocytes,
CC nor in Sertoli cells. Expressed in prostate cancers, in seminomas
CC and in Leydig cell tumors.
CC -!- DEVELOPMENTAL STAGE: Expressed in Leydig cells during fetal
CC testicular development, especially during the second semester.
CC Germ cells expression is detected as early as 10 weeks of
CC gestation.
CC -!- SIMILARITY: Contains 7 WD repeats.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and 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; AK223189; BAD96909.1; -; mRNA.
DR EMBL; AY225316; AAP79114.1; -; mRNA.
DR EMBL; AB073603; BAD38641.1; -; mRNA.
DR EMBL; AL390195; CAC36041.1; -; 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 RefSeq; NP_077007.1; NM_024102.2.
DR UniGene; Hs.204773; -.
DR PDB; 4GQB; X-ray; 2.06 A; B=2-342.
DR PDBsum; 4GQB; -.
DR ProteinModelPortal; Q9BQA1; -.
DR SMR; Q9BQA1; 21-329.
DR DIP; DIP-38172N; -.
DR IntAct; Q9BQA1; 42.
DR MINT; MINT-1217135; -.
DR STRING; 9606.ENSP00000235090; -.
DR PhosphoSite; Q9BQA1; -.
DR DMDM; 32171507; -.
DR REPRODUCTION-2DPAGE; IPI00012202; -.
DR PaxDb; Q9BQA1; -.
DR PeptideAtlas; Q9BQA1; -.
DR PRIDE; Q9BQA1; -.
DR DNASU; 79084; -.
DR Ensembl; ENST00000235090; ENSP00000235090; ENSG00000116455.
DR GeneID; 79084; -.
DR KEGG; hsa:79084; -.
DR UCSC; uc001ebb.3; human.
DR CTD; 79084; -.
DR GeneCards; GC01M111983; -.
DR HGNC; HGNC:29652; WDR77.
DR HPA; HPA026437; -.
DR HPA; HPA026448; -.
DR HPA; HPA027271; -.
DR MIM; 611734; gene.
DR neXtProt; NX_Q9BQA1; -.
DR PharmGKB; PA142670581; -.
DR eggNOG; COG2319; -.
DR HOVERGEN; HBG052458; -.
DR InParanoid; Q9BQA1; -.
DR KO; K13221; -.
DR OMA; MRKETPP; -.
DR OrthoDB; EOG7KSX99; -.
DR PhylomeDB; Q9BQA1; -.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR SignaLink; Q9BQA1; -.
DR GeneWiki; WD_repeat-containing_protein_77; -.
DR GenomeRNAi; 79084; -.
DR NextBio; 67897; -.
DR PRO; PR:Q9BQA1; -.
DR ArrayExpress; Q9BQA1; -.
DR Bgee; Q9BQA1; -.
DR CleanEx; HS_WDR77; -.
DR Genevestigator; Q9BQA1; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0030374; F:ligand-dependent nuclear receptor transcription coactivator activity; IGI:MGI.
DR GO; GO:0034660; P:ncRNA metabolic process; TAS:Reactome.
DR GO; GO:0060770; P:negative regulation of epithelial cell proliferation involved in prostate gland development; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; 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; TAS:Reactome.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR017986; WD40_repeat_dom.
DR Pfam; PF00400; WD40; 3.
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; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW WD repeat.
FT CHAIN 1 342 Methylosome protein 50.
FT /FTId=PRO_0000051074.
FT REPEAT 22 75 WD 1.
FT REPEAT 78 116 WD 2.
FT REPEAT 123 162 WD 3.
FT REPEAT 165 205 WD 4.
FT REPEAT 209 250 WD 5.
FT REPEAT 253 293 WD 6.
FT REPEAT 295 330 WD 7.
FT MOD_RES 5 5 Phosphothreonine.
FT VARIANT 48 48 S -> I (in dbSNP:rs7416672).
