ANM5_HUMAN
ID ANM5_HUMAN Reviewed; 637 AA.
AC O14744; A8MTP3; A8MZ91; B4DX49; B4DY30; B5BU10; D3DS33; E2QRE7; Q6IBR1;
AC Q9UKH1;
DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Protein arginine N-methyltransferase 5;
DE Short=PRMT5;
DE EC=2.1.1.320 {ECO:0000269|PubMed:19011621, ECO:0000269|PubMed:21081503, ECO:0000269|PubMed:23071334};
DE AltName: Full=72 kDa ICln-binding protein;
DE AltName: Full=Histone-arginine N-methyltransferase PRMT5;
DE AltName: Full=Jak-binding protein 1;
DE AltName: Full=Shk1 kinase-binding protein 1 homolog;
DE Short=SKB1 homolog;
DE Short=SKB1Hs;
DE Contains:
DE RecName: Full=Protein arginine N-methyltransferase 5, N-terminally processed;
GN Name=PRMT5; Synonyms=HRMT1L5, IBP72, JBP1, SKB1;
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), TISSUE SPECIFICITY, AND INTERACTION
RP WITH CLNS1A.
RX PubMed=9556550; DOI=10.1074/jbc.273.18.10811;
RA Krapivinsky G., Pu W., Wickman K., Krapivinsky L., Clapham D.E.;
RT "pICln binds to a mammalian homolog of a yeast protein involved in
RT regulation of cell morphology.";
RL J. Biol. Chem. 273:10811-10814(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9843966; DOI=10.1073/pnas.95.25.14781;
RA Gilbreth M., Yang P., Bartholomeusz G., Pimental R.A., Kansra S.,
RA Gadiraju R., Marcus S.;
RT "Negative regulation of mitosis in fission yeast by the shk1 interacting
RT protein skb1 and its human homolog, Skb1Hs.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:14781-14786(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND INTERACTION WITH
RP JAK2.
RX PubMed=10531356; DOI=10.1074/jbc.274.44.31531;
RA Pollack B.P., Kotenko S.V., He W., Izotova L.S., Barnoski B.L., Pestka S.;
RT "The human homologue of the yeast proteins Skb1 and Hsl7p interacts with
RT Jak kinases and contains protein methyltransferase activity.";
RL J. Biol. Chem. 274:31531-31542(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 5).
RC TISSUE=Testis, and Thyroid;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [8]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [10]
RP PROTEIN SEQUENCE OF 1-13 AND 594-601, FUNCTION IN THE REGULATION OF
RP MAPK1/MAPK3 SIGNALING PATHWAY, INTERACTION WITH BRAF AND RAF1, ACTIVITY
RP REGULATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 365-GLY--GLY-369.
RX PubMed=21917714; DOI=10.1126/scisignal.2001936;
RA Andreu-Perez P., Esteve-Puig R., de Torre-Minguela C., Lopez-Fauqued M.,
RA Bech-Serra J.J., Tenbaum S., Garcia-Trevijano E.R., Canals F., Merlino G.,
RA Avila M.A., Recio J.A.;
RT "Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction
RT amplitude and cell fate through CRAF.";
RL Sci. Signal. 4:RA58-RA58(2011).
RN [11]
RP PROTEIN SEQUENCE OF 2-13.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [12]
RP FUNCTION, AND SUBUNIT.
RX PubMed=12411503; DOI=10.1093/emboj/cdf585;
RA Meister G., Fischer U.;
RT "Assisted RNP assembly: SMN and PRMT5 complexes cooperate in the formation
RT of spliceosomal UsnRNPs.";
RL EMBO J. 21:5853-5863(2002).
RN [13]
RP FUNCTION, AND INTERACTION WITH EPB41L3.
RX PubMed=15737618; DOI=10.1016/j.bbrc.2005.01.153;
RA Jiang W., Roemer M.E., Newsham I.F.;
RT "The tumor suppressor DAL-1/4.1B modulates protein arginine N-
RT methyltransferase 5 activity in a substrate-specific manner.";
RL Biochem. Biophys. Res. Commun. 329:522-530(2005).
RN [14]
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 [15]
RP PROTEIN SEQUENCE OF 2-13; 19-49; 52-60; 69-95; 155-193; 201-248; 334-343;
RP 349-377; 386-393; 422-428; 459-485 AND 489-526, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Hepatoma, and Mammary carcinoma;
RA Bienvenut W.V., Calvo F., Matallanas D., Cooper W.N., Kolch W., Boldt K.,
RA von Kriegsheim A.F.;
RL Submitted (FEB-2008) to UniProtKB.
RN [16]
RP INTERACTION WITH SSTR1.
RX PubMed=10734105; DOI=10.1074/jbc.275.13.9557;
RA Schwaerzler A., Kreienkamp H.-J., Richter D.;
RT "Interaction of the somatostatin receptor subtype 1 with the human homolog
RT of the Shk1 kinase-binding protein from yeast.";
RL J. Biol. Chem. 275:9557-9562(2000).
RN [17]
RP FUNCTION, AND SUBUNIT.
RX PubMed=11152681; DOI=10.1074/jbc.m008660200;
RA Rho J., Choi S., Seong Y.R., Cho W.-K., Kim S.H., Im D.-S.;
RT "Prmt5, which forms distinct homo-oligomers, is a member of the protein-
RT arginine methyltransferase family.";
RL J. Biol. Chem. 276:11393-11401(2001).
RN [18]
RP FUNCTION IN THE METHYLATION AT SNRPD1 AND SNRPD3.
RX PubMed=11747828; DOI=10.1016/s0960-9822(01)00592-9;
RA Meister G., Eggert C., Buehler D., Brahms H., Kambach C., Fischer U.;
RT "Methylation of Sm proteins by a complex containing PRMT5 and the putative
RT U snRNP assembly factor pICln.";
RL Curr. Biol. 11:1990-1994(2001).
RN [19]
RP COMPONENT OF THE CERC COMPLEX.
