ID NSD2_MOUSE Reviewed; 1365 AA. AC Q8BVE8; B3VCH6; Q6ZPY1; Q7TSF5; Q811F0; DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 31-OCT-2006, sequence version 2. DT 27-MAR-2024, entry version 171. DE RecName: Full=Histone-lysine N-methyltransferase NSD2; DE EC=2.1.1.357 {ECO:0000269|PubMed:19483677, ECO:0000269|PubMed:31636135, ECO:0000269|PubMed:32862441}; DE AltName: Full=Multiple myeloma SET domain-containing protein; DE Short=MMSET; DE AltName: Full=Nuclear SET domain-containing protein 2; DE AltName: Full=Wolf-Hirschhorn syndrome candidate 1 protein homolog; GN Name=Nsd2; Synonyms=Kiaa1090, Whsc1; 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 RE-IIBP), FUNCTION (ISOFORM RE-IIBP), RP AND MUTAGENESIS OF ARG-1138 AND CYS-1144. RX PubMed=18172012; DOI=10.1128/mcb.02130-07; RA Kim J.Y., Kee H.J., Choe N.W., Kim S.M., Eom G.H., Baek H.J., Kook H., RA Kook H., Seo S.B.; RT "Multiple-myeloma-related WHSC1/MMSET isoform RE-IIBP is a histone RT methyltransferase with transcriptional repression activity."; RL Mol. Cell. Biol. 28:2023-2034(2008). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Embryonic tail; RX PubMed=14621295; DOI=10.1093/dnares/10.4.167; RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., RA Saga Y., Nagase T., Ohara O., Koga H.; RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III. RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs RT identified by screening of terminal sequences of cDNA clones randomly RT sampled from size-fractionated libraries."; RL DNA Res. 10:167-180(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 446-1365 (ISOFORM 1). RC STRAIN=C57BL/6J; TISSUE=Adrenal gland; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 516-1365 (ISOFORM 2). RC STRAIN=FVB/N; TISSUE=Limb, and 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 [6] RP DEVELOPMENTAL STAGE. RX PubMed=9618163; DOI=10.1093/hmg/7.7.1071; RA Stec I., Wright T.J., van Ommen G.-J.B., de Boer P.A., van Haeringen A., RA Moorman A.F.M., Altherr M.R., den Dunnen J.T.; RT "WHSC1, a 90 kb SET domain-containing gene, expressed in early development RT and homologous to a Drosophila dysmorphy gene maps in the Wolf-Hirschhorn RT syndrome critical region and is fused to IgH in t(4;14) multiple myeloma."; RL Hum. Mol. Genet. 7:1071-1082(1998). RN [7] RP ERRATUM OF PUBMED:9618163. RA Stec I., Wright T.J., van Ommen G.-J.B., de Boer P.A., van Haeringen A., RA Moorman A.F.M., Altherr M.R., den Dunnen J.T.; RL Hum. Mol. Genet. 7:1527-1527(1998). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH SALL1; SALL4; NANOG; HDAC1; RP NKX2-5 AND OGT, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISRUPTION RP PHENOTYPE, AND MUTAGENESIS OF HIS-1142. RX PubMed=19483677; DOI=10.1038/nature08086; RA Nimura K., Ura K., Shiratori H., Ikawa M., Okabe M., Schwartz R.J., RA Kaneda Y.; RT "A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf- RT Hirschhorn syndrome."; RL Nature 460:287-291(2009). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-110 AND SER-121, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Lung, 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 [10] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF PHE-1117. RX PubMed=23241889; DOI=10.4049/jimmunol.1201811; RA Pei H., Wu X., Liu T., Yu K., Jelinek D.F., Lou Z.; RT "The histone methyltransferase MMSET regulates class switch RT recombination."; RL J. Immunol. 190:756-763(2013). