ID NSUN2_HUMAN Reviewed; 767 AA. AC Q08J23; A8K529; B2RNR4; B3KP09; B4DQW2; G3V1R4; Q9BVN4; Q9H858; Q9NXD9; DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 29-MAY-2007, sequence version 2. DT 02-DEC-2020, entry version 143. DE RecName: Full=RNA cytosine C(5)-methyltransferase NSUN2 {ECO:0000305}; DE EC=2.1.1.- {ECO:0000269|PubMed:17071714, ECO:0000269|PubMed:22395603, ECO:0000269|PubMed:31186410, ECO:0000269|PubMed:31276587, ECO:0000269|PubMed:31358969}; DE AltName: Full=Myc-induced SUN domain-containing protein {ECO:0000303|PubMed:19596847}; DE Short=Misu {ECO:0000303|PubMed:19596847}; DE AltName: Full=NOL1/NOP2/Sun domain family member 2 {ECO:0000303|PubMed:17215513}; DE AltName: Full=Substrate of AIM1/Aurora kinase B {ECO:0000303|PubMed:17215513}; DE AltName: Full=mRNA cytosine C(5)-methyltransferase; DE EC=2.1.1.- {ECO:0000269|PubMed:22395603, ECO:0000269|PubMed:28418038, ECO:0000269|PubMed:31358969}; DE AltName: Full=tRNA cytosine C(5)-methyltransferase; DE EC=2.1.1.- {ECO:0000269|PubMed:31276587}; DE EC=2.1.1.203 {ECO:0000269|PubMed:17071714}; DE AltName: Full=tRNA methyltransferase 4 homolog {ECO:0000303|PubMed:17071714}; DE Short=hTrm4 {ECO:0000303|PubMed:17071714}; GN Name=NSUN2 {ECO:0000303|PubMed:17215513, ECO:0000312|HGNC:HGNC:25994}; GN Synonyms=SAKI {ECO:0000303|PubMed:17215513}, GN TRM4 {ECO:0000303|PubMed:17071714}; 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), PARTIAL PROTEIN SEQUENCE, RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-139, INTERACTION WITH NPM1 AND RP NCL, AND MUTAGENESIS OF SER-139. RX PubMed=17215513; DOI=10.1091/mbc.e06-11-1021; RA Sakita-Suto S., Kanda A., Suzuki F., Sato S., Takata T., Tatsuka M.; RT "Aurora-B regulates RNA methyltransferase NSUN2."; RL Mol. Biol. Cell 18:1107-1117(2007). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung, and Placenta; 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 [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-743 AND SER-751, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-743 AND SER-751, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY. RX PubMed=17071714; DOI=10.1093/nar/gkl765; RA Brzezicha B., Schmidt M., Makalowska I., Jarmolowski A., Pienkowska J., RA Szweykowska-Kulinska Z.; RT "Identification of human tRNA:m5C methyltransferase catalysing intron- RT dependent m5C formation in the first position of the anticodon of the pre- RT tRNA Leu (CAA)."; RL Nucleic Acids Res. 34:6034-6043(2006). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-743 AND SER-751, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456; SER-473; SER-743 AND RP SER-751, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [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 [12] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19596847; DOI=10.1083/jcb.200810180; RA Hussain S., Benavente S.B., Nascimento E., Dragoni I., Kurowski A., RA Gillich A., Humphreys P., Frye M.; RT "The nucleolar RNA methyltransferase Misu (NSun2) is required for mitotic RT spindle stability."; RL J. Cell Biol. 186:27-40(2009). