NSD2_HUMAN
ID NSD2_HUMAN Reviewed; 1365 AA.
AC O96028; A2A2T2; A2A2T3; A2A2T4; A7MCZ1; D3DVQ2; O96031; Q4VBY8; Q672J1;
AC Q6IS00; Q86V01; Q9BZB4; Q9UI92; Q9UPR2;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Histone-lysine N-methyltransferase NSD2;
DE EC=2.1.1.357 {ECO:0000269|PubMed:19808676, ECO:0000269|PubMed:22099308, ECO:0000269|PubMed:27571355, ECO:0000269|PubMed:29728617};
DE AltName: Full=Multiple myeloma SET domain-containing protein {ECO:0000303|PubMed:9787135};
DE Short=MMSET {ECO:0000303|PubMed:9787135};
DE AltName: Full=Nuclear SET domain-containing protein 2;
DE AltName: Full=Protein trithorax-5;
DE AltName: Full=Wolf-Hirschhorn syndrome candidate 1 protein;
GN Name=NSD2 {ECO:0000312|HGNC:HGNC:12766};
GN Synonyms=KIAA1090, MMSET, TRX5, WHSC1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), TISSUE SPECIFICITY, AND
RP CHROMOSOMAL TRANSLOCATION WITH IGH.
RC TISSUE=Myeloma;
RX PubMed=9787135;
RA Chesi M., Nardini E., Lim R.S.C., Smith K.D., Kuehl W.M., Bergsagel P.L.;
RT "The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel
RT gene, MMSET, resulting in IgH/MMSET hybrid transcripts.";
RL Blood 92:3025-3034(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 3 AND 5), TISSUE
RP SPECIFICITY, AND CHROMOSOMAL TRANSLOCATION WITH IGH.
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, AND DNA-BINDING.
RX PubMed=11152655; DOI=10.1165/ajrcmb.24.1.4224;
RA Garlisi C.G., Uss A.S., Xiao H., Tian F., Sheridan K.E., Wang L.,
RA Motasim Billah M., Egan R.W., Stranick K.S., Umland S.P.;
RT "A unique mRNA initiated within a middle intron of WHSC1/MMSET encodes a
RT DNA binding protein that suppresses human IL-5 transcription.";
RL Am. J. Respir. Cell Mol. Biol. 24:90-98(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7), AND SUBCELLULAR LOCATION.
RX PubMed=15677557; DOI=10.1182/blood-2004-09-3704;
RA Keats J.J., Maxwell C.A., Taylor B.J., Hendzel M.J., Chesi M.,
RA Bergsagel P.L., Larratt L.M., Mant M.J., Reiman T., Belch A.R.,
RA Pilarski L.M.;
RT "Overexpression of transcripts originating from the MMSET locus
RT characterizes all t(4;14)(p16;q32)-positive multiple myeloma patients.";
RL Blood 105:4060-4069(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Angrand P.-O., Valvatne H., Jeanmougin F., Adamson A., van der Hoeven F.,
RA Olsen L., Tekotte H., Huang N., Poch O., Lamerdin J., Chambon P.,
RA Losson R., Stewart A., Aasland R.;
RT "Mammalian trithorax- and ASH1-like proteins: putative chromatin regulators
RT which contain PHD fingers and SET domains.";
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4 AND 6).
RC TISSUE=Ovary, and Spleen;
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 [12]
RP CHROMOSOMAL TRANSLOCATION WITH IGH.
RX PubMed=10945609;
RA Malgeri U., Baldini L., Perfetti V., Fabris S., Vignarelli M.C.,
RA Colombo G., Lotti V., Compasso S., Bogni S., Lombardi L., Maiolo A.T.,
RA Neri A.;
RT "Detection of t(4;14)(p16.3;q32) chromosomal translocation in multiple
RT myeloma by reverse transcription-polymerase chain reaction analysis of IGH-
RT MMSET fusion transcripts.";
RL Cancer Res. 60:4058-4061(2000).
RN [13]
RP CHROMOSOMAL TRANSLOCATION WITH IGH.