RX PubMed=12101096; DOI=10.1093/embo-reports/kvf136;
RA Fabbrizio E., El Messaoudi S., Polanowska J., Paul C., Cook J.R.,
RA Lee J.-H., Negre V., Rousset M., Pestka S., Le Cam A., Sardet C.;
RT "Negative regulation of transcription by the type II arginine
RT methyltransferase PRMT5.";
RL EMBO Rep. 3:641-645(2002).
RN [20]
RP FUNCTION, AND INTERACTION WITH SUPT5H.
RX PubMed=12718890; DOI=10.1016/s1097-2765(03)00101-1;
RA Kwak Y.T., Guo J., Prajapati S., Park K.-J., Surabhi R.M., Miller B.,
RA Gehrig P., Gaynor R.B.;
RT "Methylation of SPT5 regulates its interaction with RNA polymerase II and
RT transcriptional elongation properties.";
RL Mol. Cell 11:1055-1066(2003).
RN [21]
RP INTERACTION WITH THE SWI/SNF COMPLEX, MUTAGENESIS OF 367-GLY-ARG-368, AND
RP METHYLATION OF HISTONE H3.
RX PubMed=15485929; DOI=10.1128/mcb.24.21.9630-9645.2004;
RA Pal S., Vishwanath S.N., Erdjument-Bromage H., Tempst P., Sif S.;
RT "Human SWI/SNF-associated PRMT5 methylates histone H3 arginine 8 and
RT negatively regulates expression of ST7 and NM23 tumor suppressor genes.";
RL Mol. Cell. Biol. 24:9630-9645(2004).
RN [22]
RP INTERACTION WITH IWS1.
RX PubMed=17184735; DOI=10.1016/j.bbrc.2006.11.133;
RA Liu Z., Zhou Z., Chen G., Bao S.;
RT "A putative transcriptional elongation factor hIws1 is essential for
RT mammalian cell proliferation.";
RL Biochem. Biophys. Res. Commun. 353:47-53(2007).
RN [23]
RP FUNCTION, AND INTERACTION WITH PRMT7 AND SNRPD3.
RX PubMed=17709427; DOI=10.1083/jcb.200702147;
RA Gonsalvez G.B., Tian L., Ospina J.K., Boisvert F.-M., Lamond A.I.,
RA Matera A.G.;
RT "Two distinct arginine methyltransferases are required for biogenesis of
RT Sm-class ribonucleoproteins.";
RL J. Cell Biol. 178:733-740(2007).
RN [24]
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 [25]
RP INTERACTION WITH COPRS, AND SUBCELLULAR LOCATION.
RX PubMed=18404153; DOI=10.1038/embor.2008.45;
RA Lacroix M., Messaoudi S.E., Rodier G., Le Cam A., Sardet C., Fabbrizio E.;
RT "The histone-binding protein COPR5 is required for nuclear functions of the
RT protein arginine methyltransferase PRMT5.";
RL EMBO Rep. 9:452-458(2008).
RN [26]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH TTC5 AND TP53.
RX PubMed=19011621; DOI=10.1038/ncb1802;
RA Jansson M., Durant S.T., Cho E.C., Sheahan S., Edelmann M., Kessler B.,
RA La Thangue N.B.;
RT "Arginine methylation regulates the p53 response.";
RL Nat. Cell Biol. 10:1431-1439(2008).
RN [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [28]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20421892; DOI=10.1038/cr.2010.56;
RA Zhou Z., Sun X., Zou Z., Sun L., Zhang T., Guo S., Wen Y., Liu L., Wang Y.,
RA Qin J., Li L., Gong W., Bao S.;
RT "PRMT5 regulates Golgi apparatus structure through methylation of the
RT golgin GM130.";
RL Cell Res. 20:1023-1033(2010).
RN [29]
RP FUNCTION, AND INTERACTION WITH RPS10.
RX PubMed=20159986; DOI=10.1074/jbc.m110.103911;
RA Ren J., Wang Y., Liang Y., Zhang Y., Bao S., Xu Z.;
RT "Methylation of ribosomal protein S10 by protein-arginine methyltransferase
RT 5 regulates ribosome biogenesis.";
RL J. Biol. Chem. 285:12695-12705(2010).
RN [30]
RP FUNCTION IN CELL MIGRATION, AND INTERACTION WITH SRGAP2.
RX PubMed=20810653; DOI=10.1074/jbc.m110.153429;
RA Guo S., Bao S.;
RT "srGAP2 arginine methylation regulates cell migration and cell spreading
RT through promoting dimerization.";
RL J. Biol. Chem. 285:35133-35141(2010).
RN [31]
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 [32]
RP SUBUNIT, SUBCELLULAR LOCATION, INTERACTION WITH RIOK1 AND CLNS1A,
RP IDENTIFICATION IN A COMPLEX WITH PRTM5; WDR77; RIOK1 OR CLNS1A, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
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 [33]
RP FUNCTION IN EGFR SIGNALING, FUNCTION IN EGFR METHYLATION, AND INTERACTION
RP WITH EGFR.
RX PubMed=21258366; DOI=10.1038/ncb2158;
RA Hsu J.M., Chen C.T., Chou C.K., Kuo H.P., Li L.Y., Lin C.Y., Lee H.J.,
RA Wang Y.N., Liu M., Liao H.W., Shi B., Lai C.C., Bedford M.T., Tsai C.H.,
RA Hung M.C.;
RT "Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation
RT negatively modulates EGFR-mediated ERK activation.";
RL Nat. Cell Biol. 13:174-181(2011).
RN [34]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH HOXA9.
RX PubMed=22269951; DOI=10.1128/mcb.05977-11;
RA Bandyopadhyay S., Harris D.P., Adams G.N., Lause G.E., McHugh A.,
RA Tillmaand E.G., Money A., Willard B., Fox P.L., Dicorleto P.E.;
RT "HOXA9 methylation by PRMT5 is essential for endothelial cell expression of
RT leukocyte adhesion molecules.";
RL Mol. Cell. Biol. 32:1202-1213(2012).