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-743 AND SER-751, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456; SER-593 AND SER-743, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [15] 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 [16] RP MALONYLATION AT LYS-586. RX PubMed=21908771; DOI=10.1074/mcp.m111.012658; RA Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y., He W., RA Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C., Dai J., RA Verdin E., Ye Y., Zhao Y.; RT "The first identification of lysine malonylation substrates and its RT regulatory enzyme."; RL Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-473 AND SER-593, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [18] RP INVOLVEMENT IN MRT5, AND TISSUE SPECIFICITY. RX PubMed=22541559; DOI=10.1016/j.ajhg.2012.03.021; RA Abbasi-Moheb L., Mertel S., Gonsior M., Nouri-Vahid L., Kahrizi K., RA Cirak S., Wieczorek D., Motazacker M.M., Esmaeeli-Nieh S., Cremer K., RA Weissmann R., Tzschach A., Garshasbi M., Abedini S.S., Najmabadi H., RA Ropers H.H., Sigrist S.J., Kuss A.W.; RT "Mutations in NSUN2 cause autosomal-recessive intellectual disability."; RL Am. J. Hum. Genet. 90:847-855(2012). RN [19] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=22395603; DOI=10.1038/ncomms1692; RA Zhang X., Liu Z., Yi J., Tang H., Xing J., Yu M., Tong T., Shang Y., RA Gorospe M., Wang W.; RT "The tRNA methyltransferase NSun2 stabilizes p16INK[4] mRNA by methylating RT the 3'-untranslated region of p16."; RL Nat. Commun. 3:712-712(2012). RN [20] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=22995836; DOI=10.4161/rna.22180; RA Auxilien S., Guerineau V., Szweykowska-Kulinska Z., Golinelli-Pimpaneau B.; RT "The human tRNA m (5) C methyltransferase Misu is multisite-specific."; RL RNA Biol. 9:1331-1338(2012). RN [21] RP FUNCTION. RX PubMed=23871666; DOI=10.1016/j.celrep.2013.06.029; RA Hussain S., Sajini A.A., Blanco S., Dietmann S., Lombard P., Sugimoto Y., RA Paramor M., Gleeson J.G., Odom D.T., Ule J., Frye M.; RT "NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines RT its processing into regulatory small RNAs."; RL Cell Rep. 4:255-261(2013). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456; SER-593; SER-743 AND RP SER-751, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-456; SER-743 AND SER-751, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [24] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-640, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [25] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF CYS-271 AND RP CYS-321. RX PubMed=28418038; DOI=10.1038/cr.2017.55; RA Yang X., Yang Y., Sun B.F., Chen Y.S., Xu J.W., Lai W.Y., Li A., Wang X., RA Bhattarai D.P., Xiao W., Sun H.Y., Zhu Q., Ma H.L., Adhikari S., Sun M., RA Hao Y.J., Zhang B., Huang C.M., Huang N., Jiang G.B., Zhao Y.L., Wang H.L., RA Sun Y.P., Yang Y.G.; RT "5-methylcytosine promotes mRNA export - NSUN2 as the methyltransferase and RT ALYREF as an m5C reader."; RL Cell Res. 27:606-625(2017). RN [26] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-46; LYS-464; LYS-470; LYS-511; RP LYS-516; LYS-586; LYS-654 AND LYS-660, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [27] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF CYS-271 AND RP CYS-321. RX PubMed=31358969; DOI=10.1038/s41556-019-0361-y; RA Chen X., Li A., Sun B.F., Yang Y., Han Y.N., Yuan X., Chen R.X., Wei