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND INDUCTION. RX PubMed=32862441; DOI=10.1002/1873-3468.13903; RA Dobenecker M.W., Marcello J., Becker A., Rudensky E., Bhanu N.V., RA Carrol T., Garcia B.A., Prinjha R., Yurchenko V., Tarakhovsky A.; RT "The catalytic domain of the histone methyltransferase NSD2/MMSET is RT required for the generation of B1 cells in mice."; RL FEBS Lett. 594:3324-3337(2020). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, INDUCTION, AND DISRUPTION PHENOTYPE. RX PubMed=31636135; DOI=10.1084/jem.20190832; RA Long X., Zhang L., Zhang Y., Min M., Lin B., Chen J., Ma X., Zhai S., RA Cai Z., Liu Y., Lu Y., Che N., Tan W., Qin J., Wang X.; RT "Histone methyltransferase Nsd2 is required for follicular helper T cell RT differentiation."; RL J. Exp. Med. 217:0-0(2020). CC -!- FUNCTION: Histone methyltransferase which specifically dimethylates CC nucleosomal histone H3 at 'Lys-36' (H3K36me2) (PubMed:19483677, CC PubMed:32862441, PubMed:31636135). Also monomethylates nucleosomal CC histone H3 at 'Lys-36' (H3K36me) in vitro (PubMed:19483677). Does not CC trimethylate nucleosomal histone H3 at 'Lys-36' (H3K36me3) (By CC similarity). However, specifically trimethylates histone H3 at 'Lys-36' CC (H3K36me3) at euchromatic regions in embryonic stem (ES) cells CC (PubMed:19483677). By methylating histone H3 at 'Lys-36', involved in CC the regulation of gene transcription during various biological CC processes (PubMed:19483677, PubMed:31636135, PubMed:32862441, CC PubMed:23241889). In ES cells, associates with developmental CC transcription factors such as SALL1 and represses inappropriate gene CC transcription mediated by histone deacetylation (PubMed:19483677). CC During heart development, associates with transcription factor NKX2-5 CC to repress transcription of NKX2-5 target genes (PubMed:19483677). CC Plays an essential role in adipogenesis, by regulating expression of CC genes involved in pre-adipocyte differentiation (By similarity). During CC T-cell receptor (TCR) and CD28-mediated T-cell activation, promotes the CC transcription of transcription factor BCL6 which is required for CC follicular helper T (Tfh) cell differentiation (PubMed:31636135). CC During B-cell development, required for the generation of the B1 CC lineage (PubMed:32862441). During B2 cell activation, may contribute to CC the control of isotype class switch recombination (CRS), splenic CC germinal center formation, and the humoral immune response CC (PubMed:32862441). Plays a role in class switch recombination of the CC immunoglobulin heavy chain (IgH) locus during B-cell activation CC (PubMed:23241889). By regulating the methylation of histone H3 at 'Lys- CC 36' and histone H4 at 'Lys-20' at the IgH locus, involved in TP53BP1 CC recruitment to the IgH switch region and promotes the transcription of CC IgA (PubMed:23241889). {ECO:0000250|UniProtKB:O96028, CC ECO:0000269|PubMed:19483677, ECO:0000269|PubMed:23241889, CC ECO:0000269|PubMed:31636135, ECO:0000269|PubMed:32862441}. CC -!- FUNCTION: [Isoform RE-IIBP]: Histone methyltransferase which CC specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2) CC (By similarity). Mono-, di- and tri-methylates histone H3 at 'Lys-27' CC (H3K27me, H3K27me2, H3K27me3) (PubMed:18172012). Methylation of histone CC H3 at 'Lys-27' is controversial (By similarity). May act as a CC transcription regulator that binds DNA and suppresses IL5 transcription CC through HDAC recruitment (PubMed:18172012). CC {ECO:0000250|UniProtKB:O96028, ECO:0000269|PubMed:18172012}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl(36)-[histone