RN [35]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [36]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [37]
RP FUNCTION, INTERACTION WITH CHTOP, AND IDENTIFICATION IN THE METHYLOSOME
RP COMPLEX WITH PRMT1 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 [38]
RP FUNCTION, AND INTERACTION WITH LYAR.
RX PubMed=25092918; DOI=10.1093/nar/gku718;
RA Ju J., Wang Y., Liu R., Zhang Y., Xu Z., Wang Y., Wu Y., Liu M.,
RA Cerruti L., Zou F., Ma C., Fang M., Tan R., Jane S.M., Zhao Q.;
RT "Human fetal globin gene expression is regulated by LYAR.";
RL Nucleic Acids Res. 42:9740-9752(2014).
RN [39]
RP FUNCTION, AND INTERACTION WITH POLR2A AND SMN1.
RX PubMed=26700805; DOI=10.1038/nature16469;
RA Yanling Zhao D., Gish G., Braunschweig U., Li Y., Ni Z., Schmitges F.W.,
RA Zhong G., Liu K., Li W., Moffat J., Vedadi M., Min J., Pawson T.J.,
RA Blencowe B.J., Greenblatt J.F.;
RT "SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal
RT domain control termination.";
RL Nature 529:48-53(2016).
RN [40]
RP INTERACTION WITH FAM47E; WDR77 AND STUB1, AND SUBCELLULAR LOCATION.
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 [41] {ECO:0007744|PDB:4GQB}
RP X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) IN COMPLEX WITH WDR77;
RP S-ADENOSYLMETHIONINE ANALOG AND HISTONE H4 PEPTIDE, CATALYTIC ACTIVITY,
RP ACTIVE SITE, SUBSTRATE-BINDING SITES, 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: Arginine methyltransferase that can both catalyze the
CC formation of omega-N monomethylarginine (MMA) and symmetrical
CC dimethylarginine (sDMA), with a preference for the formation of MMA
CC (PubMed:10531356, PubMed:11152681, PubMed:11747828, PubMed:12411503,
CC PubMed:15737618, PubMed:17709427, PubMed:20159986, PubMed:20810653,
CC PubMed:21258366, PubMed:21917714, PubMed:22269951, PubMed:21081503).
CC Specifically mediates the symmetrical dimethylation of arginine
CC residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm
CC D3 (SNRPD3); such methylation being required for the assembly and
CC biogenesis of snRNP core particles (PubMed:12411503, PubMed:11747828,
CC PubMed:17709427). Methylates SUPT5H and may regulate its
CC transcriptional elongation properties (PubMed:12718890). Mono- and
CC dimethylates arginine residues of myelin basic protein (MBP) in vitro.
CC May play a role in cytokine-activated transduction pathways. Negatively
CC regulates cyclin E1 promoter activity and cellular proliferation.
CC Methylates histone H2A and H4 'Arg-3' during germ cell development (By
CC similarity). Methylates histone H3 'Arg-8', which may repress
CC transcription (By similarity). Methylates the Piwi proteins (PIWIL1,
CC PIWIL2 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 (By similarity). Methylates RPS10.
CC Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2
CC levels. First, monomethylates EGFR; this enhances EGFR 'Tyr-1197'
CC phosphorylation and PTPN6 recruitment, eventually leading to reduced
CC SOS1 phosphorylation (PubMed:21917714, PubMed:21258366). Second,
CC methylates RAF1 and probably BRAF, hence destabilizing these 2
CC signaling proteins and reducing their catalytic activity
CC (PubMed:21917714). Required for induction of E-selectin and VCAM-1, on
CC the endothelial cells surface at sites of inflammation. Methylates
CC HOXA9 (PubMed:22269951). Methylates and regulates SRGAP2 which is
CC involved in cell migration and differentiation (PubMed:20810653). Acts
CC as a transcriptional corepressor in CRY1-mediated repression of the
CC core circadian component PER1 by regulating the H4R3 dimethylation at
CC the PER1 promoter (By similarity). Methylates GM130/GOLGA2, regulating
CC Golgi ribbon formation (PubMed:20421892). Methylates H4R3 in genes
CC involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent
CC manner (PubMed:25284789). Symmetrically methylates POLR2A, a
CC modification that allows the recruitment to POLR2A of proteins
CC including SMN1/SMN2 and SETX. This is required for resolving RNA-DNA
CC hybrids created by RNA polymerase II, that form R-loop in transcription
CC terminal regions, an important step in proper transcription termination
CC (PubMed:26700805). Along with LYAR, binds the promoter of gamma-globin
CC HBG1/HBG2 and represses its expression (PubMed:25092918). Symmetrically
CC methylates NCL (PubMed:21081503). Methylates p53/TP53; methylation
CC might possibly affect p53/TP53 target gene specificity
CC (PubMed:19011621). Involved in spliceosome maturation and mRNA splicing
CC in prophase I spermatocytes through the catalysis of the symmetrical
CC arginine dimethylation of SNRPB (small nuclear ribonucleoprotein-
CC associated protein) and the interaction with tudor domain-containing
CC protein TDRD6 (By similarity). {ECO:0000250|UniProtKB:Q8CIG8,
CC ECO:0000269|PubMed:10531356, ECO:0000269|PubMed:11152681,
CC ECO:0000269|PubMed:11747828, ECO:0000269|PubMed:12411503,
CC ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:15737618,
CC ECO:0000269|PubMed:17709427, ECO:0000269|PubMed:19011621,
CC ECO:0000269|PubMed:20159986, ECO:0000269|PubMed:20421892,
CC ECO:0000269|PubMed:20810653, ECO:0000269|PubMed:21081503,
CC ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:21917714,
CC ECO:0000269|PubMed:22269951, ECO:0000269|PubMed:25092918,
CC ECO:0000269|PubMed:25284789, ECO:0000269|PubMed:26700805}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-arginyl-[protein] + 2 S-adenosyl-L-methionine = 2 H(+) +
CC N(omega),N(omega)'-dimethyl-L-arginyl-[protein] + 2 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:48108, Rhea:RHEA-COMP:10532, Rhea:RHEA-
CC COMP:11992, ChEBI:CHEBI:15378, ChEBI:CHEBI:29965, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:88221; EC=2.1.1.320;
CC Evidence={ECO:0000269|PubMed:19011621, ECO:0000269|PubMed:21081503,
CC ECO:0000269|PubMed:23071334};
CC -!- ACTIVITY REGULATION: Activity is increased by EGF, HGF, FGF1 or FGF2
CC treatments, and slightly decreased by NGF treatment.