W.S., RA Liu Y., Gao C.C., Chen Y.S., Zhang M., Ma X.D., Liu Z.W., Luo J.H., Lyu C., RA Wang H.L., Ma J., Zhao Y.L., Zhou F.J., Huang Y., Xie D., Yang Y.G.; RT "5-methylcytosine promotes pathogenesis of bladder cancer through RT stabilizing mRNAs."; RL Nat. Cell Biol. 21:978-990(2019). RN [28] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-190. RX PubMed=31186410; DOI=10.1038/s41467-019-10020-7; RA Sajini A.A., Choudhury N.R., Wagner R.E., Borneloev S., Selmi T., RA Spanos C., Dietmann S., Rappsilber J., Michlewski G., Frye M.; RT "Loss of 5-methylcytosine alters the biogenesis of vault-derived small RNAs RT to coordinate epidermal differentiation."; RL Nat. Commun. 10:2550-2550(2019). RN [29] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=31276587; DOI=10.1093/nar/gkz559; RA Van Haute L., Lee S.Y., McCann B.J., Powell C.A., Bansal D., RA Vasiliauskaite L., Garone C., Shin S., Kim J.S., Frye M., Gleeson J.G., RA Miska E.A., Rhee H.W., Minczuk M.; RT "NSUN2 introduces 5-methylcytosines in mammalian mitochondrial tRNAs."; RL Nucleic Acids Res. 0:0-0(2019). RN [30] RP SUBCELLULAR LOCATION. RX PubMed=31287866; DOI=10.1093/nar/gkz575; RA Shinoda S., Kitagawa S., Nakagawa S., Wei F.Y., Tomizawa K., Araki K., RA Araki M., Suzuki T., Suzuki T.; RT "Mammalian NSUN2 introduces 5-methylcytidines into mitochondrial tRNAs."; RL Nucleic Acids Res. 0:0-0(2019). RN [31] RP FUNCTION, AND MUTAGENESIS OF LYS-190. RX PubMed=31199786; DOI=10.1371/journal.pbio.3000297; RA Gkatza N.A., Castro C., Harvey R.F., Heiss M., Popis M.C., Blanco S., RA Borneloev S., Sajini A.A., Gleeson J.G., Griffin J.L., West J.A., RA Kellner S., Willis A.E., Dietmann S., Frye M.; RT "Cytosine-5 RNA methylation links protein synthesis to cell metabolism."; RL PLoS Biol. 17:E3000297-E3000297(2019). RN [32] RP VARIANT MRT5 ARG-679, AND CHARACTERIZATION OF VARIANT MRT5 ARG-679. RX PubMed=22541562; DOI=10.1016/j.ajhg.2012.03.023; RA Khan M.A., Rafiq M.A., Noor A., Hussain S., Flores J.V., Rupp V., RA Vincent A.K., Malli R., Ali G., Khan F.S., Ishak G.E., Doherty D., RA Weksberg R., Ayub M., Windpassinger C., Ibrahim S., Frye M., Ansar M., RA Vincent J.B.; RT "Mutation in NSUN2, which encodes an RNA methyltransferase, causes RT autosomal-recessive intellectual disability."; RL Am. J. Hum. Genet. 90:856-863(2012). CC -!- FUNCTION: RNA cytosine C(5)-methyltransferase that methylates cytosine CC to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and CC some long non-coding RNAs (lncRNAs) (PubMed:17071714, PubMed:22995836, CC PubMed:31358969, PubMed:31199786). Involved in various processes, such CC as epidermal stem cell differentiation, testis differentiation and CC maternal to zygotic transition during early development: acts by CC increasing protein synthesis; cytosine C(5)-methylation promoting tRNA CC stability and preventing mRNA decay (PubMed:31199786). Methylates CC cytosine to 5-methylcytosine (m5C) at positions 34 and 48 of intron- CC containing tRNA(Leu)(CAA) precursors, and at positions 48, 49 and 50 of CC tRNA(Gly)(GCC) precursors (PubMed:17071714, PubMed:22995836, CC PubMed:31199786). tRNA methylation is required generation of RNA CC fragments derived from tRNAs (tRFs) (PubMed:31199786). Also mediates CC