RX PubMed=11337357; DOI=10.1016/s0002-9440(10)64115-6;
RA Perfetti V., Coluccia A.M., Intini D., Malgeri U., Vignarelli M.C.,
RA Casarini S., Merlini G., Neri A.;
RT "Translocation T(4;14)(p16.3;q32) is a recurrent genetic lesion in primary
RT amyloidosis.";
RL Am. J. Pathol. 158:1599-1603(2001).
RN [14]
RP CHROMOSOMAL TRANSLOCATION WITH IGH.
RX PubMed=12433679; DOI=10.1182/blood-2002-09-2801;
RA Santra M., Zhan F., Tian E., Barlogie B., Shaughnessy J. Jr.;
RT "A subset of multiple myeloma harboring the t(4;14)(p16;q32) translocation
RT lacks FGFR3 expression but maintains an IGH/MMSET fusion transcript.";
RL Blood 101:2374-2376(2003).
RN [15]
RP CHROMOSOMAL TRANSLOCATION WITH IGH.
RX PubMed=15257719; DOI=10.1111/j.1365-2141.2004.05048.x;
RA Intini D., Fabris S., Storlazzi T., Otsuki T., Ciceri G., Verdelli D.,
RA Lombardi L., Rocchi M., Neri A.;
RT "Identification of a novel IGH-MMSET fusion transcript in a human myeloma
RT cell line with the t(4;14)(p16.3;q32) chromosomal translocation.";
RL Br. J. Haematol. 126:437-439(2004).
RN [16]
RP FUNCTION.
RX PubMed=16115125; DOI=10.1111/j.1365-2141.2005.05664.x;
RA Hudlebusch H.R., Theilgaard-Moench K., Lodahl M., Johnsen H.E.,
RA Rasmussen T.;
RT "Identification of ID-1 as a potential target gene of MMSET in multiple
RT myeloma.";
RL Br. J. Haematol. 130:700-708(2005).
RN [17]
RP SUBCELLULAR LOCATION.
RX PubMed=16197452; DOI=10.1111/j.1365-2141.2005.05741.x;
RA Todoerti K., Ronchetti D., Agnelli L., Castellani S., Marelli S.,
RA Deliliers G.L., Zanella A., Lombardi L., Neri A.;
RT "Transcription repression activity is associated with the type I isoform of
RT the MMSET gene involved in t(4;14) in multiple myeloma.";
RL Br. J. Haematol. 131:214-218(2005).
RN [18]
RP INVOLVEMENT IN WHS.
RX PubMed=15734578; DOI=10.1016/j.tig.2005.01.008;
RA Bergemann A.D., Cole F., Hirschhorn K.;
RT "The etiology of Wolf-Hirschhorn syndrome.";
RL Trends Genet. 21:188-195(2005).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-544, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [20]
RP FUNCTION, AND TISSUE SPECIFICITY.
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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-121 AND THR-544, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [23]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=19808676; DOI=10.1074/jbc.m109.034462;
RA Li Y., Trojer P., Xu C.F., Cheung P., Kuo A., Drury W.J. III, Qiao Q.,
RA Neubert T.A., Xu R.M., Gozani O., Reinberg D.;
RT "The target of the NSD family of histone lysine methyltransferases depends
RT on the nature of the substrate.";
RL J. Biol. Chem. 284:34283-34295(2009).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-110; THR-114; SER-121;
RP SER-376 AND THR-544, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-544, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [26]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF TYR-1092 AND TYR-1179.
RX PubMed=22099308; DOI=10.1016/j.molcel.2011.08.042;
RA Kuo A.J., Cheung P., Chen K., Zee B.M., Kioi M., Lauring J., Xi Y.,
RA Park B.H., Shi X., Garcia B.A., Li W., Gozani O.;
RT "NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic
RT programming.";
RL Mol. Cell 44:609-620(2011).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-110; SER-121; SER-172;
RP THR-422; THR-544 AND SER-614, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [29]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF TYR-1092; HIS-1142 AND
RP TYR-1179.