CC {ECO:0000269|PubMed:21917714}.
CC -!- SUBUNIT: Forms, at least, homodimers and homotetramers
CC (PubMed:11152681). Component of the methylosome complex, composed of
CC PRMT5, WDR77 and CLNS1A (PubMed:21081503, PubMed:23071334,
CC PubMed:33376131). Found in a complex composed of PRMT5, WDR77 and RIOK1
CC (PubMed:21081503). RIOK1 and CLNS1A associate with PRMT5 in a mutually
CC exclusive fashion, which allows the recruitment of distinct methylation
CC substrates, such as nucleolin/NCL and Sm proteins, respectively
CC (PubMed:21081503). Interacts with PRDM1 (By similarity). Identified in
CC a complex composed of methylosome and PRMT1 and ERH (PubMed:25284789).
CC Interacts with EGFR; methylates EGFR and stimulates EGFR-mediated ERK
CC activation. Interacts with HOXA9. Interacts with SRGAP2. Found in a
CC complex with COPRS, RUNX1 and CBFB. Interacts with CHTOP; the
CC interaction symmetrically methylates CHTOP, but seems to require the
CC presence of PRMT1 (PubMed:25284789). Interacts with EPB41L3; this
CC modulates methylation of target proteins. Component of a high molecular
CC weight E2F-pocket protein complex, CERC (cyclin E1 repressor complex).
CC Associates with SWI/SNF remodeling complexes containing SMARCA2 and
CC SMARCA4. Interacts with JAK2, SSTR1, SUPT5H, BRAF and with active RAF1.
CC Interacts with LSM11, PRMT7 and SNRPD3 (PubMed:17709427,
CC PubMed:16087681). Interacts with COPRS; promoting its recruitment on
CC histone H4. Interacts with CLNS1A/pICln (PubMed:21081503,
CC PubMed:9556550). Identified in a complex with CLNS1A/pICln and Sm
CC proteins. Interacts with RPS10 (PubMed:20159986). Interacts with WDR77.
CC Interacts with IWS1. Interacts with CRY1. Interacts with POLR2A
CC (PubMed:26700805). Interacts with SMN1/SMN2 (PubMed:26700805).
CC Interacts with LYAR; this interaction is direct (PubMed:25092918).
CC Interacts with TTC5/STRAP; this interaction is DNA damage-dependent and
CC promotes PRMT5 interaction with p53/TP53 (PubMed:19011621). Interacts
CC with p53/TP53 in response to DNA damage; the interaction is TTC5/STRAP
CC dependent (PubMed:19011621). Interacts with FAM47E; the interaction is
CC direct, promotes PRMT5 localization to chromatin, and does not disrupt
CC its association with WDR77 or STUB1 (PubMed:33376131). Interacts with
CC TDRD6 (By similarity). Interacts with STUB1 (PubMed:33376131).
CC {ECO:0000250|UniProtKB:Q8CIG8, ECO:0000269|PubMed:10531356,
CC ECO:0000269|PubMed:10734105, ECO:0000269|PubMed:11152681,
CC ECO:0000269|PubMed:12411503, ECO:0000269|PubMed:12718890,
CC ECO:0000269|PubMed:15485929, ECO:0000269|PubMed:15737618,
CC ECO:0000269|PubMed:16087681, ECO:0000269|PubMed:17184735,
CC ECO:0000269|PubMed:17709427, ECO:0000269|PubMed:18404153,
CC ECO:0000269|PubMed:18984161, ECO:0000269|PubMed:19011621,
CC ECO:0000269|PubMed:20159986, ECO:0000269|PubMed:20810653,
CC ECO:0000269|PubMed:21081503, ECO:0000269|PubMed:21258366,
CC ECO:0000269|PubMed:21917714, ECO:0000269|PubMed:22269951,
CC ECO:0000269|PubMed:23071334, ECO:0000269|PubMed:25092918,
CC ECO:0000269|PubMed:25284789, ECO:0000269|PubMed:26700805,
CC ECO:0000269|PubMed:33376131, ECO:0000269|PubMed:9556550}.