C(5)-methylation of mitochondrial tRNAs (PubMed:31276587). Catalyzes CC cytosine C(5)-methylation of mRNAs, leading to stabilize them and CC prevent mRNA decay: mRNA stabilization involves YBX1 that specifically CC recognizes and binds m5C-modified transcripts (PubMed:22395603, CC PubMed:31358969). Cytosine C(5)-methylation of mRNAs also regulates CC mRNA export: methylated transcripts are specifically recognized by CC THOC4/ALYREF, which mediates mRNA nucleo-cytoplasmic shuttling CC (PubMed:28418038). Also mediates cytosine C(5)-methylation of non- CC coding RNAs, such as vault RNAs (vtRNAs), promoting their processing CC into regulatory small RNAs (PubMed:23871666). Cytosine C(5)-methylation CC of vtRNA VTRNA1.1 promotes its processing into small-vault RNA4 CC (svRNA4) and regulates epidermal differentiation (PubMed:31186410). May CC act downstream of Myc to regulate epidermal cell growth and CC proliferation (By similarity). Required for proper spindle assembly and CC chromosome segregation, independently of its methyltransferase activity CC (PubMed:19596847). {ECO:0000250|UniProtKB:Q1HFZ0, CC ECO:0000269|PubMed:17071714, ECO:0000269|PubMed:19596847, CC ECO:0000269|PubMed:22395603, ECO:0000269|PubMed:22995836, CC ECO:0000269|PubMed:23871666, ECO:0000269|PubMed:28418038, CC ECO:0000269|PubMed:31186410, ECO:0000269|PubMed:31199786, CC ECO:0000269|PubMed:31276587, ECO:0000269|PubMed:31358969}. CC -!- CATALYTIC ACTIVITY: CC Reaction=cytidine(48) in tRNA + S-adenosyl-L-methionine = 5- CC methylcytidine(48) in tRNA + H(+) + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:42948, Rhea:RHEA-COMP:10293, Rhea:RHEA-COMP:10297, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, CC ChEBI:CHEBI:74483, ChEBI:CHEBI:82748; CC Evidence={ECO:0000269|PubMed:31276587}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42949; CC Evidence={ECO:0000269|PubMed:31276587}; CC -!- CATALYTIC ACTIVITY: CC Reaction=cytidine(49) in tRNA + S-adenosyl-L-methionine = 5- CC methylcytidine(49) in tRNA + H(+) + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:42952, Rhea:RHEA-COMP:10294, Rhea:RHEA-COMP:10385, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, CC ChEBI:CHEBI:74483, ChEBI:CHEBI:82748; CC Evidence={ECO:0000269|PubMed:31276587}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42953; CC Evidence={ECO:0000269|PubMed:31276587}; CC -!- CATALYTIC ACTIVITY: CC Reaction=cytidine(50) in tRNA + S-adenosyl-L-methionine = 5- CC methylcytidine(50) in tRNA + H(+) + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:61488, Rhea:RHEA-COMP:15838, Rhea:RHEA-COMP:15839, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, CC ChEBI:CHEBI:74483, ChEBI:CHEBI:82748; CC Evidence={ECO:0000269|PubMed:31276587}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61489; CC Evidence={ECO:0000269|PubMed:31276587}; CC -!