RX PubMed=29728617; DOI=10.1038/s41467-018-04127-6;
RA Zhuang L., Jang Y., Park Y.K., Lee J.E., Jain S., Froimchuk E., Broun A.,
RA Liu C., Gavrilova O., Ge K.;
RT "Depletion of Nsd2-mediated histone H3K36 methylation impairs adipose
RT tissue development and function.";
RL Nat. Commun. 9:1796-1796(2018).
RN [30] {ECO:0007744|PDB:5LSU}
RP X-RAY CRYSTALLOGRAPHY (2.14 ANGSTROMS) OF 973-1203 IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE AND ZINC, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=27571355; DOI=10.1021/acschembio.6b00308;
RA Tisi D., Chiarparin E., Tamanini E., Pathuri P., Coyle J.E., Hold A.,
RA Holding F.P., Amin N., Martin A.C., Rich S.J., Berdini V., Yon J.,
RA Acklam P., Burke R., Drouin L., Harmer J.E., Jeganathan F.,
RA van Montfort R.L., Newbatt Y., Tortorici M., Westlake M., Wood A.,
RA Hoelder S., Heightman T.D.;
RT "Structure of the Epigenetic Oncogene MMSET and Inhibition by N-Alkyl
RT Sinefungin Derivatives.";
RL ACS Chem. Biol. 11:3093-3105(2016).
RN [31] {ECO:0007744|PDB:6UE6, ECO:0007744|PDB:6XCG}
RP X-RAY CRYSTALLOGRAPHY (1.64 ANGSTROMS) OF 211-350.
RA Zhou M.Q., Dong A., Ingerman L.A., Hanley R.P., Bountra C.,
RA Arrowsmith C.H., Edwards A.M., Min J.;
RT "Histone-lysine N-methyltransferase NSD2-PWWP1 with compound UNC6934.";
RL Submitted (JUN-2020) to the PDB data bank.
CC -!- FUNCTION: Histone methyltransferase which specifically dimethylates
CC nucleosomal histone H3 at 'Lys-36' (H3K36me2) (PubMed:27571355,
CC PubMed:22099308, PubMed:19808676, PubMed:29728617). Also monomethylates
CC nucleosomal histone H3 at 'Lys-36' (H3K36me) in vitro
CC (PubMed:22099308). Does not trimethylate nucleosomal histone H3 at
CC 'Lys-36' (H3K36me3) (PubMed:22099308). However, specifically
CC trimethylates histone H3 at 'Lys-36' (H3K36me3) at euchromatic regions
CC in embryonic stem (ES) cells (By similarity). By methylating histone H3
CC at 'Lys-36', involved in the regulation of gene transcription during
CC various biological processes (PubMed:16115125, PubMed:22099308,
CC PubMed:29728617). In ES cells, associates with developmental
CC transcription factors such as SALL1 and represses inappropriate gene
CC transcription mediated by histone deacetylation (By similarity). During
CC heart development, associates with transcription factor NKX2-5 to
CC repress transcription of NKX2-5 target genes (By similarity). Plays an
CC essential role in adipogenesis, by regulating expression of genes
CC involved in pre-adipocyte differentiation (PubMed:29728617). During T-
CC 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 (By similarity). During
CC B-cell development, required for the generation of the B1 lineage (By
CC similarity). During B2 cell activation, may contribute to the control
CC of isotype class switch recombination (CRS), splenic germinal center
CC formation, and the humoral immune response (By similarity). Plays a
CC role in class switch recombination of the immunoglobulin heavy chain
CC (IgH) locus during B-cell activation (By similarity). By regulating the
CC methylation of histone H3 at 'Lys-36' and histone H4 at 'Lys-20' at the
CC IgH locus, involved in TP53BP1 recruitment to the IgH switch region and
CC promotes the transcription of IgA (By similarity).
CC {ECO:0000250|UniProtKB:Q8BVE8, ECO:0000269|PubMed:16115125,
CC ECO:0000269|PubMed:19808676, ECO:0000269|PubMed:22099308,
CC ECO:0000269|PubMed:27571355, ECO:0000269|PubMed:29728617}.
CC -!- FUNCTION: [Isoform 1]: Histone methyltransferase which specifically
CC dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2).