CC -!- INTERACTION:
CC O14744; P01019: AGT; NbExp=3; IntAct=EBI-351098, EBI-751728;
CC O14744; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-351098, EBI-2837444;
CC O14744; Q9NX04: C1orf109; NbExp=3; IntAct=EBI-351098, EBI-8643161;
CC O14744; Q08289: CACNB2; NbExp=3; IntAct=EBI-351098, EBI-2874501;
CC O14744; P78371: CCT2; NbExp=3; IntAct=EBI-351098, EBI-357407;
CC O14744; Q16543: CDC37; NbExp=3; IntAct=EBI-351098, EBI-295634;
CC O14744; Q8N8U2: CDYL2; NbExp=2; IntAct=EBI-351098, EBI-8467076;
CC O14744; P54105: CLNS1A; NbExp=8; IntAct=EBI-351098, EBI-724693;
CC O14744; P21964-2: COMT; NbExp=3; IntAct=EBI-351098, EBI-10200977;
CC O14744; Q9NQ92: COPRS; NbExp=6; IntAct=EBI-351098, EBI-1642558;
CC O14744; Q16526: CRY1; NbExp=3; IntAct=EBI-351098, EBI-741297;
CC O14744; Q9Y6K1: DNMT3A; NbExp=4; IntAct=EBI-351098, EBI-923653;
CC O14744; Q01094: E2F1; NbExp=8; IntAct=EBI-351098, EBI-448924;
CC O14744; Q08426: EHHADH; NbExp=3; IntAct=EBI-351098, EBI-2339219;
CC O14744; P38919: EIF4A3; NbExp=3; IntAct=EBI-351098, EBI-299104;
CC O14744; Q14241: ELOA; NbExp=3; IntAct=EBI-351098, EBI-742350;
CC O14744; O15197-2: EPHB6; NbExp=3; IntAct=EBI-351098, EBI-10182490;
CC O14744; Q6ZV65: FAM47E; NbExp=2; IntAct=EBI-351098, EBI-26583822;
CC O14744; P01100: FOS; NbExp=3; IntAct=EBI-351098, EBI-852851;
CC O14744; O95995: GAS8; NbExp=3; IntAct=EBI-351098, EBI-1052570;
CC O14744; P62993: GRB2; NbExp=4; IntAct=EBI-351098, EBI-401755;
CC O14744; Q8TE85: GRHL3; NbExp=2; IntAct=EBI-351098, EBI-8469396;
CC O14744; Q9BX10: GTPBP2; NbExp=2; IntAct=EBI-351098, EBI-6115579;
CC O14744; P62805: H4C9; NbExp=6; IntAct=EBI-351098, EBI-302023;
CC O14744; P31269: HOXA9; NbExp=4; IntAct=EBI-351098, EBI-742314;
CC O14744; Q00613: HSF1; NbExp=3; IntAct=EBI-351098, EBI-719620;
CC O14744; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-351098, EBI-2556193;
CC O14744; P03952: KLKB1; NbExp=3; IntAct=EBI-351098, EBI-10087153;
CC O14744; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-351098, EBI-739832;
CC O14744; P06858: LPL; NbExp=3; IntAct=EBI-351098, EBI-715909;
CC O14744; Q86UQ8-1: NFE4; NbExp=2; IntAct=EBI-351098, EBI-15759783;
CC O14744; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-351098, EBI-741158;
CC O14744; Q8WVJ2: NUDCD2; NbExp=2; IntAct=EBI-351098, EBI-1052153;
CC O14744; P24928: POLR2A; NbExp=6; IntAct=EBI-351098, EBI-295301;
CC O14744; O14744: PRMT5; NbExp=3; IntAct=EBI-351098, EBI-351098;
CC O14744; Q86U06: RBM23; NbExp=3; IntAct=EBI-351098, EBI-780319;
CC O14744; Q9BRS2: RIOK1; NbExp=5; IntAct=EBI-351098, EBI-7307838;
CC O14744; O75044: SRGAP2; NbExp=4; IntAct=EBI-351098, EBI-1051034;
CC O14744; Q96RU7: TRIB3; NbExp=2; IntAct=EBI-351098, EBI-492476;
CC O14744; P31930: UQCRC1; NbExp=3; IntAct=EBI-351098, EBI-1052596;
CC O14744; P40337-2: VHL; NbExp=3; IntAct=EBI-351098, EBI-12157263;
CC O14744; Q9BQA1: WDR77; NbExp=17; IntAct=EBI-351098, EBI-1237307;
CC O14744; P63104: YWHAZ; NbExp=2; IntAct=EBI-351098, EBI-347088;
CC O14744; Q96E35: ZMYND19; NbExp=3; IntAct=EBI-351098, EBI-746595;
CC O14744; Q91XC0: Ajuba; Xeno; NbExp=4; IntAct=EBI-351098, EBI-1565930;
CC O14744; P03418: N; Xeno; NbExp=2; IntAct=EBI-351098, EBI-6930799;
CC O14744-1; Q6ZV65-2: FAM47E; NbExp=5; IntAct=EBI-26583938, EBI-26583549;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21081503,
CC ECO:0000269|PubMed:21917714, ECO:0000269|PubMed:22269951}. Nucleus
CC {ECO:0000269|PubMed:18404153, ECO:0000269|PubMed:21081503,
CC ECO:0000269|PubMed:21917714, ECO:0000269|PubMed:22269951}. Chromosome
CC {ECO:0000269|PubMed:33376131}. Golgi apparatus
CC {ECO:0000269|PubMed:20421892}. Note=Localizes to promoter regions of
CC target genes on chromosomes. {ECO:0000269|PubMed:33376131}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Comment=Additional isoforms seems to exist. According to EST
CC sequences.;
CC Name=1;
CC IsoId=O14744-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O14744-2; Sequence=VSP_043382;
CC Name=4;
CC IsoId=O14744-4; Sequence=VSP_043382, VSP_054768;
CC Name=5;
CC IsoId=O14744-5; Sequence=VSP_054685;
CC Name=3;
CC IsoId=O14744-3; Sequence=VSP_043382, VSP_054685;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:9556550}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Protein arginine N-methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU01015}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BC005820; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF015913; AAB66581.1; -; mRNA.
DR EMBL; AF167572; AAF04502.1; -; mRNA.
DR EMBL; AK075251; BAG52095.1; -; mRNA.
DR EMBL; AK301812; BAG63261.1; -; mRNA.
DR EMBL; AK302240; BAG63592.1; -; mRNA.
DR EMBL; CR456741; CAG33022.1; -; mRNA.
DR EMBL; AB451246; BAG70060.1; -; mRNA.
DR EMBL; AB451370; BAG70184.1; -; mRNA.
DR EMBL; AL132780; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW66218.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW66219.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW66220.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW66221.1; -; Genomic_DNA.
DR EMBL; BC005820; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC025979; AAH25979.1; -; mRNA.
DR CCDS; CCDS41922.1; -. [O14744-2]
DR CCDS; CCDS61394.1; -. [O14744-3]
DR CCDS; CCDS61395.1; -. [O14744-4]
DR CCDS; CCDS61396.1; -. [O14744-5]
DR CCDS; CCDS9579.1; -. [O14744-1]
DR PIR; T03842; T03842.