- CATALYTIC ACTIVITY: CC Reaction=cytidine(34) in tRNA precursor + S-adenosyl-L-methionine = 5- CC methylcytidine(34) in tRNA precursor + H(+) + S-adenosyl-L- CC homocysteine; Xref=Rhea:RHEA:42940, Rhea:RHEA-COMP:10291, Rhea:RHEA- CC COMP:10295, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, CC ChEBI:CHEBI:74483, ChEBI:CHEBI:82748; EC=2.1.1.203; CC Evidence={ECO:0000269|PubMed:17071714}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42941; CC Evidence={ECO:0000269|PubMed:17071714}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a cytidine in mRNA + S-adenosyl-L-methionine = a 5- CC methylcytidine in mRNA + H(+) + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:61464, Rhea:RHEA-COMP:15145, Rhea:RHEA-COMP:15826, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, CC ChEBI:CHEBI:74483, ChEBI:CHEBI:82748; CC Evidence={ECO:0000269|PubMed:22395603, ECO:0000269|PubMed:28418038, CC ECO:0000269|PubMed:31358969}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61465; CC Evidence={ECO:0000269|PubMed:22395603, ECO:0000269|PubMed:28418038, CC ECO:0000269|PubMed:31358969}; CC -!- ACTIVITY REGULATION: Inhibited by magnesium ions. CC {ECO:0000269|PubMed:22995836}. CC -!- SUBUNIT: Interacts with NPM1 and NCL during interphase; interaction is CC disrupted following phosphorylation at Ser-139. CC {ECO:0000269|PubMed:17215513}. CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:17071714, CC ECO:0000269|PubMed:17215513, ECO:0000269|PubMed:31276587}. Cytoplasm CC {ECO:0000269|PubMed:17071714, ECO:0000269|PubMed:31276587}. CC Mitochondrion {ECO:0000269|PubMed:31276587, CC ECO:0000269|PubMed:31287866}. Cytoplasm, cytoskeleton, spindle CC {ECO:0000269|PubMed:19596847}. Secreted, extracellular exosome CC {ECO:0000250|UniProtKB:Q1HFZ0}. Note=Concentrated in the nucleolus CC during interphase and translocates to the spindle during mitosis as an CC RNA-protein complex that includes 18S ribosomal RNA (PubMed:19596847). CC In testis, localizes to the chromatoid body (By similarity). CC {ECO:0000250|UniProtKB:Q1HFZ0, ECO:0000269|PubMed:19596847}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q08J23-1; Sequence=Displayed; CC Name=2; CC IsoId=Q08J23-2; Sequence=VSP_042621; CC Name=3; CC IsoId=Q08J23-3; Sequence=VSP_053598; CC -!- TISSUE SPECIFICITY: Expressed in adult and fetal brain and in CC lymphoblastoid cells. {ECO:0000269|PubMed:22541559}. CC -!- PTM: Phosphorylated at Ser-139 by AURKB during mitosis, leading to CC abolish methyltransferase activity and the interaction with NPM1. CC {ECO:0000269|PubMed:17215513}. CC -!- DISEASE: Mental retardation, autosomal recessive 5 (MRT5) [MIM:611091]: CC A disorder characterized by significantly below average general CC intellectual functioning associated with impairments in adaptive CC behavior and manifested during the developmental period. CC {ECO:0000269|PubMed:22541559, ECO:0000269|PubMed:22541562}. Note=The CC disease is caused by mutations affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase CC superfamily. RsmB/NOP family. TRM4 subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU01023}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA91075.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB14762.