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 27-MAR-2024, entry version 208. 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 FUNCTION, INTERACTION WITH MBD2, IDENTIFICATION BY MASS SPECTROMETRY, AND RP SUBCELLULAR LOCATION. RX PubMed=16428440; DOI=10.1128/mcb.26.3.843-851.2006; RA Le Guezennec X., Vermeulen M., Brinkman A.B., Hoeijmakers W.A., Cohen A., RA Lasonder E., Stunnenberg H.G.; RT "MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical RT and functional properties."; RL Mol. Cell. Biol. 26:843-851(2006). RN [23] 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 [24] 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 [25] 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 [26] 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 [27] 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 [28] 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 [29] 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 [30] 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 [31] 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 [32] 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 [33] 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 [34] 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 [35] 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 [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=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 [37] 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 [38] 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 [39] 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 [40] 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 [41] 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 [42] {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). May methylate CC the N-terminal region of MBD2 (PubMed:16428440). Mono- and dimethylates CC arginine residues of myelin basic protein (MBP) in vitro. May play a CC role in cytokine-activated transduction pathways. Negatively regulates CC cyclin E1 promoter activity and cellular proliferation. Methylates CC 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:16428440, ECO:0000269|PubMed:17709427, CC ECO:0000269|PubMed:19011621, ECO:0000269|PubMed:20159986, CC ECO:0000269|PubMed:20421892, 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:25092918, ECO:0000269|PubMed:25284789, CC 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 Interacts with MBD2 (PubMed:16428440). Does not interact with MBD3 CC (PubMed:16428440). {ECO:0000250|UniProtKB:Q8CIG8, CC ECO:0000269|PubMed:10531356, ECO:0000269|PubMed:10734105, CC ECO:0000269|PubMed:11152681, ECO:0000269|PubMed:12411503, CC ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:15485929, CC ECO:0000269|PubMed:15737618, ECO:0000269|PubMed:16087681, CC ECO:0000269|PubMed:16428440, 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; Q9NX04: AIRIM; NbExp=3; IntAct=EBI-351098, EBI-8643161; CC O14744; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-351098, EBI-2837444; 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:16428440, ECO:0000269|PubMed:33376131}. Golgi CC apparatus {ECO:0000269|PubMed:20421892}. Note=Localizes to promoter CC regions of target genes on chromosomes (PubMed:33376131). Localizes to CC methylated chromatin (PubMed:16428440). {ECO:0000269|PubMed:16428440, CC 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7U30; X-ray; 2.60 A; A=2-637. DR PDB; 7UOH; X-ray; 2.70 A; A=2-637. DR PDB; 7UY1; X-ray; 2.66 A; A=2-637. DR PDB; 7UYF; X-ray; 2.82 A; A=2-637. DR PDB; 7ZUP; X-ray; 2.01 A; A=2-637. DR PDB; 7ZUQ; X-ray; 2.48 A; A=2-637. DR PDB; 7ZUU; X-ray; 2.09 A; A=2-637. DR PDB; 7ZUY; X-ray; 2.00 A; A=2-637. DR PDB; 7ZV2; X-ray; 2.01 A; A=2-637. DR PDB; 7ZVL; X-ray; 2.39 A; A=2-637. DR PDB; 7ZVU; X-ray; 1.95 A; A=2-637. DR PDB; 8CSG; X-ray; 2.48 A; A=2-637. DR PDB; 8CTB; X-ray; 2.61 A; A=2-637. DR PDB; 8CYI; EM; 3.14 A; A=1-637. DR PDB; 8G1U; EM; 2.83 A; A/E/I/M=1-637. 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 PDBsum; 7U30; -. DR PDBsum; 7UOH; -. DR PDBsum; 7UY1; -. DR PDBsum; 7UYF; -. DR PDBsum; 7ZUP; -. DR PDBsum; 7ZUQ; -. DR PDBsum; 7ZUU; -. DR PDBsum; 7ZUY; -. DR PDBsum; 7ZV2; -. DR PDBsum; 7ZVL; -. DR PDBsum; 7ZVU; -. DR PDBsum; 8CSG; -. DR PDBsum; 8CTB; -. DR PDBsum; 8CYI; -. DR PDBsum; 8G1U; -. DR AlphaFoldDB; O14744; -. DR EMDB; EMD-20764; -. DR EMDB; EMD-23609; -. DR EMDB; EMD-27078; -. DR EMDB; EMD-29677; -. DR EMDB; EMD-7137; -. DR SMR; O14744; -. DR BioGRID; 115688; 469. DR ComplexPortal; CPX-696; PRMT5 methylosome complex, CLNS1A variant. DR ComplexPortal; CPX-8148; PRMT5 methylosome complex, RIOK1 variant. DR ComplexPortal; CPX-8149; PRMT5 methylosome complex, COPR5 variant. DR CORUM; O14744; -. DR DIP; DIP-33172N; -. DR IntAct; O14744; 158. DR MINT; O14744; -. DR STRING; 9606.ENSP00000319169; -. DR BindingDB; O14744; -. DR ChEMBL; CHEMBL1795116; -. DR GuidetoPHARMACOLOGY; 1256; -. DR GlyGen; O14744; 3 sites, 1 O-linked glycan (3 sites). 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; 9606-ENSP00000319169; -. DR PeptideAtlas; O14744; -. DR ProteomicsDB; 2039; -. DR ProteomicsDB; 48200; -. [O14744-1] DR ProteomicsDB; 48201; -. [O14744-2] DR ProteomicsDB; 5410; -. DR Pumba; O14744; -. DR ABCD; O14744; 6 sequenced antibodies. DR Antibodypedia; 115; 732 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 AGR; HGNC:10894; -. 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; WEFSHPI; -. DR OrthoDB; 5489665at2759; -. DR PhylomeDB; O14744; -. DR TreeFam; TF300626; -. DR BioCyc; MetaCyc:HS02092-MONOMER; -. 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; 746 hits in 1195 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 189 other cell types or tissues. DR ExpressionAtlas; O14744; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:CACAO. DR GO; GO:0005829; C:cytosol; IDA:HPA. 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:0008469; F:histone arginine N-methyltransferase activity; IBA:GO_Central. DR GO; GO:0140938; F:histone H3 methyltransferase activity; TAS:Reactome. DR GO; GO:0044020; F:histone H4R3 methyltransferase activity; IDA:UniProtKB. DR GO; GO:0042054; F:histone methyltransferase activity; TAS:Reactome. 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:0006338; P:chromatin remodeling; IDA:UniProtKB. 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: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:MGI. 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; NAS: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:0006355; P:regulation of DNA-templated transcription; IBA:GO_Central. 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:0000387; P:spliceosomal snRNP assembly; IMP:UniProtKB. DR CDD; cd02440; AdoMet_MTases; 1. DR Gene3D; 3.20.20.150; Divalent-metal-dependent TIM barrel enzymes; 1. DR Gene3D; 2.70.160.11; Hnrnp arginine n-methyltransferase1; 1. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 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; PROTEIN ARGININE N-METHYLTRANSFERASE 5; 1. DR PANTHER; PTHR10738:SF0; PROTEIN ARGININE N-METHYLTRANSFERASE 5; 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; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR PROSITE; PS51678; SAM_MT_PRMT; 1. DR Genevisible; O14744; HS. 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 STRAND 290..292 FT /evidence="ECO:0007829|PDB:7UY1" 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:7ZVU" 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 510..513 FT /evidence="ECO:0007829|PDB:7ZVL" 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 //