DR RefSeq; NP_001034708.1; NM_001039619.2. [O14744-2]
DR RefSeq; NP_001269882.1; NM_001282953.1. [O14744-3]
DR RefSeq; NP_001269884.1; NM_001282955.1. [O14744-5]
DR RefSeq; NP_001269885.1; NM_001282956.1. [O14744-4]
DR RefSeq; NP_006100.2; NM_006109.4. [O14744-1]
DR PDB; 4GQB; X-ray; 2.06 A; A=1-637.
DR PDB; 4X60; X-ray; 2.35 A; A=2-637.
DR PDB; 4X61; X-ray; 2.85 A; A=2-637.
DR PDB; 4X63; X-ray; 3.05 A; A=2-637.
DR PDB; 5C9Z; X-ray; 2.36 A; A=2-637.
DR PDB; 5EMJ; X-ray; 2.27 A; A=2-637.
DR PDB; 5EMK; X-ray; 2.52 A; A=2-637.
DR PDB; 5EML; X-ray; 2.39 A; A=2-637.
DR PDB; 5EMM; X-ray; 2.37 A; A=2-637.
DR PDB; 5FA5; X-ray; 2.34 A; A=1-637.
DR PDB; 6CKC; X-ray; 2.80 A; A=1-637.
DR PDB; 6K1S; X-ray; 2.60 A; A=2-637.
DR PDB; 6RLL; X-ray; 2.22 A; A=2-637.
DR PDB; 6RLQ; X-ray; 2.53 A; A=2-637.
DR PDB; 6UGH; EM; 3.40 A; A=1-637.
DR PDB; 6UXX; X-ray; 2.69 A; A=2-637.
DR PDB; 6UXY; X-ray; 2.57 A; A=2-637.
DR PDB; 6V0N; X-ray; 2.11 A; A=1-637.
DR PDB; 6V0O; X-ray; 2.86 A; A=1-637.
DR PDB; 6V0P; X-ray; 1.88 A; A=1-637.
DR PDB; 7BO7; X-ray; 2.83 A; AAA=2-637.
DR PDB; 7BOC; X-ray; 2.55 A; A=1-292.
DR PDB; 7KIB; X-ray; 2.52 A; A=2-637.
DR PDB; 7KIC; X-ray; 2.43 A; A=2-637.
DR PDB; 7KID; X-ray; 2.50 A; A=2-637.
DR PDB; 7L1G; X-ray; 2.47 A; A=2-637.
DR PDB; 7M05; EM; 2.39 A; A/C/E/G=1-637.
DR PDB; 7MX7; X-ray; 2.49 A; A=1-637.
DR PDB; 7MXA; X-ray; 2.71 A; A=1-637.
DR PDB; 7MXC; X-ray; 2.41 A; A=1-637.
DR PDB; 7MXG; X-ray; 2.40 A; A/C=1-637.
DR PDB; 7MXN; X-ray; 2.55 A; A=1-637.
DR PDB; 7S0U; X-ray; 2.01 A; A=2-637.
DR PDB; 7S1P; X-ray; 2.21 A; A=2-637.
DR PDB; 7S1Q; X-ray; 2.78 A; A=2-637.
DR PDB; 7S1R; X-ray; 2.10 A; A=2-637.
DR PDB; 7S1S; X-ray; 2.62 A; A=2-637.
DR PDB; 7SER; X-ray; 2.14 A; A=2-637.
DR PDB; 7SES; X-ray; 2.50 A; A=2-637.
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; 7BOC; -.
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; O14744; -.
DR SMR; O14744; -.
DR BioGRID; 115688; 353.
DR ComplexPortal; CPX-696; PRMT5 methylosome complex.
DR CORUM; O14744; -.
DR DIP; DIP-33172N; -.
DR IntAct; O14744; 150.
DR MINT; O14744; -.
DR STRING; 9606.ENSP00000319169; -.
DR BindingDB; O14744; -.
DR ChEMBL; CHEMBL1795116; -.
DR GuidetoPHARMACOLOGY; 1256; -.
DR GlyGen; O14744; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O14744; -.
DR MetOSite; O14744; -.
DR PhosphoSitePlus; O14744; -.
DR SwissPalm; O14744; -.
DR BioMuta; PRMT5; -.
DR EPD; O14744; -.
DR jPOST; O14744; -.
DR MassIVE; O14744; -.
DR MaxQB; O14744; -.
DR PaxDb; O14744; -.
DR PeptideAtlas; O14744; -.
DR PRIDE; O14744; -.
DR ProteomicsDB; 2039; -.
DR ProteomicsDB; 48200; -. [O14744-1]
DR ProteomicsDB; 48201; -. [O14744-2]
DR ProteomicsDB; 5410; -.
DR ABCD; O14744; 6 sequenced antibodies.
DR Antibodypedia; 115; 663 antibodies from 45 providers.
DR DNASU; 10419; -.
DR Ensembl; ENST00000216350.12; ENSP00000216350.8; ENSG00000100462.16. [O14744-3]
DR Ensembl; ENST00000324366.13; ENSP00000319169.8; ENSG00000100462.16. [O14744-1]
DR Ensembl; ENST00000397440.8; ENSP00000380582.4; ENSG00000100462.16. [O14744-4]
DR Ensembl; ENST00000397441.6; ENSP00000380583.2; ENSG00000100462.16. [O14744-2]
DR Ensembl; ENST00000553897.5; ENSP00000452555.1; ENSG00000100462.16. [O14744-5]
DR GeneID; 10419; -.
DR KEGG; hsa:10419; -.
DR MANE-Select; ENST00000324366.13; ENSP00000319169.8; NM_006109.5; NP_006100.2.
DR UCSC; uc001whl.3; human. [O14744-1]
DR CTD; 10419; -.
DR DisGeNET; 10419; -.
DR GeneCards; PRMT5; -.
DR HGNC; HGNC:10894; PRMT5.
DR HPA; ENSG00000100462; Low tissue specificity.
DR MIM; 604045; gene.
DR neXtProt; NX_O14744; -.
DR OpenTargets; ENSG00000100462; -.
DR PharmGKB; PA35794; -.
DR VEuPathDB; HostDB:ENSG00000100462; -.