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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; AB255451; BAF34150.1; -; mRNA. DR EMBL; AK000310; BAA91075.1; ALT_INIT; mRNA. DR EMBL; AK023994; BAB14762.1; ALT_INIT; mRNA. DR EMBL; AK055456; BAG51521.1; -; mRNA. DR EMBL; AK291144; BAF83833.1; -; mRNA. DR EMBL; AK298980; BAG61074.1; -; mRNA. DR EMBL; AC010366; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC027334; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471102; EAX08105.1; -; Genomic_DNA. DR EMBL; CH471102; EAX08106.1; -; Genomic_DNA. DR EMBL; BC001041; AAH01041.3; -; mRNA. DR EMBL; BC137083; AAI37084.1; -; mRNA. DR CCDS; CCDS3869.1; -. [Q08J23-1] DR CCDS; CCDS54832.1; -. [Q08J23-2] DR RefSeq; NP_001180384.1; NM_001193455.1. [Q08J23-2] DR RefSeq; NP_060225.4; NM_017755.5. [Q08J23-1] DR SMR; Q08J23; -. DR BioGRID; 120236; 131. DR DIP; DIP-52456N; -. DR IntAct; Q08J23; 56. DR MINT; Q08J23; -. DR STRING; 9606.ENSP00000264670; -. DR GlyConnect; 1859; 1 N-Linked glycan (1 site). DR GlyGen; Q08J23; 1 site. DR iPTMnet; Q08J23; -. DR MetOSite; Q08J23; -. DR PhosphoSitePlus; Q08J23; -. DR SwissPalm; Q08J23; -. DR BioMuta; NSUN2; -. DR DMDM; 148887180; -. DR CPTAC; CPTAC-984; -. DR EPD; Q08J23; -. DR jPOST; Q08J23; -. DR MassIVE; Q08J23; -. DR MaxQB; Q08J23; -. DR PaxDb; Q08J23; -. DR PeptideAtlas; Q08J23; -. DR PRIDE; Q08J23; -. DR ProteomicsDB; 32415; -. DR ProteomicsDB; 58697; -. [Q08J23-1] DR ProteomicsDB; 58698; -. [Q08J23-2] DR Antibodypedia; 22399; 167 antibodies. DR Ensembl; ENST00000264670; ENSP00000264670; ENSG00000037474. [Q08J23-1] DR Ensembl; ENST00000506139; ENSP00000420957; ENSG00000037474. [Q08J23-2] DR GeneID; 54888; -. DR KEGG; hsa:54888; -. DR UCSC; uc003jdu.4; human. [Q08J23-1] DR CTD; 54888; -. DR DisGeNET; 54888; -. DR EuPathDB; HostDB:ENSG00000037474.14; -. DR GeneCards; NSUN2; -. DR HGNC; HGNC:25994; NSUN2. DR HPA; ENSG00000037474; Low tissue specificity. DR MalaCards; NSUN2; -. DR MIM; 610916; gene. DR MIM; 611091; phenotype. DR neXtProt; NX_Q08J23; -. DR OpenTargets; ENSG00000037474; -. DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability. DR Orphanet; 235; Dubowitz syndrome. DR PharmGKB; PA134953940; -. DR eggNOG; KOG2198; Eukaryota. DR GeneTree; ENSGT00940000153665; -. DR HOGENOM; CLU_005316_4_3_1; -. DR InParanoid; Q08J23; -. DR OMA; GIQYRIV; -. DR OrthoDB; 911098at2759; -. DR PhylomeDB; Q08J23; -. DR TreeFam; TF300702; -. DR BioCyc; MetaCyc:HS12087-MONOMER; -. DR BRENDA; 2.1.1.203; 2681. DR PathwayCommons; Q08J23; -. DR Reactome; R-HSA-6782315; tRNA modification in the nucleus and cytosol. DR SIGNOR; Q08J23; -. DR BioGRID-ORCS; 54888; 10 hits in 854 CRISPR screens. DR ChiTaRS; NSUN2; human. DR GeneWiki; NSUN2; -. DR GenomeRNAi; 54888; -. DR Pharos; Q08J23; Tbio. DR PRO; PR:Q08J23; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q08J23; protein. DR Bgee; ENSG00000037474; Expressed in left lobe of thyroid gland and 215 other tissues. DR ExpressionAtlas; Q08J23; baseline and differential. DR Genevisible; Q08J23; HS. DR GO; GO:0033391; C:chromatoid body; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell. DR GO; GO:0008168; F:methyltransferase activity; IBA:GO_Central. DR GO; GO:0062152; F:mRNA (cytidine-5-)-methyltransferase activity; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0016428; F:tRNA (cytosine-5-)-methyltransferase activity; IDA:UniProtKB. DR GO; GO:0000049; F:tRNA binding; IBA:GO_Central. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0048820; P:hair follicle maturation; ISS:UniProtKB. DR GO; GO:0033313; P:meiotic cell cycle checkpoint; IEA:Ensembl. DR GO; GO:0080009; P:mRNA methylation; IDA:UniProtKB. DR GO; GO:0010793; P:regulation of mRNA export from nucleus; IDA:UniProtKB. DR GO; GO:2000736; P:regulation of stem cell differentiation; ISS:UniProtKB. DR GO; GO:0001510; P:RNA methylation; IBA:GO_Central. DR GO; GO:0007286; P:spermatid development; IEA:Ensembl. DR GO; GO:0030488; P:tRNA methylation; IDA:UniProtKB. DR GO; GO:0006400; P:tRNA modification; TAS:Reactome. DR GO; GO:0036416; P:tRNA stabilization; ISS:UniProtKB. DR InterPro; IPR001678; MeTrfase_RsmB/NOP2. DR InterPro; IPR023267; RCMT. DR InterPro; IPR023270; RCMT_NCL1. DR InterPro; IPR029063; SAM-dependent_MTases. DR Pfam; PF01189; Methyltr_RsmB-F; 1. DR PRINTS; PR02008; RCMTFAMILY. DR PRINTS; PR02011; RCMTNCL1. DR SUPFAM; SSF53335; SSF53335; 1. DR PROSITE; PS51686; SAM_MT_RSMB_NOP; 1. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Cell cycle; Cell division; Cytoplasm; KW Cytoskeleton; Differentiation; Direct protein sequencing; Disease mutation; KW Isopeptide bond; Mental retardation; Methyltransferase; Mitochondrion; KW Mitosis; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; KW RNA-binding; S-adenosyl-L-methionine; Secreted; Spermatogenesis; KW Transferase; tRNA processing; tRNA-binding; Ubl conjugation. FT CHAIN 1..767 FT /note="RNA cytosine C(5)-methyltransferase NSUN2" FT /id="PRO_0000289223" FT REGION 184..190 FT /note="S-adenosyl-L-methionine binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01023" FT ACT_SITE 321 FT /note="Nucleophile" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01023, FT ECO:0000305|PubMed:28418038, ECO:0000305|PubMed:31358969" FT BINDING 215 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01023" FT BINDING 242 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01023" FT BINDING 268 FT /note="S-adenosyl-L-methionine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01023" FT MOD_RES 139 FT /note="Phosphoserine; by AURKB" FT /evidence="ECO:0000269|PubMed:17215513" FT MOD_RES 456 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:20068231, ECO:0000244|PubMed:23186163, FT ECO:0000244|PubMed:24275569" FT MOD_RES 473 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:21406692" FT MOD_RES 586 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q1HFZ0" FT MOD_RES 586 FT /note="N6-malonyllysine; alternate" FT /evidence="ECO:0000269|PubMed:21908771" FT MOD_RES 593 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692, ECO:0000244|PubMed:23186163" FT MOD_RES 718 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q1HFZ0" FT MOD_RES 724 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q1HFZ0" FT MOD_RES 743 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:16964243, FT ECO:0000244|PubMed:17081983, ECO:0000244|PubMed:18220336, FT ECO:0000244|PubMed:18669648, ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, ECO:0000244|PubMed:23186163, FT ECO:0000244|PubMed:24275569" FT MOD_RES 751 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:16964243, FT ECO:0000244|PubMed:17081983, ECO:0000244|PubMed:18220336, FT ECO:0000244|PubMed:18669648, ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:23186163, ECO:0000244|PubMed:24275569" FT CROSSLNK 46 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000244|PubMed:28112733" FT CROSSLNK 464 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000244|PubMed:28112733" FT