FT /FTId=VAR_042903.
FT CONFLICT 244 244 S -> N (in Ref. 2; BAD96909).
FT CONFLICT 313 342 LTTVGWDHQVVHHVVPTEPLPAPGPASVTE -> DLQVLLS
FT RLDLRQKASPP (in Ref. 7; AAH09411).
FT STRAND 29 36
FT STRAND 42 47
FT STRAND 50 52
FT STRAND 56 63
FT HELIX 64 66
FT HELIX 70 72
FT STRAND 74 81
FT STRAND 83 89
FT TURN 90 92
FT STRAND 93 98
FT STRAND 101 108
FT STRAND 115 122
FT STRAND 128 133
FT STRAND 137 144
FT STRAND 149 153
FT TURN 154 157
FT STRAND 158 163
FT STRAND 170 175
FT STRAND 182 187
FT STRAND 192 196
FT STRAND 199 201
FT STRAND 203 205
FT STRAND 215 220
FT STRAND 227 232
FT STRAND 235 242
FT STRAND 249 252
FT STRAND 258 263
FT STRAND 265 268
FT STRAND 271 275
FT STRAND 280 283
FT STRAND 289 293
FT STRAND 300 305
FT STRAND 307 309
FT STRAND 312 317
FT STRAND 322 326
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
//
ID MEP50_HUMAN Reviewed; 342 AA.
AC Q9BQA1; B3KMW6; Q3LID2; Q53FU2; Q6JZZ5; Q96GK4; Q9BWY3;
DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-2001, sequence version 1.
DT 22-JAN-2014, entry version 113.
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; ORFNames=HKMT1069, Nbla10071;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 4-15; 38-52; 122-145;
RP 151-164 AND 192-198, FUNCTION, INTERACTION WITH PRMT5; SNRPB; SNRPD2;
RP SNRPD3 AND SNRPE, AND 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], 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
RT in androgen receptor-dependent transcription.";
RL Mol. Cell. Biol. 23:7019-7029(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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].
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.,
RA Sugano S., Hirata T., Goto T., Matsunaga T., Hiyama E., Hayashi Y.,
RA Ando H., Suita S., Kaneko M., Sasaki F., Hashizume K., Ohnuma N.,
RA Nakagawara A.;
RT "Expression profiling and differential screening between
RT hepatoblastomas and the corresponding normal livers: identification of
RT high expression of the PLK1 oncogene as a poor-prognostic indicator of
RT 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.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA 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.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA 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.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: 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 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.
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
RT the 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
RT a component of the methylosome complex involved in the assembly of
RT 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
RT Lsm proteins with PRMT5 and SMN complexes.";
RL J. Biol. Chem. 280:34435-34440(2005).
RN [12]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH HIST2H2AC; 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 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 [15]
RP INTERACTION WITH APEX1, MASS SPECTROMETRY, AND 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
RT the rRNA quality control process.";
RL Mol. Cell. Biol. 29:1834-1854(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-5, AND MASS
RP SPECTROMETRY.
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-5, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
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.,
RA Buerckstuemmer T., 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 [19]
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.,
RA Gheyi T., Han B., Jungheim L.N., Qian Y., Rauch C., Russell M.,
RA Sauder J.M., Wasserman S.R., Weichert K., Willard F.S., Zhang A.,
RA 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 20S PRMT5-containing
CC methyltransferase complex, which modifies specific arginines to
CC dimethylarginines in several spliceosomal Sm proteins and
CC histones. This modification targets Sm proteins to the survival of
CC motor neurons (SMN) complex for assembly into small nuclear
CC ribonucleoprotein core particles. Might play a role in
CC transcription regulation. The 20S PRMT5-containing
CC methyltransferase 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
CC and subsequent localization to the meiotic nuage.