CC {ECO:0000269|PubMed:22099308}.
CC -!- FUNCTION: [Isoform 4]: Histone methyltransferase which specifically
CC dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2)
CC (PubMed:22099308). Methylation of histone H3 at 'Lys-27' is
CC controversial (PubMed:18172012, PubMed:22099308). Mono-, di- or tri-
CC methylates histone H3 at 'Lys-27' (H3K27me, H3K27me2 and H3K27me3)
CC (PubMed:18172012). Does not methylate histone H3 at 'Lys-27'
CC (PubMed:22099308). May act as a transcription regulator that binds DNA
CC and suppresses IL5 transcription through HDAC recruitment
CC (PubMed:11152655, PubMed:18172012). {ECO:0000269|PubMed:11152655,
CC ECO:0000269|PubMed:18172012, ECO:0000269|PubMed:22099308}.
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:19808676, ECO:0000269|PubMed:22099308};
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:19808676, ECO:0000269|PubMed:22099308,
CC ECO:0000269|PubMed:27571355, ECO:0000269|PubMed:29728617};
CC -!- SUBUNIT: Interacts with HDAC1. Interacts (via PHD-type zinc fingers 1,
CC 2 and 3) with SALL1. Interacts (via PHD-type 1, 2 and 3) with SALL4.
CC Interacts with NANOG. Interacts with OGT. Interacts (via HMG box) with
CC NKX2-5. {ECO:0000250|UniProtKB:Q8BVE8}.
CC -!- INTERACTION:
CC O96028; P10275: AR; NbExp=5; IntAct=EBI-2693298, EBI-608057;
CC O96028; Q8N7B1: HORMAD2; NbExp=3; IntAct=EBI-2693298, EBI-13346145;
CC O96028; Q14676: MDC1; NbExp=3; IntAct=EBI-2693298, EBI-495644;
CC O96028; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-2693298, EBI-742388;
CC O96028-1; Q14676: MDC1; NbExp=3; IntAct=EBI-15910280, EBI-495644;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15677557,
CC ECO:0000269|PubMed:16197452}. Chromosome
CC {ECO:0000250|UniProtKB:Q8BVE8}. Note=In embryonic stem (ES) cells,
CC localizes to small foci, probably corresponding to euchromatin (By
CC similarity). In B-cells, localizes to Ig heavy chain switch region
CC during class switch recombination (By similarity).
CC {ECO:0000250|UniProtKB:Q8BVE8}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus
CC {ECO:0000269|PubMed:15677557, ECO:0000269|PubMed:16197452}. Chromosome
CC {ECO:0000269|PubMed:15677557}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Nucleus
CC {ECO:0000269|PubMed:15677557, ECO:0000269|PubMed:16197452}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm
CC {ECO:0000269|PubMed:15677557, ECO:0000269|PubMed:16197452}. Nucleus,
CC nucleolus {ECO:0000269|PubMed:15677557, ECO:0000269|PubMed:16197452}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1; Synonyms=MMSET type II {ECO:0000303|PubMed:9787135};
CC IsoId=O96028-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O96028-2; Sequence=VSP_021414, VSP_021423;
CC Name=3; Synonyms=MMSET type I {ECO:0000303|PubMed:9787135};
CC IsoId=O96028-3; Sequence=VSP_021419, VSP_021422;
CC Name=4; Synonyms=RE-IIBP {ECO:0000303|PubMed:11152655}, IL-5 promoter
CC REII-region-binding protein {ECO:0000303|PubMed:11152655};
CC IsoId=O96028-4; Sequence=VSP_021413;
CC Name=5;
CC IsoId=O96028-5; Sequence=VSP_021420, VSP_021421;
CC Name=6;
CC IsoId=O96028-6; Sequence=VSP_021417, VSP_021418;
CC Name=7;
CC IsoId=O96028-7; Sequence=VSP_021415, VSP_021416;
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:9618163, PubMed:18172012).
CC Predominantly expressed in thymus and testis (PubMed:9787135,
CC PubMed:18172012). {ECO:0000269|PubMed:18172012,
CC ECO:0000269|PubMed:9618163, ECO:0000269|PubMed:9787135}.