DR eggNOG; KOG0822; Eukaryota.
DR GeneTree; ENSGT00390000001141; -.
DR HOGENOM; CLU_010247_3_0_1; -.
DR InParanoid; O14744; -.
DR OMA; IKYAWYE; -.
DR OrthoDB; 475852at2759; -.
DR PhylomeDB; O14744; -.
DR TreeFam; TF300626; -.
DR BioCyc; MetaCyc:HS02092-MON; -.
DR BRENDA; 2.1.1.320; 2681.
DR PathwayCommons; O14744; -.
DR Reactome; R-HSA-191859; snRNP Assembly.
DR Reactome; R-HSA-3214858; RMTs methylate histone arginines.
DR Reactome; R-HSA-6804760; Regulation of TP53 Activity through Methylation.
DR SignaLink; O14744; -.
DR SIGNOR; O14744; -.
DR BioGRID-ORCS; 10419; 709 hits in 1114 CRISPR screens.
DR ChiTaRS; PRMT5; human.
DR GeneWiki; Protein_arginine_methyltransferase_5; -.
DR GenomeRNAi; 10419; -.
DR Pharos; O14744; Tchem.
DR PRO; PR:O14744; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; O14744; protein.
DR Bgee; ENSG00000100462; Expressed in ventricular zone and 187 other tissues.
DR ExpressionAtlas; O14744; baseline and differential.
DR Genevisible; O14744; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:CACAO.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0035097; C:histone methyltransferase complex; IDA:ParkinsonsUK-UCL.
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:0070888; F:E-box binding; ISS:UniProtKB.
DR GO; GO:0044020; F:histone methyltransferase activity (H4-R3 specific); IDA:WormBase.
DR GO; GO:0008469; F:histone-arginine N-methyltransferase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008327; F:methyl-CpG binding; IDA:UniProtKB.
DR GO; GO:0008168; F:methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0002039; F:p53 binding; IPI:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:MGI.
DR GO; GO:0016274; F:protein-arginine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0035243; F:protein-arginine omega-N symmetric methyltransferase activity; IDA:WormBase.
DR GO; GO:0043021; F:ribonucleoprotein complex binding; IPI:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0006353; P:DNA-templated transcription, termination; IMP:UniProtKB.
DR GO; GO:0042118; P:endothelial cell activation; IMP:UniProtKB.
DR GO; GO:0090161; P:Golgi ribbon formation; IMP:UniProtKB.
DR GO; GO:0034969; P:histone arginine methylation; IBA:GO_Central.
DR GO; GO:0043985; P:histone H4-R3 methylation; IDA:WormBase.
DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl.
DR GO; GO:0045596; P:negative regulation of cell differentiation; IEA:Ensembl.
DR GO; GO:0018216; P:peptidyl-arginine methylation; IMP:UniProtKB.
DR GO; GO:0035246; P:peptidyl-arginine N-methylation; IDA:WormBase.
DR GO; GO:1904992; P:positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway; IGI:WormBase.
DR GO; GO:0048026; P:positive regulation of mRNA splicing, via spliceosome; IC:ComplexPortal.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0044030; P:regulation of DNA methylation; IEA:Ensembl.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0007088; P:regulation of mitotic nuclear division; TAS:ProtInc.
DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0000387; P:spliceosomal snRNP assembly; IMP:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR IDEAL; IID00405; -.
DR InterPro; IPR025799; Arg_MeTrfase.
DR InterPro; IPR007857; Arg_MeTrfase_PRMT5.
DR InterPro; IPR035075; PRMT5.
DR InterPro; IPR035248; PRMT5_C.
DR InterPro; IPR035247; PRMT5_TIM.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR10738; PTHR10738; 1.
DR Pfam; PF05185; PRMT5; 1.
DR Pfam; PF17286; PRMT5_C; 1.
DR Pfam; PF17285; PRMT5_TIM; 1.
DR PIRSF; PIRSF015894; Skb1_MeTrfase; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51678; SAM_MT_PRMT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Biological rhythms;
KW Chromatin regulator; Chromosome; Cytoplasm; Direct protein sequencing;
KW Golgi apparatus; Methyltransferase; Nucleus; Reference proteome; Repressor;
KW S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW Transferase.
FT CHAIN 1..637
FT /note="Protein arginine N-methyltransferase 5"
FT /id="PRO_0000212342"
FT INIT_MET 1
FT /note="Removed; alternate"
FT /evidence="ECO:0000269|PubMed:12665801, ECO:0000269|Ref.15,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..637
FT /note="Protein arginine N-methyltransferase 5, N-terminally
FT processed"
FT /id="PRO_0000417602"
FT DOMAIN 308..615
FT /note="SAM-dependent MTase PRMT-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01015"
FT REGION 13..292
FT /note="TIM barrel"
FT /evidence="ECO:0000269|PubMed:23071334"
FT REGION 465..637
FT /note="Beta barrel"
FT /evidence="ECO:0000269|PubMed:23071334"
FT REGION 488..494
FT /note="Dimerization"
FT /evidence="ECO:0000269|PubMed:23071334"
FT ACT_SITE 435
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:23071334"
FT ACT_SITE 444
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:23071334"
FT BINDING 324
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:23071334"
FT BINDING 327
FT /ligand="a protein"
FT /ligand_id="ChEBI:CHEBI:16541"
FT /ligand_note="substrate"
FT /ligand_part="L-arginine residue"
FT /ligand_part_id="ChEBI:CHEBI:29965"
FT /evidence="ECO:0000269|PubMed:23071334"
FT BINDING 333..334
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:23071334"
FT BINDING 392
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:23071334"
FT BINDING 419..420
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:23071334"
FT BINDING 435
FT /ligand="a protein"
FT /ligand_id="ChEBI:CHEBI:16541"
FT /ligand_note="substrate"
FT /ligand_part="L-arginine residue"
FT /ligand_part_id="ChEBI:CHEBI:29965"
FT /evidence="ECO:0000269|PubMed:23071334"
FT BINDING 444
FT /ligand="a protein"
FT /ligand_id="ChEBI:CHEBI:16541"
FT /ligand_note="substrate"
FT /ligand_part="L-arginine residue"
FT /ligand_part_id="ChEBI:CHEBI:29965"
FT /evidence="ECO:0000269|PubMed:23071334"
FT SITE 327
FT /note="Critical for specifying symmetric addition of methyl
FT groups"
FT /evidence="ECO:0000250|UniProtKB:P46580"
FT MOD_RES 2
FT /note="N-acetylalanine; in Protein arginine N-
FT methyltransferase 5, N-terminally processed"
FT /evidence="ECO:0000269|Ref.15, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT VAR_SEQ 1..34
FT /note="MAAMAVGGAGGSRVSSGRDLNCVPEIADTLGAVA -> MRGPNSGTEKGRLV
FT IPE (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.5"
FT /id="VSP_043382"
FT VAR_SEQ 77..120
FT /note="Missing (in isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054685"
FT VAR_SEQ 106..259
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_054768"
FT MUTAGEN 365..369
FT /note="Missing: Increased MAPK1/MAPK3 phosphorylation in
FT response to EGF."