CC -!- SUBUNIT: Component of the methylosome, a 20S complex containing at
CC least PRMT5, CLNS1A and WDR77. Directly interacts with PRMT5, as
CC well as with several Sm proteins, including SNRPB and SNRPD2 and,
CC more weakly, SNRPD3 and SNRPE. Forms a compact hetero-octamer with
CC PRMT5, decorating the outer surface of a PRMT5 tetramer. Interacts
CC with SUZ12 and histone H2A/HIST2H2AC, but not with histones H2B,
CC H3 nor H4. Interacts with CTDP1 and LSM11. Interacts with APEX1,
CC AR and NKX3-1.
CC -!- INTERACTION:
CC O14744:PRMT5; NbExp=6; IntAct=EBI-1237307, EBI-351098;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Nuclear in Leydig
CC cells and cytoplasmic in germ cells during fetal testicular
CC development. In adult testis, predominantly nuclear. Subcellular
CC location varies from nuclear to cytoplasmic in various tumors.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, skeletal muscle,
CC spleen, testis, uterus, prostate and thymus. In testis, expressed
CC in germ cells and Leydig cells, but not in peritubular myocytes,
CC nor in Sertoli cells. Expressed in prostate cancers, in seminomas
CC and in Leydig cell tumors.
CC -!- DEVELOPMENTAL STAGE: Expressed in Leydig cells during fetal
CC testicular development, especially during the second semester.
CC Germ cells expression is detected as early as 10 weeks of
CC gestation.
CC -!- SIMILARITY: Contains 7 WD repeats.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and 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; AK223189; BAD96909.1; -; mRNA.
DR EMBL; AY225316; AAP79114.1; -; mRNA.
DR EMBL; AB073603; BAD38641.1; -; mRNA.
DR EMBL; AL390195; CAC36041.1; -; 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 RefSeq; NP_077007.1; NM_024102.2.
DR UniGene; Hs.204773; -.
DR PDB; 4GQB; X-ray; 2.06 A; B=2-342.
DR PDBsum; 4GQB; -.
DR ProteinModelPortal; Q9BQA1; -.
DR SMR; Q9BQA1; 21-329.
DR DIP; DIP-38172N; -.
DR IntAct; Q9BQA1; 42.
DR MINT; MINT-1217135; -.
DR STRING; 9606.ENSP00000235090; -.
DR PhosphoSite; Q9BQA1; -.
DR DMDM; 32171507; -.
DR REPRODUCTION-2DPAGE; IPI00012202; -.
DR PaxDb; Q9BQA1; -.
DR PeptideAtlas; Q9BQA1; -.
DR PRIDE; Q9BQA1; -.
DR DNASU; 79084; -.
DR Ensembl; ENST00000235090; ENSP00000235090; ENSG00000116455.
DR GeneID; 79084; -.
DR KEGG; hsa:79084; -.
DR UCSC; uc001ebb.3; human.
DR CTD; 79084; -.
DR GeneCards; GC01M111983; -.
DR HGNC; HGNC:29652; WDR77.
DR HPA; HPA026437; -.
DR HPA; HPA026448; -.
DR HPA; HPA027271; -.
DR MIM; 611734; gene.
DR neXtProt; NX_Q9BQA1; -.
DR PharmGKB; PA142670581; -.
DR eggNOG; COG2319; -.
DR HOVERGEN; HBG052458; -.
DR InParanoid; Q9BQA1; -.
DR KO; K13221; -.
DR OMA; MRKETPP; -.
DR OrthoDB; EOG7KSX99; -.
DR PhylomeDB; Q9BQA1; -.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR SignaLink; Q9BQA1; -.
DR GeneWiki; WD_repeat-containing_protein_77; -.
DR GenomeRNAi; 79084; -.
DR NextBio; 67897; -.
DR PRO; PR:Q9BQA1; -.
DR ArrayExpress; Q9BQA1; -.
DR Bgee; Q9BQA1; -.
DR CleanEx; HS_WDR77; -.