CC -!- DISEASE: Note=A chromosomal aberration involving NSD2 is a cause of
CC multiple myeloma tumors. Translocation t(4;14)(p16.3;q32.3) with IgH.
CC {ECO:0000269|PubMed:10945609, ECO:0000269|PubMed:11337357,
CC ECO:0000269|PubMed:12433679, ECO:0000269|PubMed:15257719,
CC ECO:0000269|PubMed:9618163, ECO:0000269|PubMed:9787135}.
CC -!- DISEASE: Note=NSD2 is located in the Wolf-Hirschhorn syndrome (WHS)
CC critical region. WHS results from by sub-telomeric deletions in the
CC short arm of chromosome 4. NSD2 is deleted in every case, however
CC deletion of linked genes contributes to both the severity of the core
CC characteristics and the presence of the additional syndromic problems.
CC {ECO:0000269|PubMed:15734578}.
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
CC (PubMed:19808676). However, dimethylation of nucleosomal histone H3 at
CC 'Lys-36' (H3K36me2) is likely to be the physiological reaction
CC catalyzed by NSD2 (PubMed:19808676, PubMed:22099308).
CC {ECO:0000269|PubMed:19808676, ECO:0000269|PubMed:22099308}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA83042.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/WHSC1ID42809ch4p16.html";
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; AF071593; AAC24150.1; -; mRNA.
DR EMBL; AF071594; AAC24151.1; -; mRNA.
DR EMBL; AF083386; AAD19343.1; -; mRNA.
DR EMBL; AF083387; AAD21770.1; -; mRNA.
DR EMBL; AF083388; AAD21771.1; -; mRNA.
DR EMBL; AF083389; AAD19344.1; -; mRNA.
DR EMBL; AF083390; AAD19345.1; -; mRNA.
DR EMBL; AF083391; AAD19346.1; -; mRNA.
DR EMBL; AF178206; AAF23369.1; -; Genomic_DNA.
DR EMBL; AF178199; AAF23369.1; JOINED; Genomic_DNA.
DR EMBL; AF178198; AAF23369.1; JOINED; Genomic_DNA.
DR EMBL; AF178202; AAF23369.1; JOINED; Genomic_DNA.
DR EMBL; AF178204; AAF23369.1; JOINED; Genomic_DNA.
DR EMBL; AF178205; AAF23369.1; JOINED; Genomic_DNA.
DR EMBL; AF178203; AAF23369.1; JOINED; Genomic_DNA.
DR EMBL; AF178201; AAF23369.1; JOINED; Genomic_DNA.
DR EMBL; AF178200; AAF23369.1; JOINED; Genomic_DNA.
DR EMBL; AF178219; AAF23370.1; -; Genomic_DNA.
DR EMBL; AF178198; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178199; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178200; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178202; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178204; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178207; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178216; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178215; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178214; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178213; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178212; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178211; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178210; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178209; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178208; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178218; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178217; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178205; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178203; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF178201; AAF23370.1; JOINED; Genomic_DNA.
DR EMBL; AF330040; AAK00344.1; -; mRNA.
DR EMBL; AY694128; AAU09264.1; -; mRNA.
DR EMBL; AJ007042; CAB45386.1; -; mRNA.
DR EMBL; AB029013; BAA83042.2; ALT_INIT; mRNA.
DR EMBL; AK289697; BAF82386.1; -; mRNA.
DR EMBL; AC105448; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL132868; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471131; EAW82548.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82552.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82557.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82553.1; -; Genomic_DNA.
DR EMBL; CH471131; EAW82556.1; -; Genomic_DNA.
DR EMBL; BC052254; AAH52254.1; -; mRNA.
DR EMBL; BC070176; AAH70176.1; -; mRNA.
DR EMBL; BC094825; AAH94825.2; -; mRNA.
DR EMBL; BC141815; AAI41816.1; -; mRNA.
DR EMBL; BC152412; AAI52413.1; -; mRNA.
