ID NSUN2_MOUSE Reviewed; 757 AA. AC Q1HFZ0; A0PJD6; Q3U972; Q8BPG9; Q8CDF9; Q91YX9; DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 29-MAY-2007, sequence version 2. DT 27-MAR-2024, entry version 140. DE RecName: Full=RNA cytosine C(5)-methyltransferase NSUN2 {ECO:0000305}; DE EC=2.1.1.- {ECO:0000269|PubMed:22885326, ECO:0000269|PubMed:23871666, ECO:0000269|PubMed:31276587, ECO:0000269|PubMed:31287866}; DE AltName: Full=Myc-induced SUN domain-containing protein {ECO:0000303|PubMed:16713953}; DE Short=Misu {ECO:0000303|PubMed:16713953}; DE AltName: Full=NOL1/NOP2/Sun domain family member 2 {ECO:0000303|PubMed:16713953}; DE AltName: Full=mRNA cytosine C(5)-methyltransferase {ECO:0000305}; DE EC=2.1.1.- {ECO:0000269|PubMed:23871666}; DE AltName: Full=tRNA cytosine C(5)-methyltransferase {ECO:0000305}; DE EC=2.1.1.- {ECO:0000269|PubMed:22885326, ECO:0000269|PubMed:23871666, ECO:0000269|PubMed:31276587, ECO:0000269|PubMed:31287866}; DE EC=2.1.1.203 {ECO:0000269|PubMed:22885326}; GN Name=Nsun2 {ECO:0000303|PubMed:16713953, ECO:0000312|MGI:MGI:107252}; GN Synonyms=D13Wsu123e {ECO:0000312|MGI:MGI:107252}, Misu GN {ECO:0000303|PubMed:16713953}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, RP TISSUE SPECIFICITY, AND INDUCTION. RX PubMed=16713953; DOI=10.1016/j.cub.2006.04.027; RA Frye M., Watt F.M.; RT "The RNA methyltransferase Misu (NSun2) mediates Myc-induced proliferation RT and is upregulated in tumors."; RL Curr. Biol. 16:971-981(2006). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Testis; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=Czech II, and FVB/N; TISSUE=Mammary tumor; 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 [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-723, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic brain; RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200; RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.; RT "Phosphoproteomic analysis of the developing mouse brain."; RL Mol. Cell. Proteomics 3:1093-1101(2004). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-723, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [7] 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 [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23; THR-717 AND SER-723, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [9] RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION RP PHENOTYPE. RX PubMed=22144916; DOI=10.1371/journal.pgen.1002403; RA Blanco S., Kurowski A., Nichols J., Watt F.M., Benitah S.A., Frye M.; RT "The RNA-methyltransferase Misu (NSun2) poises epidermal stem cells to RT differentiate."; RL PLoS Genet. 7:E1002403-E1002403(2011). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE. RX PubMed=22885326; DOI=10.1038/nsmb.2357; RA Tuorto F., Liebers R., Musch T., Schaefer M., Hofmann S., Kellner S., RA Frye M., Helm M., Stoecklin G., Lyko F.; RT "RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and RT protein synthesis."; RL Nat. Struct. Mol. Biol. 19:900-905(2012). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-271. 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 [12] RP DISRUPTION PHENOTYPE, AND SUBCELLULAR LOCATION. RX PubMed=23401851; DOI=10.1128/mcb.01523-12; RA Hussain S., Tuorto F., Menon S., Blanco S., Cox C., Flores J.V., Watt S., RA Kudo N.R., Lyko F., Frye M.; RT "The mouse cytosine-5 RNA methyltransferase NSun2 is a component of the RT chromatoid body and required for testis differentiation."; RL Mol. Cell. Biol. 33:1561-1570(2013). RN [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-585, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001; RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.; RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic RT pathways."; RL Mol. Cell 50:919-930(2013). RN [14] RP SUBCELLULAR LOCATION. RX PubMed=28341602; DOI=10.1016/j.bbapap.2017.03.010; RA Kossinova O.A., Gopanenko A.V., Tamkovich S.N., Krasheninina O.A., RA Tupikin A.E., Kiseleva E., Yanshina D.D., Malygin A.A., Ven'yaminova A.G., RA Kabilov M.R., Karpova G.G.; RT "Cytosolic YB-1 and NSUN2 are the only proteins recognizing specific motifs RT present in mRNAs enriched in exosomes."; RL Biochim. Biophys. Acta 1865:664-673(2017). RN [15] RP FUNCTION, AND CATALYTIC ACTIVITY. 