DR Genevestigator; Q9BQA1; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0030374; F:ligand-dependent nuclear receptor transcription coactivator activity; IGI:MGI.
DR GO; GO:0034660; P:ncRNA metabolic process; TAS:Reactome.
DR GO; GO:0060770; P:negative regulation of epithelial cell proliferation involved in prostate gland development; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; 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; TAS:Reactome.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR017986; WD40_repeat_dom.
DR Pfam; PF00400; WD40; 3.
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; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW WD repeat.
FT CHAIN 1 342 Methylosome protein 50.
FT /FTId=PRO_0000051074.
FT REPEAT 22 75 WD 1.
FT REPEAT 78 116 WD 2.
FT REPEAT 123 162 WD 3.
FT REPEAT 165 205 WD 4.
FT REPEAT 209 250 WD 5.
FT REPEAT 253 293 WD 6.
FT REPEAT 295 330 WD 7.
FT MOD_RES 5 5 Phosphothreonine.
FT VARIANT 48 48 S -> I (in dbSNP:rs7416672).
FT /FTId=VAR_042903.
FT CONFLICT 244 244 S -> N (in Ref. 2; BAD96909).
FT CONFLICT 313 342 LTTVGWDHQVVHHVVPTEPLPAPGPASVTE -> DLQVLLS
FT RLDLRQKASPP (in Ref. 7; AAH09411).
FT STRAND 29 36
FT STRAND 42 47
FT STRAND 50 52
FT STRAND 56 63
FT HELIX 64 66
FT HELIX 70 72
FT STRAND 74 81
FT STRAND 83 89
FT TURN 90 92
FT STRAND 93 98
FT STRAND 101 108
FT STRAND 115 122
FT STRAND 128 133
FT STRAND 137 144
FT STRAND 149 153
FT TURN 154 157
FT STRAND 158 163
FT STRAND 170 175
FT STRAND 182 187
FT STRAND 192 196
FT STRAND 199 201
FT STRAND 203 205
FT STRAND 215 220
FT STRAND 227 232
FT STRAND 235 242
FT STRAND 249 252
FT STRAND 258 263
FT STRAND 265 268
FT STRAND 271 275
FT STRAND 280 283
FT STRAND 289 293
FT STRAND 300 305
FT STRAND 307 309
FT STRAND 312 317
FT STRAND 322 326
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
//
MIM
611734
*RECORD*
*FIELD* NO
611734
*FIELD* TI
*611734 WD REPEAT-CONTAINING PROTEIN 77; WDR77
;;METHYLOSOME PROTEIN, 50-KD; MEP50;;
read moreANDROGEN RECEPTOR-ASSOCIATED PROTEIN, 44-KD; p44
*FIELD* TX
DESCRIPTION
WDR77 is a component of the 20S PRMT5 (604045)-containing
methyltransferase complex, which modifies specific arginines to
dimethylarginines in several spliceosomal Sm proteins (see 601061). This
modification targets Sm proteins to the survival of motor neurons (SMN)
complex (see 600354) for assembly into small nuclear ribonucleoprotein
core particles (Friesen et al., 2002).
CLONING
By peptide sequencing of a protein associated with the 20S
methyltransferase complex, followed by database analysis, Friesen et al.
(2002) obtained a full-length clone encoding WDR77, which they called
MEP50. The deduced 342-amino acid protein has 6 WD repeats and has a
calculated molecular mass of 36.7 kD. By SDS-PAGE, MEP50 had an apparent
molecular mass of 50 kD.
Using biochemical cellular fractionation and immunofluorescence
analysis, Licciardo et al. (2003) showed that MEP50 localized to both
the nucleus and cytoplasm in human cells.
Liang et al. (2007) showed that PRMT5 and WDR77, which they called p44,
were expressed predominantly as nuclear proteins in fetal Leydig cells
and adult human testis, whereas they were predominantly cytoplasmic in
fetal germ cells.