DR CCDS; CCDS3356.1; -. [O96028-3]
DR CCDS; CCDS33940.1; -. [O96028-1]
DR CCDS; CCDS46999.1; -. [O96028-5]
DR RefSeq; NP_001035889.1; NM_001042424.2. [O96028-1]
DR RefSeq; NP_015627.1; NM_007331.1. [O96028-5]
DR RefSeq; NP_579877.1; NM_133330.2. [O96028-1]
DR RefSeq; NP_579878.1; NM_133331.2. [O96028-1]
DR RefSeq; NP_579889.1; NM_133334.2. [O96028-3]
DR RefSeq; NP_579890.1; NM_133335.3. [O96028-1]
DR RefSeq; XP_005248058.1; XM_005248001.3. [O96028-1]
DR RefSeq; XP_005248062.1; XM_005248005.2. [O96028-3]
DR RefSeq; XP_006713977.1; XM_006713914.3. [O96028-3]
DR RefSeq; XP_011511859.1; XM_011513557.2. [O96028-1]
DR RefSeq; XP_011511862.1; XM_011513560.2. [O96028-4]
DR RefSeq; XP_016864076.1; XM_017008587.1. [O96028-4]
DR RefSeq; XP_016864077.1; XM_017008588.1. [O96028-4]
DR PDB; 5LSU; X-ray; 2.14 A; A/B=973-1203.
DR PDB; 5VC8; X-ray; 1.80 A; A/B=211-350.
DR PDB; 6UE6; X-ray; 2.40 A; A/B/C/D/E/F/G/H=211-350.
DR PDB; 6XCG; X-ray; 1.64 A; A/B/C=211-350.
DR PDB; 7CRO; EM; 3.75 A; I=661-1365.
DR PDB; 7E8D; EM; 2.80 A; K=973-1226.
DR PDB; 7LMT; X-ray; 2.27 A; A/B/C/D/E/F/G/H=211-350.
DR PDB; 7MDN; X-ray; 2.42 A; A/B/C/D/E/F/G/H=211-350.
DR PDBsum; 5LSU; -.
DR PDBsum; 5VC8; -.
DR PDBsum; 6UE6; -.
DR PDBsum; 6XCG; -.
DR PDBsum; 7CRO; -.
DR PDBsum; 7E8D; -.
DR PDBsum; 7LMT; -.
DR PDBsum; 7MDN; -.
DR AlphaFoldDB; O96028; -.
DR SMR; O96028; -.
DR BioGRID; 113306; 243.
DR DIP; DIP-57224N; -.
DR IntAct; O96028; 55.
DR MINT; O96028; -.
DR STRING; 9606.ENSP00000372351; -.
DR BindingDB; O96028; -.
DR ChEMBL; CHEMBL3108645; -.
DR iPTMnet; O96028; -.
DR PhosphoSitePlus; O96028; -.
DR BioMuta; NSD2; -.
DR EPD; O96028; -.
DR jPOST; O96028; -.
DR MassIVE; O96028; -.
DR MaxQB; O96028; -.
DR PaxDb; O96028; -.
DR PeptideAtlas; O96028; -.
DR PRIDE; O96028; -.
DR ProteomicsDB; 228; -.
DR ProteomicsDB; 51216; -. [O96028-1]
DR ProteomicsDB; 51217; -. [O96028-2]
DR ProteomicsDB; 51218; -. [O96028-3]
DR ProteomicsDB; 51219; -. [O96028-4]
DR ProteomicsDB; 51220; -. [O96028-5]
DR ProteomicsDB; 51221; -. [O96028-6]
DR ProteomicsDB; 51222; -. [O96028-7]
DR Antibodypedia; 8608; 198 antibodies from 31 providers.
DR DNASU; 7468; -.