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. 47:8720-8733(2019). RN [16] RP FUNCTION, AND CATALYTIC ACTIVITY. 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. 47:8734-8745(2019). RN [17] RP FUNCTION. 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). 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:22144916, PubMed:23871666, CC PubMed:31199786). Involved in various processes, such as epidermal stem CC cell differentiation, testis differentiation and maternal to zygotic CC transition during early development: acts by increasing protein CC synthesis; cytosine C(5)-methylation promoting tRNA stability and CC preventing mRNA decay (PubMed:22144916, PubMed:22885326, CC PubMed:23401851, PubMed:31199786). Methylates cytosine to 5- CC methylcytosine (m5C) at positions 34 and 48 of intron-containing CC tRNA(Leu)(CAA) precursors, and at positions 48, 49 and 50 of CC tRNA(Gly)(GCC) precursors (PubMed:22885326, PubMed:23871666, 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, CC PubMed:31287866). Catalyzes cytosine C(5)-methylation of mRNAs, leading CC to stabilize them and prevent mRNA decay: mRNA stabilization involves CC YBX1 that specifically recognizes and binds m5C-modified transcripts CC (By similarity). Cytosine C(5)-methylation of mRNAs also regulates mRNA CC export: methylated transcripts are specifically recognized by CC THOC4/ALYREF, which mediates mRNA nucleo-cytoplasmic shuttling (By CC similarity). Also mediates cytosine C(5)-methylation of non-coding CC RNAs, such as vault RNAs (vtRNAs), promoting their processing into CC regulatory small RNAs (PubMed:23871666). Cytosine C(5)-methylation of CC vtRNA VTRNA1.1 promotes its processing into small-vault RNA4 (svRNA4) CC and regulates epidermal differentiation (By similarity). May act CC downstream of Myc to regulate epidermal cell growth and proliferation CC (PubMed:16713953). Required for proper spindle assembly and chromosome CC segregation, independently of its methyltransferase activity CC (PubMed:19596847). {ECO:0000250|UniProtKB:Q08J23, CC ECO:0000269|PubMed:16713953, ECO:0000269|PubMed:19596847, CC ECO:0000269|PubMed:22144916, ECO:0000269|PubMed:22885326, CC ECO:0000269|PubMed:23401851, ECO:0000269|PubMed:23871666, CC ECO:0000269|PubMed:31199786, ECO:0000269|PubMed:31276587, CC ECO:0000269|PubMed:31287866}. 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:22885326, ECO:0000269|PubMed:23871666, CC ECO:0000269|PubMed:31276587, ECO:0000269|PubMed:31287866}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42949; CC Evidence={ECO:0000269|PubMed:22885326, ECO:0000269|PubMed:23871666, CC ECO:0000269|PubMed:31276587, ECO:0000269|PubMed:31287866}; 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:22885326, ECO:0000269|PubMed:23871666, CC ECO:0000269|PubMed:31276587, ECO:0000269|PubMed:31287866}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42953; CC Evidence={ECO:0000269|PubMed:22885326, ECO:0000269|PubMed:23871666, CC ECO:0000269|PubMed:31276587, ECO:0000269|PubMed:31287866}; 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:22885326, ECO:0000269|PubMed:23871666, CC ECO:0000269|PubMed:31276587, ECO:0000269|PubMed:31287866}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61489; CC Evidence={ECO:0000269|PubMed:22885326, ECO:0000269|PubMed:23871666, CC ECO:0000269|PubMed:31276587, ECO:0000269|PubMed:31287866}; 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:22885326}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42941; CC Evidence={ECO:0000269|PubMed:22885326}; 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:23871666}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61465; CC Evidence={ECO:0000269|PubMed:23871666}; CC -!