GENE FUNCTION
Friesen et al. (2002) showed that endogenous MEP50 associated with PRMT5
in the 20S arginine methyltransferase complex in HeLa cells. Protein
pull-down assays revealed that MEP50 specifically interacted with SmB
(SNRPB; 182282) and SmD2 (SNRPD2; 601061) and more weakly with SmD3
(SNRPD3; 601062) and SmE (SNRPE; 128260). Antibodies directed against
MEP50 significantly reduced the arginine methyltransferase activity of
the immunopurified complex toward Sm substrates.
FCP1 (CTDP1; 604927) is a phosphatase specific for the C-terminal domain
(CTD) of the large subunit of RNA polymerase II (POLR2A; 180660), which
is cyclically phosphorylated during RNA polymerase II transcription.
Licciardo et al. (2003) found that FCP1-affinity purified complexes in
an FCP1-expressing human lung carcinoma cell line (H1299) contained
MEP50 and RNA polymerase II. Glycerol gradient fractionation and Western
blot analysis of H1299 whole cell extracts detected MEP50 in protein
complexes of 400 kD and more than 800 kD. In nuclear extracts, MEP50 was
associated only with the 400-kD complex, which also appeared to contain
FCP1 and was distinct from the larger methyltransferase complex
containing PRMT5.
SUZ12 (606245) belongs to the polycomb group of proteins, which mediate
chromatin modification and epigenetic repression of gene expression.
Using yeast 2-hybrid, coimmunoprecipitation, and protein pull-down
analyses, Furuno et al. (2006) found that SUZ12 interacted with mouse
and human MEP50. Human MEP50 interacted with free histone H2a (see
601772) from calf thymus, but not with other histones or with H2A
complexed in isolated HeLa cell nucleosomes. PRMT5-mediated
transcriptional repression of a reporter gene was dependent on MEP50.
Furuno et al. (2006) concluded that MEP50 may be an adaptor between
PRMT5 and its H2A substrate and that SUZ12 may have a role in
transcriptional regulation through physical interaction with MEP50.
Using in vitro assays and in vivo tumor xenograft experiments, Peng et
al. (2008) showed that nuclear human p44 inhibits prostate cancer (see
176807) growth, at least in part, through the regulation of cell cycle
regulatory genes that include p21 (CDKN1A; 116899). Conversely,
cytoplasmic p44 promoted prostate cancer growth through upregulation of
cyclin D2 (123833) and CDK6 (603368). Immunofluorescence analysis of
prostate cancer tissue indicated that nuclear exclusion of p44 was
associated with androgen-independent prostate cancer.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the WDR77
gene to chromosome 1 (TMAP RH11857).
ANIMAL MODEL
Liang et al. (2007) showed that heterozygous Wdr77 knockout mice had
increased testicular size and increased numbers of spermatocytes,
spermatozoa, and spermatids compared with testis from wildtype mice.
*FIELD* RF
1. Friesen, W. J.; Wyce, A.; Paushkin, S.; Abel, L.; Rappsilbers,
J.; Mann, M.; Dreyfuss, G.: A novel WD repeat protein component of
the methylosome binds Sm proteins. J. Biol. Chem. 277: 8243-8247,
2002.
2. Furuno, K.; Masatsugu, T.; Sonoda, M.; Sasazuki, T.; Yamamoto,
K.: Association of Polycomb group SUZ12 with WD-repeat protein MEP50
that binds to histone H2A selectively in vitro. Biochem. Biophys.
Res. Commun. 345: 1051-1058, 2006.
3. Liang, J. J.; Wang, Z.; Chiriboga, L.; Greco, M. A.; Shapiro, E.;
Huang, H.; Yang, X. J.; Huang, J.; Peng, Y.; Malamed, J.; Garabedian,
M. J.; Lee, P.: The expression and function of androgen receptor
coactivator p44 and protein arginine methyltransferase 5 in the developing
testis and testicular tumors. J. Urology 177: 1918-1922, 2007.