DR Ensembl; ENST00000312087.10; ENSP00000308780.6; ENSG00000109685.19. [O96028-3]
DR Ensembl; ENST00000353275.9; ENSP00000329167.5; ENSG00000109685.19. [O96028-3]
DR Ensembl; ENST00000382888.3; ENSP00000372344.3; ENSG00000109685.19. [O96028-2]
DR Ensembl; ENST00000382891.9; ENSP00000372347.5; ENSG00000109685.19. [O96028-1]
DR Ensembl; ENST00000382892.6; ENSP00000372348.2; ENSG00000109685.19. [O96028-1]
DR Ensembl; ENST00000382895.7; ENSP00000372351.3; ENSG00000109685.19. [O96028-1]
DR Ensembl; ENST00000398261.6; ENSP00000381311.1; ENSG00000109685.19. [O96028-3]
DR Ensembl; ENST00000420906.6; ENSP00000399251.2; ENSG00000109685.19. [O96028-5]
DR Ensembl; ENST00000503128.5; ENSP00000425761.1; ENSG00000109685.19. [O96028-3]
DR Ensembl; ENST00000508803.6; ENSP00000423972.1; ENSG00000109685.19. [O96028-1]
DR Ensembl; ENST00000514045.5; ENSP00000421681.1; ENSG00000109685.19. [O96028-5]
DR Ensembl; ENST00000678714.1; ENSP00000504221.1; ENSG00000109685.19. [O96028-7]
DR GeneID; 7468; -.
DR KEGG; hsa:7468; -.
DR MANE-Select; ENST00000508803.6; ENSP00000423972.1; NM_001042424.3; NP_001035889.1.
DR UCSC; uc003gdy.2; human. [O96028-1]
DR CTD; 7468; -.
DR DisGeNET; 7468; -.
DR GeneCards; NSD2; -.
DR HGNC; HGNC:12766; NSD2.
DR HPA; ENSG00000109685; Low tissue specificity.
DR MalaCards; NSD2; -.
DR MIM; 602952; gene.
DR neXtProt; NX_O96028; -.
DR OpenTargets; ENSG00000109685; -.
DR Orphanet; 280; Wolf-Hirschhorn syndrome.
DR PharmGKB; PA37369; -.
DR VEuPathDB; HostDB:ENSG00000109685; -.
DR eggNOG; KOG1081; Eukaryota.
DR GeneTree; ENSGT00940000157429; -.
DR HOGENOM; CLU_004494_2_1_1; -.
DR InParanoid; O96028; -.
DR OMA; CCTKAYH; -.
DR OrthoDB; 507784at2759; -.
DR PhylomeDB; O96028; -.
DR TreeFam; TF329088; -.
DR BioCyc; MetaCyc:HS03249-MON; -.
DR BRENDA; 2.1.1.356; 2681.
DR BRENDA; 2.1.1.357; 2681.
DR BRENDA; 2.1.1.359; 2681.
DR PathwayCommons; O96028; -.
DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR SignaLink; O96028; -.
DR SIGNOR; O96028; -.
DR BioGRID-ORCS; 7468; 35 hits in 1119 CRISPR screens.
DR ChiTaRS; WHSC1; human.
DR GeneWiki; WHSC1; -.
DR GenomeRNAi; 7468; -.
DR Pharos; O96028; Tchem.
DR PRO; PR:O96028; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; O96028; protein.
DR Bgee; ENSG00000109685; Expressed in ventricular zone and 195 other tissues.
DR ExpressionAtlas; O96028; baseline and differential.
DR Genevisible; O96028; HS.
DR GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0046975; F:histone methyltransferase activity (H3-K36 specific); IBA:GO_Central.
DR GO; GO:0042799; F:histone methyltransferase activity (H4-K20 specific); TAS:Reactome.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; TAS:Reactome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0003289; P:atrial septum primum morphogenesis; IEA:Ensembl.
DR GO; GO:0003290; P:atrial septum secundum morphogenesis; IEA:Ensembl.
DR GO; GO:0060348; P:bone development; IEA:Ensembl.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006302; P:double-strand break repair; TAS:Reactome.
DR GO; GO:0010452; P:histone H3-K36 methylation; IEA:Ensembl.
DR GO; GO:0034770; P:histone H4-K20 methylation; IEA:Ensembl.
DR GO; GO:0003149; P:membranous septum morphogenesis; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0048298; P:positive regulation of isotype switching to IgA isotypes; IEA:Ensembl.
DR GO; GO:2001032; P:regulation of double-strand break repair via nonhomologous end joining; IEA:Ensembl.