H3] + S-adenosyl-L-methionine = H(+) + CC N(6)-methyl-L-lysyl(36)-[histone H3] + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:60312, Rhea:RHEA-COMP:9785, Rhea:RHEA-COMP:9786, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; CC Evidence={ECO:0000269|PubMed:19483677}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl(36)-[histone H3] + 2 S-adenosyl-L-methionine = 2 H(+) CC + N(6),N(6)-dimethyl-L-lysyl(36)-[histone H3] + 2 S-adenosyl-L- CC homocysteine; Xref=Rhea:RHEA:60308, Rhea:RHEA-COMP:9785, Rhea:RHEA- CC COMP:9787, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61976; EC=2.1.1.357; CC Evidence={ECO:0000269|PubMed:19483677, ECO:0000269|PubMed:31636135, CC ECO:0000269|PubMed:32862441}; CC -!- SUBUNIT: Interacts with HDAC1 (PubMed:19483677). Interacts (via PHD- CC type zinc fingers 1, 2 and 3) with SALL1 (PubMed:19483677). Interacts CC (via PHD-type 1, 2 and 3) with SALL4 (PubMed:19483677). Interacts with CC NANOG (PubMed:19483677). Interacts with OGT (PubMed:19483677). CC Interacts (via HMG box) with NKX2-5 (PubMed:19483677). CC {ECO:0000269|PubMed:19483677}. CC -!- INTERACTION: CC Q8BVE8-2; P42582: Nkx2-5; NbExp=2; IntAct=EBI-11518042, EBI-297021; CC Q8BVE8-2; Q8BX22: Sall4; NbExp=3; IntAct=EBI-11518042, EBI-2312582; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00267, CC ECO:0000269|PubMed:19483677}. Chromosome {ECO:0000269|PubMed:19483677, CC ECO:0000269|PubMed:23241889}. Note=In embryonic stem (ES) cells, CC localizes to small foci, probably corresponding to euchromatin CC (PubMed:19483677). In B-cells, localizes to Ig heavy chain switch CC region during class switch recombination (PubMed:23241889). CC {ECO:0000269|PubMed:19483677, ECO:0000269|PubMed:23241889}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q8BVE8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8BVE8-2; Sequence=VSP_021426; CC Name=3; CC IsoId=Q8BVE8-3; Sequence=VSP_021424, VSP_021425, VSP_021426; CC Name=RE-IIBP {ECO:0000303|PubMed:18172012}; CC IsoId=Q8BVE8-4; Sequence=VSP_044420; CC -!- TISSUE SPECIFICITY: During B-cell development, expressed in early B2 CC cell progenitors (pre- and pro-B cells) with a decrease in expression CC at later stages. {ECO:0000269|PubMed:32862441}. CC -!- DEVELOPMENTAL STAGE: Ubiquitously expressed in early development CC (PubMed:9618163). Highly expressed in neuroepithelium at 10.5 dpc, and CC in the forebrain, midbrain, frontal facial region, jaw, heart but not CC in the endocardial cushion, and cartilage primordial at 14.5 dpc CC (PubMed:19483677). {ECO:0000269|PubMed:19483677, CC ECO:0000269|PubMed:9618163}. CC -!- INDUCTION: Induced in CD4(+) T-cell in response to T-cell receptor CC (TCR) and CD28 stimulation (at protein level) (PubMed:31636135). CC Induced in B2-cells by IgM antibodies or lipopolysaccharide (LPS) CC stimulation (PubMed:32862441). {ECO:0000269|PubMed:31636135, CC ECO:0000269|PubMed:32862441}. CC -!- DISRUPTION PHENOTYPE: Offspring number is low at birth CC (PubMed:19483677). After birth, pups have growth retardation and die CC within 10 days (PubMed:19483677). At 15.5 dpc, levels of trimethylated CC 'Lys-36' on histone H3 are reduced (PubMed:19483677). At 18.5 dpc, CC embryos are smaller with midline fusion defects due to a lack of CC ossification centers and some have cleft palates (PubMed:19483677). CC They also have heart defects including atrial and ventricular septal CC defects (PubMed:19483677). Conditional knockout in CD4(+) T-cells, CC reduces