4. Licciardo, P.; Amente, S.; Ruggiero, L.; Monti, M.; Pucci, P.;
Lania, L.; Majello, B.: The FCP1 phosphatase interacts with RNA polymerase
II and with MEP50 a component of the methylosome complex involved
in the assembly of snRNP. Nucleic Acids Res. 31: 999-1005, 2003.
5. Peng, Y.; Chen, F.; Melamed, J.; Chiriboga, L.; Wei, J.; Kong,
X.; Mcleod, M.; Li, Y.; Li, C. X.; Feng, A.; Garabedian, M. J.; Wang,
Z.; Roeder, R. G.; Lee, P.: Distinct nuclear and cytoplasmic functions
of androgen receptor cofactor p44 and association with androgen-independent
prostate cancer. Proc. Nat. Acad. Sci. 105: 5236-5241, 2008.
*FIELD* CN
Patricia A. Hartz - updated: 6/5/2008
*FIELD* CD
Patricia A. Hartz: 1/17/2008
*FIELD* ED
alopez: 06/26/2008
terry: 6/5/2008
mgross: 1/17/2008
*RECORD*
*FIELD* NO
611734
*FIELD* TI
*611734 WD REPEAT-CONTAINING PROTEIN 77; WDR77
;;METHYLOSOME PROTEIN, 50-KD; MEP50;;
read moreANDROGEN RECEPTOR-ASSOCIATED PROTEIN, 44-KD; p44
*FIELD* TX
DESCRIPTION
WDR77 is a component of the 20S PRMT5 (604045)-containing
methyltransferase complex, which modifies specific arginines to
dimethylarginines in several spliceosomal Sm proteins (see 601061). This
modification targets Sm proteins to the survival of motor neurons (SMN)
complex (see 600354) for assembly into small nuclear ribonucleoprotein
core particles (Friesen et al., 2002).
CLONING
By peptide sequencing of a protein associated with the 20S
methyltransferase complex, followed by database analysis, Friesen et al.
(2002) obtained a full-length clone encoding WDR77, which they called
MEP50. The deduced 342-amino acid protein has 6 WD repeats and has a
calculated molecular mass of 36.7 kD. By SDS-PAGE, MEP50 had an apparent
molecular mass of 50 kD.
Using biochemical cellular fractionation and immunofluorescence
analysis, Licciardo et al. (2003) showed that MEP50 localized to both
the nucleus and cytoplasm in human cells.
Liang et al. (2007) showed that PRMT5 and WDR77, which they called p44,
were expressed predominantly as nuclear proteins in fetal Leydig cells
and adult human testis, whereas they were predominantly cytoplasmic in
fetal germ cells.
GENE FUNCTION
Friesen et al. (2002) showed that endogenous MEP50 associated with PRMT5
in the 20S arginine methyltransferase complex in HeLa cells. Protein
pull-down assays revealed that MEP50 specifically interacted with SmB
(SNRPB; 182282) and SmD2 (SNRPD2; 601061) and more weakly with SmD3
(SNRPD3; 601062) and SmE (SNRPE; 128260). Antibodies directed against
MEP50 significantly reduced the arginine methyltransferase activity of
the immunopurified complex toward Sm substrates.
FCP1 (CTDP1; 604927) is a phosphatase specific for the C-terminal domain
(CTD) of the large subunit of RNA polymerase II (POLR2A; 180660), which
is cyclically phosphorylated during RNA polymerase II transcription.
Licciardo et al. (2003) found that FCP1-affinity purified complexes in
an FCP1-expressing human lung carcinoma cell line (H1299) contained
MEP50 and RNA polymerase II. Glycerol gradient fractionation and Western
blot analysis of H1299 whole cell extracts detected MEP50 in protein
complexes of 400 kD and more than 800 kD. In nuclear extracts, MEP50 was
associated only with the 400-kD complex, which also appeared to contain
FCP1 and was distinct from the larger methyltransferase complex
containing PRMT5.