- ACTIVITY REGULATION: Inhibited by magnesium ions. CC {ECO:0000250|UniProtKB:Q08J23}. CC -!- SUBUNIT: Interacts with NPM1 and NCL during interphase; interaction is CC disrupted following phosphorylation at Ser-139. CC {ECO:0000250|UniProtKB:Q08J23}. CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:16713953, CC ECO:0000269|PubMed:19596847}. Cytoplasm {ECO:0000250|UniProtKB:Q08J23}. CC Mitochondrion {ECO:0000250|UniProtKB:Q08J23}. Cytoplasm, cytoskeleton, CC spindle {ECO:0000269|PubMed:19596847}. Secreted, extracellular exosome CC {ECO:0000269|PubMed:28341602}. 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 (PubMed:23401851). CC {ECO:0000269|PubMed:19596847, ECO:0000269|PubMed:23401851}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q1HFZ0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q1HFZ0-2; Sequence=VSP_025969; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed at low level CC (PubMed:16713953). Up-regulated in tumors (PubMed:16713953). CC Dynamically expressed during morphogenesis and in adult skin: in adult CC skin, expression is up-regulated in the bulge and hair germ as soon as CC the hair follicle enters its growing phase (anagen) (PubMed:22144916). CC During anagen, expressed at highest level in cells of the hair germ CC that give rise to the hair matrix (PubMed:22144916). CC {ECO:0000269|PubMed:16713953, ECO:0000269|PubMed:22144916}. CC -!- DEVELOPMENTAL STAGE: Detected from 3.5 dpc in the inner cell mass of CC the blastocyst (PubMed:22144916). Expressed throughout the extra- CC embryonic ectoderm, which gives rise to the nervous system and CC epidermis, after implantation and gastrulation (PubMed:22144916). CC Starting from 9.5 dpc, expression becomes more restricted and at 13.5 CC and 14.5 dpc it is enriched in developing whiskers and eyes CC (PubMed:22144916). From 15.5 dpc, when the interfollicular epidermis CC begins to stratify and follicular morphogenesis starts by forming hair CC placodes, highest expression is observed in the suprabasal layer of CC interfollicular epidermis (PubMed:22144916). CC {ECO:0000269|PubMed:22144916}. CC -!- INDUCTION: By Myc (at protein level). {ECO:0000269|PubMed:16713953}. CC -!- PTM: Phosphorylated at Ser-139 by AURKB during mitosis, leading to CC abolish methyltransferase activity and the interaction with NPM1. CC {ECO:0000250|UniProtKB:Q08J23}. CC -!- DISRUPTION PHENOTYPE: Mice are viable but show male sterility CC (PubMed:22144916, PubMed:23401851). Mice display reduced body weight CC and partial alopecia; alopecia is caused by impaired stem cell CC differentiation in the epidermis, leading to a delay in initiation of CC anagen (PubMed:22144916). Mice lacking both Nsun2 and Trdmt1 display a CC complete loss of cytosine-C5 tRNA methylation, leading to development CC defects and impaired cellular differentiation causing lethality before CC P3 (PubMed:22885326). Male sterility is caused by impaired germ cell CC differentiation in the testis: meiotic progression of germ cells is CC blocked into the pachytene stage, while spermatogonial and Sertoli CC cells are unaffected (PubMed:23401851). {ECO:0000269|PubMed:22144916, CC ECO:0000269|PubMed:22885326, ECO:0000269|PubMed:23401851}. 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=AAH13625.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAH25549.