CROSSLNK 470 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000244|PubMed:28112733" FT CROSSLNK 511 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000244|PubMed:28112733" FT CROSSLNK 516 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000244|PubMed:28112733" FT CROSSLNK 586 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000244|PubMed:28112733" FT CROSSLNK 640 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000244|PubMed:25218447" FT CROSSLNK 654 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000244|PubMed:28112733" FT CROSSLNK 660 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000244|PubMed:28112733" FT VAR_SEQ 1..236 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_053598" FT VAR_SEQ 85..120 FT /note="SHAKEILHCLKNKYFKELEDLEVDGQKVEVPQPLSW -> R (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_042621" FT VARIANT 627 FT /note="V -> I (in dbSNP:rs2303708)" FT /id="VAR_032604" FT VARIANT 679 FT /note="G -> R (in MRT5; impairs proper intracellular FT localization; dbSNP:rs587776908)" FT /evidence="ECO:0000269|PubMed:22541562" FT /id="VAR_068530" FT MUTAGEN 139 FT /note="S->A: Induces a constitutive association with NPM1." FT /evidence="ECO:0000269|PubMed:17215513" FT MUTAGEN 139 FT /note="S->E: Mimicks constitutive phosphorylation and FT abolishes methyltransferase activity." FT /evidence="ECO:0000269|PubMed:17215513" FT MUTAGEN 190 FT /note="K->M: Loss of RNA methyltransferase activity." FT /evidence="ECO:0000269|PubMed:31186410, FT ECO:0000269|PubMed:31199786" FT MUTAGEN 271 FT /note="C->A: Abolished mRNA methyltransferase activity; FT when associated with A-321." FT /evidence="ECO:0000269|PubMed:28418038, FT ECO:0000269|PubMed:31358969" FT MUTAGEN 321 FT /note="C->A: Abolished mRNA methyltransferase activity; FT when associated with A-271." FT /evidence="ECO:0000269|PubMed:28418038, FT ECO:0000269|PubMed:31358969" FT CONFLICT 316 FT /note="M -> V (in Ref. 2; BAA91075)" FT /evidence="ECO:0000305" FT CONFLICT 327 FT /note="E -> G (in Ref. 2; BAF83833)" FT /evidence="ECO:0000305" FT CONFLICT 484 FT /note="I -> V (in Ref. 2; BAG51521)" FT /evidence="ECO:0000305" FT CONFLICT 594 FT /note="G -> D (in Ref. 2; BAB14762)" FT /evidence="ECO:0000305" FT CONFLICT 605 FT /note="Q -> R (in Ref. 1; BAF34150)" FT /evidence="ECO:0000305" SQ SEQUENCE 767 AA; 86471 MW; FE4B34309978A8D2 CRC64; MGRRSRGRRL QQQQRPEDAE DGAEGGGKRG EAGWEGGYPE IVKENKLFEH YYQELKIVPE GEWGQFMDAL REPLPATLRI TGYKSHAKEI LHCLKNKYFK ELEDLEVDGQ KVEVPQPLSW YPEELAWHTN LSRKILRKSP HLEKFHQFLV SETESGNISR QEAVSMIPPL LLNVRPHHKI LDMCAAPGSK TTQLIEMLHA DMNVPFPEGF VIANDVDNKR CYLLVHQAKR LSSPCIMVVN HDASSIPRLQ IDVDGRKEIL FYDRILCDVP CSGDGTMRKN IDVWKKWTTL NSLQLHGLQL RIATRGAEQL AEGGRMVYST CSLNPIEDEA VIASLLEKSE GALELADVSN ELPGLKWMPG ITQWKVMTKD GQWFTDWDAV PHSRHTQIRP TMFPPKDPEK LQAMHLERCL RILPHHQNTG GFFVAVLVKK SSMPWNKRQP KLQGKSAETR ESTQLSPADL TEGKPTDPSK LESPSFTGTG DTEIAHATED LENNGSKKDG VCGPPPSKKM KLFGFKEDPF VFIPEDDPLF PPIEKFYALD PSFPRMNLLT RTTEGKKRQL YMVSKELRNV LLNNSEKMKV INTGIKVWCR NNSGEEFDCA FRLAQEGIYT LYPFINSRII TVSMEDVKIL LTQENPFFRK LSSETYSQAK DLAKGSIVLK YEPDSANPDA LQCPIVLCGW RGKASIRTFV PKNERLHYLR MMGLEVLGEK KKEGVILTNE SAASTGQPDN DVTEGQRAGE PNSPDAEEAN SPDVTAGCDP AGVHPPR //