dimethylation of histone H3 at 'Lys-36' at the Bcl6 gene locus CC in response to T-cell activation which results in impaired Bcl6 CC expresseion (PubMed:31636135). Following immunization with ovalbumin CC antigen or sheep red blood cells, or infection with LCMV virus, CC follicular helper T (Tfh) cell differentiation and germinal center B CC cell response are reduced (PubMed:31636135). Also, following infection CC with LCMV virus, clearance of the virus is delayed (PubMed:31636135). CC No defect in T-cell development (PubMed:31636135). CC {ECO:0000269|PubMed:19483677, ECO:0000269|PubMed:31636135}. CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase CC superfamily. Histone-lysine methyltransferase family. SET2 subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00190}. CC -!- CAUTION: Depending on the experimental set up and substrate used, NSD2 CC has been shown to mono-, di- or tri-methylate 'Lys-27', 'Lys-36' or CC 'Lys-79' of histone H3 and 'Lys-20' or 'Lys-44' of histone H4 (By CC similarity). However, dimethylation of nucleosomal histone H3 at 'Lys- CC 36' (H3K36me2) is likely to be the physiological reaction catalyzed by CC NSD2 (By similarity). {ECO:0000250|UniProtKB:O96028}. CC -!- SEQUENCE CAUTION: CC Sequence=ACE75882.1; Type=Miscellaneous discrepancy; Note=Incorrectly indicated as originating from human.; Evidence={ECO:0000305}; CC Sequence=BAC37342.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAC98097.1; 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; EU733655; ACE75882.1; ALT_SEQ; mRNA. DR EMBL; AK129287; BAC98097.1; ALT_INIT; mRNA. DR EMBL; AC163329; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AK078622; BAC37342.1; ALT_FRAME; mRNA. DR EMBL; BC046473; AAH46473.1; -; mRNA. DR EMBL; BC053454; AAH53454.1; -; mRNA. DR CCDS; CCDS51467.1; -. [Q8BVE8-2] DR CCDS; CCDS51468.1; -. [Q8BVE8-1] DR RefSeq; NP_001074571.2; NM_001081102.2. [Q8BVE8-2] DR RefSeq; NP_780440.2; NM_175231.2. [Q8BVE8-1] DR RefSeq; XP_006503721.1; XM_006503658.3. [Q8BVE8-2] DR RefSeq; XP_006503722.1; XM_006503659.3. [Q8BVE8-2] DR RefSeq; XP_006503723.1; XM_006503660.3. [Q8BVE8-1] DR RefSeq; XP_017176079.1; XM_017320590.1. DR AlphaFoldDB; Q8BVE8; -. DR SMR; Q8BVE8; -. DR BioGRID; 223605; 14. DR DIP; DIP-60452N; -. DR IntAct; Q8BVE8; 14. DR MINT; Q8BVE8; -. DR STRING; 10090.ENSMUSP00000075210; -. DR GlyGen; Q8BVE8; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8BVE8; -. DR PhosphoSitePlus; Q8BVE8; -. DR SwissPalm; Q8BVE8; -. DR EPD; Q8BVE8; -. DR jPOST; Q8BVE8; -. DR MaxQB; Q8BVE8; -. DR PaxDb; 10090-ENSMUSP00000058940; -. DR PeptideAtlas; Q8BVE8; -. DR ProteomicsDB; 293976; -. [Q8BVE8-1] DR ProteomicsDB; 293977; -. [Q8BVE8-2] DR ProteomicsDB; 293978; -. [Q8BVE8-3] DR ProteomicsDB; 293979; -. [Q8BVE8-4] DR Pumba; Q8BVE8; -. DR ABCD; Q8BVE8; 1 sequenced antibody. DR Antibodypedia; 8608; 212 antibodies from 31 providers. DR Ensembl; ENSMUST00000058096.14; ENSMUSP00000058940.8; ENSMUSG00000057406.17. [Q8BVE8-1] DR Ensembl; ENSMUST00000066854.14; ENSMUSP00000067205.8; ENSMUSG00000057406.17. [Q8BVE8-2] DR Ensembl; ENSMUST00000075812.11; ENSMUSP00000075210.5; ENSMUSG00000057406.17. [Q8BVE8-2] DR GeneID; 107823; -. DR KEGG; mmu:107823; -. DR UCSC; uc008xbm.2; mouse. [Q8BVE8-1] DR UCSC; uc012duw.1; mouse. [Q8BVE8-2] DR AGR; MGI:1276574; -. DR CTD; 7468; -. DR MGI; MGI:1276574; Nsd2. DR VEuPathDB; HostDB:ENSMUSG00000057406; -. DR eggNOG; KOG1081; Eukaryota. DR GeneTree; ENSGT00940000157429; -. DR HOGENOM; CLU_004494_2_1_1; -. DR InParanoid; Q8BVE8; -. DR