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=BAC36110.1; Type=Erroneous initiation; 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; DQ490066; ABF29536.1; -; mRNA. DR EMBL; AK030124; BAC26795.1; -; mRNA. DR EMBL; AK075999; BAC36110.1; ALT_INIT; mRNA. DR EMBL; AK150631; BAE29720.1; -; mRNA. DR EMBL; AK151917; BAE30795.1; -; mRNA. DR EMBL; BC013625; AAH13625.1; ALT_INIT; mRNA. DR EMBL; BC025549; AAH25549.1; ALT_SEQ; mRNA. DR CCDS; CCDS36722.2; -. [Q1HFZ0-1] DR RefSeq; NP_663329.3; NM_145354.5. [Q1HFZ0-1] DR AlphaFoldDB; Q1HFZ0; -. DR BioGRID; 205771; 63. DR IntAct; Q1HFZ0; 2. DR MINT; Q1HFZ0; -. DR STRING; 10090.ENSMUSP00000105321; -. DR GlyGen; Q1HFZ0; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q1HFZ0; -. DR MetOSite; Q1HFZ0; -. DR PhosphoSitePlus; Q1HFZ0; -. DR SwissPalm; Q1HFZ0; -. DR EPD; Q1HFZ0; -. DR jPOST; Q1HFZ0; -. DR MaxQB; Q1HFZ0; -. DR PaxDb; 10090-ENSMUSP00000105321; -. DR PeptideAtlas; Q1HFZ0; -. DR ProteomicsDB; 293756; -. [Q1HFZ0-1] DR ProteomicsDB; 293757; -. [Q1HFZ0-2] DR Pumba; Q1HFZ0; -. DR Antibodypedia; 22399; 211 antibodies from 27 providers. DR DNASU; 28114; -. DR Ensembl; ENSMUST00000022087.7; ENSMUSP00000022087.7; ENSMUSG00000021595.19. [Q1HFZ0-2] DR Ensembl; ENSMUST00000109699.11; ENSMUSP00000105321.5; ENSMUSG00000021595.19. [Q1HFZ0-1] DR GeneID; 28114; -. DR KEGG; mmu:28114; -. DR UCSC; uc007rcm.3; mouse. [Q1HFZ0-1] DR AGR; MGI:107252; -. DR CTD; 54888; -. DR MGI; MGI:107252; Nsun2. DR VEuPathDB; HostDB:ENSMUSG00000021595; -. DR eggNOG; KOG2198; Eukaryota. DR GeneTree; ENSGT00940000153665; -. DR HOGENOM; CLU_005316_4_3_1; -. DR InParanoid; Q1HFZ0; -. DR OMA; QLFTEYV; -. DR OrthoDB; 197651at2759; -. DR PhylomeDB; Q1HFZ0; -. DR TreeFam; TF300702; -. DR BRENDA; 2.1.1.37; 3474. DR BioGRID-ORCS; 28114; 3 hits in 80 CRISPR screens. DR ChiTaRS; Nsun2; mouse. DR PRO; PR:Q1HFZ0; -. DR Proteomes; UP000000589; Chromosome 13. DR RNAct; Q1HFZ0; Protein. DR Bgee; ENSMUSG00000021595; Expressed in cranial placode and 286 other cell types or tissues. DR ExpressionAtlas; Q1HFZ0; baseline and differential. DR GO; GO:0033391; C:chromatoid body; IDA:CACAO. DR GO; GO:0005737; C:cytoplasm; ISO:MGI. DR GO; GO:0070062; C:extracellular exosome; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB. DR GO; GO:0005730; C:nucleolus; ISO:MGI. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell. DR GO; GO:0062152; F:mRNA (cytidine-5-)-methyltransferase activity; IDA:UniProtKB. DR GO; GO:0016428; F:tRNA (cytidine-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; IMP:UniProtKB. DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI. DR GO; GO:0033313; P:meiotic cell cycle checkpoint signaling; IMP:CACAO. DR GO; GO:0080009; P:mRNA methylation; IDA:UniProtKB. DR GO; GO:0010793; P:regulation of mRNA export from nucleus; ISS:UniProtKB. DR GO; GO:2000736; P:regulation of stem cell differentiation; IMP:UniProtKB. DR GO; GO:0007286; P:spermatid development; IMP:CACAO. DR GO; GO:0030488; P:tRNA methylation; IDA:UniProtKB. DR GO; GO:0036416; P:tRNA stabilization; IMP:UniProtKB. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR InterPro; IPR049560; MeTrfase_RsmB-F_NOP2_cat. DR InterPro; IPR001678; MeTrfase_RsmB-F_NOP2_dom. DR InterPro; IPR023267; RCMT. DR InterPro; IPR023270; RCMT_NCL1. DR InterPro; IPR029063; SAM-dependent_MTases_sf. DR PANTHER; PTHR22808; NCL1 YEAST -RELATED NOL1/NOP2/FMU SUN DOMAIN-CONTAINING; 1. DR PANTHER; PTHR22808:SF1; RNA CYTOSINE C(5)-METHYLTRANSFERASE NSUN2; 1. DR Pfam; PF01189; Methyltr_RsmB-F; 1. DR PRINTS; PR02008; RCMTFAMILY. DR PRINTS; PR02011; RCMTNCL1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR PROSITE; PS51686; SAM_MT_RSMB_NOP; 1. DR Genevisible; Q1HFZ0; MM. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Cell cycle; Cell division; Cytoplasm; KW Cytoskeleton; Differentiation; Isopeptide bond; Methyltransferase; KW Mitochondrion; Mitosis; Nucleus; Phosphoprotein; Reference proteome; KW RNA-binding; S-adenosyl-L-methionine; Secreted; Spermatogenesis; KW Transferase; tRNA processing; tRNA-binding; Ubl conjugation. FT CHAIN 1..757 FT /note="RNA cytosine C(5)-methyltransferase NSUN2" FT /id="PRO_0000289224" FT REGION 1..35 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 436..504 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 716..757 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 459..487 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 321 FT /note="Nucleophile" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01023" FT BINDING 184..190 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01023" FT BINDING 215 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01023" FT BINDING 242 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01023" FT BINDING 268 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01023" FT MOD_RES 23 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355, FT ECO:0007744|PubMed:21183079" FT MOD_RES 139 FT /note="Phosphoserine; by AURKB" FT /evidence="ECO:0000250|UniProtKB:Q08J23" FT MOD_RES 456 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q08J23" FT MOD_RES 473 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q08J23" FT MOD_RES 585 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 585 FT /note="N6-malonyllysine; alternate" FT /evidence="ECO:0000250" FT MOD_RES 592 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q08J23" FT MOD_RES 717 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 723 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:15345747, FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079" FT CROSSLNK 46 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q08J23" FT CROSSLNK 510 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q08J23" FT CROSSLNK 515 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q08J23" FT CROSSLNK 585 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:Q08J23" FT CROSSLNK 639 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q08J23" FT CROSSLNK 653 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q08J23" FT CROSSLNK 659 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q08J23" FT VAR_SEQ 1..66 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:16141072" FT /id="VSP_025969" FT MUTAGEN 271 FT /note="C->A: Loss of RNA methyltransferase activity." FT /evidence="ECO:0000269|PubMed:23871666" FT CONFLICT 206 FT /note="F -> L (in Ref. 2; BAE30795/BAE29720)" FT /evidence="ECO:0000305" FT CONFLICT 253 FT /note="V -> L (in Ref. 2; BAE30795/BAE29720)" FT /evidence="ECO:0000305" FT CONFLICT 482 FT /note="S -> L (in Ref. 1; ABF29536 and 3; AAH25549)" FT /evidence="ECO:0000305" FT CONFLICT 490 FT /note="N -> I (in Ref. 1; ABF29536)" FT /evidence="ECO:0000305" SQ SEQUENCE 757 AA; 85452 MW; 73B06947DEC50298 CRC64; MGRRARGRRF QQPPQPEGEE DASDGGRKRG QAGWEGGYPE IVKENKLFEH YYQELKIVPE GEWDQFMESL REPLPATLRI TGYKSHAKEI LHCLKNKYFK ELEDLEVDGQ KVEVPQPLSW YPEELAWHTN LSRKILRKSP LLAKFHQFLV SETESGNISR QEAVSMIPPL LLNVEPHHKI LDMCAAPGSK TTQLIEMLHA DMSVPFPEGF VIANDVDNKR CYLLVHQAKR LSSPCIMVVN HDASSIPRLT VDVDGRKEIL FYDRILCDVP CSGDGTMRKN IDVWKKWTTL NSLQLHGLQL RIATRGAEQL AEGGRMVYST CSLNPVEDEA VIAALLEKSE GALELADVSA ELPGLKWMPG VSQWKVMTRD GQWFADWHEV PQGRHTQIRP TMFPPTDLEK LQAMHLERCL RILPHHQNTG GFFVAVLVKK APMPWNKRQP KVQNKSAEAR EPRVSSHVAA TEGNPSDQSE LESQMITGAG DSETAHNTEN TESNEKKDGV CGPPPSKKMK LFGFKEDPFV FIPEDDPLFP PIEKFYALDP SFPRMNLLTR TTEGKKRQLY MVSKELRNVL LNNSEKMKVI NTGIKVWCRN NSGEEFDCAF RLAQEGIYTL YPFINSRIIT VSMEDVKTLL TQENPFFRKL SSEAYSQVKD LAKGSVVLKY EPDSANPDTL QCPIVLCGWR GKASIRTFVP KNERLHYLRM MGLEVLGEKK KEGVILTNEN AASPEQPGDE DAKQTAQDPC VPDSVPGCDA AAAEPSR //