FT /evidence="ECO:0000269|PubMed:21917714"
FT MUTAGEN 367..368
FT /note="GR->AA: Abolishes enzymatic activity."
FT /evidence="ECO:0000269|PubMed:15485929"
FT CONFLICT 183
FT /note="E -> K (in Ref. 4; BAG63592)"
FT /evidence="ECO:0000305"
FT CONFLICT 247
FT /note="S -> F (in Ref. 2; AAB66581)"
FT /evidence="ECO:0000305"
FT CONFLICT 420
FT /note="M -> T (in Ref. 4; BAG63592)"
FT /evidence="ECO:0000305"
FT CONFLICT 553
FT /note="G -> V (in Ref. 2; AAB66581)"
FT /evidence="ECO:0000305"
FT STRAND 16..19
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 26..35
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 39..46
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 54..56
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 75..81
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 97..117
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 120..125
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 132..142
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:6RLL"
FT STRAND 150..158
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:7KIC"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 184..195
FT /evidence="ECO:0007829|PDB:6V0P"
FT TURN 196..198
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 202..207
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 215..220
FT /evidence="ECO:0007829|PDB:6V0P"
FT TURN 221..223
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 226..232
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 233..235
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 236..238
FT /evidence="ECO:0007829|PDB:7BOC"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:7M05"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:7BOC"
FT HELIX 248..259
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 263..268
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 273..275
FT /evidence="ECO:0007829|PDB:4GQB"
FT HELIX 278..289
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 296..300
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 302..304
FT /evidence="ECO:0007829|PDB:7S1R"
FT STRAND 309..311
FT /evidence="ECO:0007829|PDB:4GQB"
FT TURN 314..316
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 321..328
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 331..348
FT /evidence="ECO:0007829|PDB:6V0P"
FT TURN 351..356
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 358..365
FT /evidence="ECO:0007829|PDB:6V0P"
FT TURN 367..369
FT /evidence="ECO:0007829|PDB:5EMK"
FT HELIX 370..382
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 385..392
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 395..407
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 410..412
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 413..418
FT /evidence="ECO:0007829|PDB:6V0P"
FT TURN 420..422
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 429..434
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 436..441
FT /evidence="ECO:0007829|PDB:6UXX"
FT HELIX 442..444
FT /evidence="ECO:0007829|PDB:4GQB"
FT HELIX 446..452
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 454..456
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 457..465
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 467..476
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 478..485
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 490..492
FT /evidence="ECO:0007829|PDB:7M05"
FT HELIX 496..498
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 502..505
FT /evidence="ECO:0007829|PDB:5EMJ"
FT TURN 506..508
FT /evidence="ECO:0007829|PDB:6UXY"
FT STRAND 509..511
FT /evidence="ECO:0007829|PDB:6UXY"
FT STRAND 516..524
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 527..529
FT /evidence="ECO:0007829|PDB:5FA5"
FT STRAND 534..541
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 546..560
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 563..566
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 569..571
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 582..592
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 597..606
FT /evidence="ECO:0007829|PDB:6V0P"
FT STRAND 608..621
FT /evidence="ECO:0007829|PDB:6V0P"
FT HELIX 628..630
FT /evidence="ECO:0007829|PDB:6V0P"
SQ SEQUENCE 637 AA; 72684 MW; 522E255B384F25E7 CRC64;
MAAMAVGGAG GSRVSSGRDL NCVPEIADTL GAVAKQGFDF LCMPVFHPRF KREFIQEPAK
NRPGPQTRSD LLLSGRDWNT LIVGKLSPWI RPDSKVEKIR RNSEAAMLQE LNFGAYLGLP
AFLLPLNQED NTNLARVLTN HIHTGHHSSM FWMRVPLVAP EDLRDDIIEN APTTHTEEYS
GEEKTWMWWH NFRTLCDYSK RIAVALEIGA DLPSNHVIDR WLGEPIKAAI LPTSIFLTNK
KGFPVLSKMH QRLIFRLLKL EVQFIITGTN HHSEKEFCSY LQYLEYLSQN RPPPNAYELF
AKGYEDYLQS PLQPLMDNLE SQTYEVFEKD PIKYSQYQQA IYKCLLDRVP EEEKDTNVQV
LMVLGAGRGP LVNASLRAAK QADRRIKLYA VEKNPNAVVT LENWQFEEWG SQVTVVSSDM
REWVAPEKAD IIVSELLGSF ADNELSPECL DGAQHFLKDD GVSIPGEYTS FLAPISSSKL
YNEVRACREK DRDPEAQFEM PYVVRLHNFH QLSAPQPCFT FSHPNRDPMI DNNRYCTLEF
PVEVNTVLHG FAGYFETVLY QDITLSIRPE THSPGMFSWF PILFPIKQPI TVREGQTICV
RFWRCSNSKK VWYEWAVTAP VCSAIHNPTG RSYTIGL