OMA; SEHEFGV; -. DR OrthoDB; 950362at2759; -. DR PhylomeDB; Q8BVE8; -. DR TreeFam; TF329088; -. DR BRENDA; 2.1.1.357; 3474. DR BRENDA; 2.1.1.359; 3474. DR Reactome; R-MMU-3214841; PKMTs methylate histone lysines. DR Reactome; R-MMU-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks. DR Reactome; R-MMU-5693571; Nonhomologous End-Joining (NHEJ). DR Reactome; R-MMU-5693607; Processing of DNA double-strand break ends. DR Reactome; R-MMU-69473; G2/M DNA damage checkpoint. DR BioGRID-ORCS; 107823; 11 hits in 118 CRISPR screens. DR ChiTaRS; Whsc1; mouse. DR PRO; PR:Q8BVE8; -. DR Proteomes; UP000000589; Chromosome 5. DR RNAct; Q8BVE8; Protein. DR Bgee; ENSMUSG00000057406; Expressed in manus and 249 other cell types or tissues. DR ExpressionAtlas; Q8BVE8; baseline and differential. DR GO; GO:0000785; C:chromatin; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0003682; F:chromatin binding; IDA:MGI. DR GO; GO:0140954; F:histone H3K36 dimethyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0046975; F:histone H3K36 methyltransferase activity; ISS:UniProtKB. DR GO; GO:0140955; F:histone H3K36 trimethyltransferase activity; IDA:MGI. DR GO; GO:0042054; F:histone methyltransferase activity; IDA:MGI. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI. DR GO; GO:0003289; P:atrial septum primum morphogenesis; IMP:MGI. DR GO; GO:0003290; P:atrial septum secundum morphogenesis; IMP:MGI. DR GO; GO:0060348; P:bone development; IMP:MGI. DR GO; GO:0003149; P:membranous septum morphogenesis; IMP:MGI. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:MGI. DR GO; GO:0048298; P:positive regulation of isotype switching to IgA isotypes; IMP:MGI. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IMP:MGI. DR GO; GO:2001032; P:regulation of double-strand break repair via nonhomologous end joining; IMP:MGI. DR GO; GO:0070201; P:regulation of establishment of protein localization; IMP:MGI. DR CDD; cd21991; HMG-box_NSD2; 1. DR CDD; cd15648; PHD1_NSD1_2; 1. DR CDD; cd15651; PHD2_NSD2; 1. DR CDD; cd15654; PHD3_NSD2; 1. DR CDD; cd15660; PHD5_NSD2; 1. DR CDD; cd20162; PWWP_NSD2_rpt1; 1. DR CDD; cd20165; PWWP_NSD2_rpt2; 1. DR CDD; cd19211; SET_NSD2; 1. DR Gene3D; 2.30.30.140; -; 2. DR Gene3D; 1.10.30.10; High mobility group box domain; 1. DR Gene3D; 2.170.270.10; SET domain; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 4. DR InterPro; IPR006560; AWS_dom. DR InterPro; IPR041306; C5HCH. DR InterPro; IPR047443; HMG-box_NSD2. DR InterPro; IPR009071; HMG_box_dom. DR InterPro; IPR036910; HMG_box_dom_sf. DR InterPro; IPR047426; PHD1_NSD1_2. DR InterPro; IPR047439; PHD2_NSD2. DR InterPro; IPR047441; PHD3_NSD2. DR InterPro; IPR047442; PHD5_NSD2. DR InterPro; IPR003616; Post-SET_dom. DR InterPro; IPR000313; PWWP_dom. DR InterPro; IPR047434; PWWP_NSD2_rpt1. DR InterPro; IPR047435; PWWP_NSD2_rpt2. DR InterPro; IPR001214; SET_dom. DR InterPro; IPR046341; SET_dom_sf. DR InterPro; IPR047437; SET_NSD2. DR InterPro; IPR019786; Zinc_finger_PHD-type_CS. DR InterPro; IPR011011; Znf_FYVE_PHD. DR InterPro; IPR001965; Znf_PHD. DR InterPro; IPR019787; Znf_PHD-finger. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR22884:SF293; HISTONE-LYSINE N-METHYLTRANSFERASE NSD2; 1. DR PANTHER; PTHR22884; SET DOMAIN PROTEINS; 1. DR Pfam; PF17907; AWS; 1. DR Pfam; PF17982; C5HCH; 1. DR Pfam; PF00505; HMG_box; 1. DR Pfam; PF00628; PHD; 1. DR Pfam; PF00855; PWWP; 2. DR Pfam; PF00856; SET; 1. DR SMART; SM00570; AWS; 1. DR SMART; SM00398; HMG; 1. DR SMART; SM00249; PHD; 4. DR SMART; SM00508; PostSET; 1. DR SMART; SM00293; PWWP; 2. DR SMART; SM00317; SET; 1. DR SUPFAM; SSF57903; FYVE/PHD zinc finger; 3. DR SUPFAM; SSF47095; HMG-box; 1. DR SUPFAM; SSF82199; SET domain; 1. DR SUPFAM; SSF63748; Tudor/PWWP/MBT; 2. DR PROSITE; PS51215; AWS; 1. DR PROSITE; PS50118; HMG_BOX_2; 1. DR PROSITE; PS50868; POST_SET; 1. DR PROSITE; PS50812; PWWP; 2. DR PROSITE; PS50280; SET; 1. DR PROSITE; PS01359; ZF_PHD_1; 2. DR PROSITE; PS50016; ZF_PHD_2; 2. DR Genevisible; Q8BVE8; MM. PE 1: Evidence at protein level; KW Alternative splicing; Chromatin regulator; Chromosome; DNA-binding; KW Metal-binding; Methyltransferase; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; S-adenosyl-L-methionine; Transcription; KW Transcription regulation; Transferase; Zinc; Zinc-finger. FT CHAIN 1..1365 FT /note="Histone-lysine N-methyltransferase NSD2" FT /id="PRO_0000259520" FT DOMAIN 222..286 FT /note="PWWP 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00162" FT DOMAIN 880..942 FT /note="PWWP 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00162" FT DOMAIN 1011..1061 FT /note="AWS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00562" FT DOMAIN 1063..1180 FT /note="SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT DOMAIN 1187..1203 FT /note="Post-SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155" FT DNA_BIND 453..521 FT /note="HMG box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267" FT ZN_FING 667..713 FT /note="PHD-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 714..770 FT /note="PHD-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 831..875 FT /note="PHD-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 1239..1286 FT /note="PHD-type 4; atypical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT REGION 149..169 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 373..455 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 513..567 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 594..658 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1206..1232 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1329..1365 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 386..400 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 519..566 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 602..627 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 642..656 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 1016 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:O96028" FT BINDING 1018 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:O96028" FT BINDING 1026 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:O96028" FT BINDING 1026 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:O96028" FT BINDING 1032 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:O96028" FT BINDING 1041 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:O96028" FT BINDING 1046 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:O96028" FT BINDING 1052 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:O96028" FT BINDING 1075 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250|UniProtKB:O96028" FT BINDING 1115..1118 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250|UniProtKB:O96028" FT BINDING 1141..1142 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250|UniProtKB:O96028" FT BINDING 1144 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:O96028" FT BINDING 1186 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250|UniProtKB:O96028" FT BINDING 1191 