SUZ12 (606245) belongs to the polycomb group of proteins, which mediate
chromatin modification and epigenetic repression of gene expression.
Using yeast 2-hybrid, coimmunoprecipitation, and protein pull-down
analyses, Furuno et al. (2006) found that SUZ12 interacted with mouse
and human MEP50. Human MEP50 interacted with free histone H2a (see
601772) from calf thymus, but not with other histones or with H2A
complexed in isolated HeLa cell nucleosomes. PRMT5-mediated
transcriptional repression of a reporter gene was dependent on MEP50.
Furuno et al. (2006) concluded that MEP50 may be an adaptor between
PRMT5 and its H2A substrate and that SUZ12 may have a role in
transcriptional regulation through physical interaction with MEP50.
Using in vitro assays and in vivo tumor xenograft experiments, Peng et
al. (2008) showed that nuclear human p44 inhibits prostate cancer (see
176807) growth, at least in part, through the regulation of cell cycle
regulatory genes that include p21 (CDKN1A; 116899). Conversely,
cytoplasmic p44 promoted prostate cancer growth through upregulation of
cyclin D2 (123833) and CDK6 (603368). Immunofluorescence analysis of
prostate cancer tissue indicated that nuclear exclusion of p44 was
associated with androgen-independent prostate cancer.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the WDR77
gene to chromosome 1 (TMAP RH11857).
ANIMAL MODEL
Liang et al. (2007) showed that heterozygous Wdr77 knockout mice had
increased testicular size and increased numbers of spermatocytes,
spermatozoa, and spermatids compared with testis from wildtype mice.
*FIELD* RF
1. Friesen, W. J.; Wyce, A.; Paushkin, S.; Abel, L.; Rappsilbers,
J.; Mann, M.; Dreyfuss, G.: A novel WD repeat protein component of
the methylosome binds Sm proteins. J. Biol. Chem. 277: 8243-8247,
2002.
2. Furuno, K.; Masatsugu, T.; Sonoda, M.; Sasazuki, T.; Yamamoto,
K.: Association of Polycomb group SUZ12 with WD-repeat protein MEP50
that binds to histone H2A selectively in vitro. Biochem. Biophys.
Res. Commun. 345: 1051-1058, 2006.
3. Liang, J. J.; Wang, Z.; Chiriboga, L.; Greco, M. A.; Shapiro, E.;
Huang, H.; Yang, X. J.; Huang, J.; Peng, Y.; Malamed, J.; Garabedian,
M. J.; Lee, P.: The expression and function of androgen receptor
coactivator p44 and protein arginine methyltransferase 5 in the developing
testis and testicular tumors. J. Urology 177: 1918-1922, 2007.
4. Licciardo, P.; Amente, S.; Ruggiero, L.; Monti, M.; Pucci, P.;
Lania, L.; Majello, B.: The FCP1 phosphatase interacts with RNA polymerase
II and with MEP50 a component of the methylosome complex involved
in the assembly of snRNP. Nucleic Acids Res. 31: 999-1005, 2003.
5. Peng, Y.; Chen, F.; Melamed, J.; Chiriboga, L.; Wei, J.; Kong,
X.; Mcleod, M.; Li, Y.; Li, C. X.; Feng, A.; Garabedian, M. J.; Wang,
Z.; Roeder, R. G.; Lee, P.: Distinct nuclear and cytoplasmic functions
of androgen receptor cofactor p44 and association with androgen-independent
prostate cancer. Proc. Nat. Acad. Sci. 105: 5236-5241, 2008.
*FIELD* CN
Patricia A. Hartz - updated: 6/5/2008
*FIELD* CD
Patricia A. Hartz: 1/17/2008
*FIELD* ED
alopez: 06/26/2008
terry: 6/5/2008
mgross: 1/17/2008