NSUN2_MOUSE
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 03-AUG-2022, entry version 131.
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},
GN Misu {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, Pancreas,
RC 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};
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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; 62.
DR IntAct; Q1HFZ0; 2.
DR MINT; Q1HFZ0; -.
DR STRING; 10090.ENSMUSP00000105321; -.
DR iPTMnet; Q1HFZ0; -.
DR PhosphoSitePlus; Q1HFZ0; -.
DR SwissPalm; Q1HFZ0; -.
DR EPD; Q1HFZ0; -.
DR jPOST; Q1HFZ0; -.
DR MaxQB; Q1HFZ0; -.
DR PaxDb; Q1HFZ0; -.
DR PeptideAtlas; Q1HFZ0; -.
DR PRIDE; Q1HFZ0; -.
DR ProteomicsDB; 293756; -. [Q1HFZ0-1]
DR ProteomicsDB; 293757; -. [Q1HFZ0-2]
DR Antibodypedia; 22399; 188 antibodies from 27 providers.
DR DNASU; 28114; -.
DR Ensembl; ENSMUST00000022087; ENSMUSP00000022087; ENSMUSG00000021595. [Q1HFZ0-2]
DR Ensembl; ENSMUST00000109699; ENSMUSP00000105321; ENSMUSG00000021595. [Q1HFZ0-1]
DR GeneID; 28114; -.
DR KEGG; mmu:28114; -.
DR UCSC; uc007rcm.3; mouse. [Q1HFZ0-1]
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; 911098at2759; -.
DR PhylomeDB; Q1HFZ0; -.
DR TreeFam; TF300702; -.
DR BRENDA; 2.1.1.37; 3474.
DR BioGRID-ORCS; 28114; 3 hits in 75 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 282 other tissues.
DR ExpressionAtlas; Q1HFZ0; baseline and differential.
DR Genevisible; Q1HFZ0; MM.
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:0008168; F:methyltransferase activity; IBA:GO_Central.
DR GO; GO:0062152; F:mRNA (cytidine-5-)-methyltransferase activity; IDA: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; 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:0001510; P:RNA methylation; IBA:GO_Central.
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; -; 1.
DR InterPro; IPR001678; MeTrfase_RsmB/NOP2.
DR InterPro; IPR023267; RCMT.
DR InterPro; IPR023270; RCMT_NCL1.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR22808; PTHR22808; 1.
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; 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