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:O96028" FT BINDING 1192 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000250|UniProtKB:O96028" FT BINDING 1193 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:O96028" FT BINDING 1198 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:O96028" FT MOD_RES 110 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 114 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O96028" FT MOD_RES 121 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 172 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O96028" FT MOD_RES 376 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O96028" FT MOD_RES 422 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O96028" FT VAR_SEQ 1..661 FT /note="Missing (in isoform RE-IIBP)" FT /evidence="ECO:0000303|PubMed:18172012" FT /id="VSP_044420" FT VAR_SEQ 1..519 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14621295" FT /id="VSP_021424" FT VAR_SEQ 520..522 FT /note="NGN -> MGM (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14621295" FT /id="VSP_021425" FT VAR_SEQ 558 FT /note="K -> KQ (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:14621295, FT ECO:0000303|PubMed:15489334" FT /id="VSP_021426" FT MUTAGEN 1117 FT /note="F->A: Reduction in class switch recombination of the FT immunoglobulin heavy chain in B cells." FT /evidence="ECO:0000269|PubMed:23241889" FT MUTAGEN 1138 FT /note="R->A: No methyltransferase activity." FT /evidence="ECO:0000269|PubMed:18172012" FT MUTAGEN 1142 FT /note="H->G: No methyltransferase activity." FT /evidence="ECO:0000269|PubMed:19483677" FT MUTAGEN 1144 FT /note="C->A: No methyltransferase activity." FT /evidence="ECO:0000269|PubMed:18172012" FT CONFLICT 757 FT /note="F -> L (in Ref. 4; BAC37342)" FT /evidence="ECO:0000305" FT CONFLICT 1019 FT /note="K -> T (in Ref. 1; ACE75882)" FT /evidence="ECO:0000305" FT CONFLICT 1345 FT /note="S -> L (in Ref. 5; AAH53454)" FT /evidence="ECO:0000305" SQ SEQUENCE 1365 AA; 152253 MW; D8DC3F687D3EA2C2 CRC64; MEFSIRKSPL SVQKVVKCMK MKQTPEILGS ANGKTQNCEV NHECSVFLSK AQLSNSLQEG VMQKFNGHDA LPFLPAEKLK DLTSCVFNGE PGAHDTKLCF EAQEVKGIGT PPNTTPIKNG SPEIKLKITK TYMNGKPLFE SSICGDGAAD VSQSEENEQK SDNKTRRNRK RSIKYDSLLE QGLVEAALVS KISSPADKKI PVKKESCPNT GRDRDLLLKY NVGDLVWSKV SGYPWWPCMV SADPLLHNHT KLKGQKKSAR QYHVQFFGDA PERAWIFEKS LVAFEGEEQF EKLCQESAKQ APTKAEKIKL LKPISGRLRA QWEMGIVQAE EAASMSIEER KAKFTFLYVG DQLHLNPQVA KEAGIVTEPL GEMVDSSGAS EEAAVDPGSV REEDIPTKRR RRTKRSSSAE NQEGDPGTDK STPPKMAEAE PKRGVGSPAG RKKSTGSAPR SRKGDSAAQF LVFCQKHRDE VVAEHPDASG EEIEELLGSQ WSMLNEKQKA RYNTKFSLMI SAQSEEDSGN GNGKKRSHTK RADDPAEDVD VEDAPRKRLR ADKHSLRKRE TITDKTARTS SYKAIEAASS LKSQAATKNL SDACKPLKKR NRASATASSA LGFNKSSSPS ASLTEHEVSD SPGDEPSESP YESADETQTE ASVSSKKSER GMAAKKEYVC QLCEKTGSLL LCEGPCCGAF HLACLGLSRR PEGRFTCTEC ASGIHSCFVC KESKMEVKRC VVNQCGKFYH EACVKKYPLT VFESRGFRCP LHSCMSCHAS NPSNPRPSKG KMMRCVRCPV AYHGGDACLA AGCSVIASNS IICTGHFTAR KGKRHHTHVN VSWCFVCSKG GSLLCCEACP AAFHPDCLNI EMPDGSWFCN DCRAGKKLHF QDIIWVKLGN YRWWPAEVCH PKNVPPNIQK MKHEIGEFPV FFFGSKDYYW THQARVFPYM EGDRGSRYQG VRGIGRVFKN ALQEAEARFN EVKLQREARE TQESERKPPP YKHIKVNKPY GKVQIYTADI SEIPKCNCKP TDENPCGSDS ECLNRMLMFE CHPQVCPAGE YCQNQCFTKR QYPETKIIKT DGKGWGLVAK RDIRKGEFVN EYVGELIDEE ECMARIKYAH ENDITHFYML TIDKDRIIDA GPKGNYSRFM NHSCQPNCET LKWTVNGDTR VGLFAVCDIP AGTELTFNYN LDCLGNEKTV CRCGASNCSG FLGDRPKTSA SLSSEEKGKK AKKKTRRRRA KGEGKRQSED ECFRCGDGGQ LVLCDRKFCT KAYHLSCLGL GKRPFGKWEC PWHHCDVCGK PSTSFCHLCP NSFCKEHQDG TAFRSTQDGQ SYCCEHDLRA DSSSSTKTEK PFPESLKSKG KRKKRRCWRR VTDGK //