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};
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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 Genevisible; Q8BVE8; MM.
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.
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
//