DR GO; GO:0070201; P:regulation of establishment of protein localization; IEA:Ensembl.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR Gene3D; 1.10.30.10; -; 1.
DR Gene3D; 2.170.270.10; -; 1.
DR Gene3D; 3.30.40.10; -; 4.
DR InterPro; IPR006560; AWS_dom.
DR InterPro; IPR041306; C5HCH.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR InterPro; IPR003616; Post-SET_dom.
DR InterPro; IPR000313; PWWP_dom.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
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 Pfam; PF17907; AWS; 1.
DR Pfam; PF17982; C5HCH; 1.
DR Pfam; PF00505; HMG_box; 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; SM00184; RING; 2.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF47095; SSF47095; 1.
DR SUPFAM; SSF57903; SSF57903; 3.
DR SUPFAM; SSF82199; SSF82199; 1.
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 3D-structure; Alternative splicing; Chromatin regulator;
KW Chromosomal rearrangement; Chromosome; Cytoplasm; DNA-binding;
KW Metal-binding; Methyltransferase; Nucleus; Phosphoprotein; Proto-oncogene;
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_0000259519"
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..170
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 376..455
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 516..658
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1207..1232
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1333..1365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 385..408
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 567..590
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 602..630
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 642..658
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:0000269|PubMed:27571355,
FT ECO:0007744|PDB:5LSU"
FT BINDING 1018
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27571355,
FT ECO:0007744|PDB:5LSU"
FT BINDING 1026
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27571355,
FT ECO:0007744|PDB:5LSU"
FT BINDING 1026
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27571355,
FT ECO:0007744|PDB:5LSU"
FT BINDING 1032
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:27571355,
FT ECO:0007744|PDB:5LSU"
FT BINDING 1041
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27571355,
FT ECO:0007744|PDB:5LSU"
FT BINDING 1046
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27571355,
FT ECO:0007744|PDB:5LSU"
FT BINDING 1052
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:27571355,
FT ECO:0007744|PDB:5LSU"
FT BINDING 1075
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:27571355,
FT ECO:0007744|PDB:5LSU"
FT BINDING 1115..1118
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:27571355,
FT ECO:0007744|PDB:5LSU"
FT BINDING 1141..1142
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:27571355,
FT ECO:0007744|PDB:5LSU"
FT BINDING 1144
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:27571355,
FT ECO:0007744|PDB:5LSU"
FT BINDING 1186
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:27571355,
FT ECO:0007744|PDB:5LSU"
FT BINDING 1191
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:27571355,
FT ECO:0007744|PDB:5LSU"
FT BINDING 1192
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:27571355,
FT ECO:0007744|PDB:5LSU"
FT BINDING 1193
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:27571355,
FT ECO:0007744|PDB:5LSU"
FT BINDING 1198
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:27571355,
FT ECO:0007744|PDB:5LSU"
FT MOD_RES 110
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 114
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 121
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 172
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 376
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 422
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 544
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 614
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..781
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11152655,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_021413"
FT VAR_SEQ 1..652
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10470851,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_021414"
FT VAR_SEQ 255..273
FT /note="QKKSARQYHVQFFGDAPER -> IFKSKKFEHLKTSQIVLKD (in
FT isoform 7)"
FT /evidence="ECO:0000303|PubMed:15677557"
FT /id="VSP_021415"
FT VAR_SEQ 274..1365
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:15677557"
FT /id="VSP_021416"
FT VAR_SEQ 472..484
FT /note="VAEHPDASGEEIE -> STKLCFMLASFRI (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_021417"
FT VAR_SEQ 485..1365
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_021418"
FT VAR_SEQ 628..647
FT /note="VSDSPGDEPSESPYESADET -> LLWEPTPVKLDLNPAALYCT (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9618163,
FT ECO:0000303|PubMed:9787135"
FT /id="VSP_021419"
FT VAR_SEQ 629
FT /note="S -> K (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:9618163"
FT /id="VSP_021420"
FT VAR_SEQ 630..1365
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:9618163"
FT /id="VSP_021421"
FT VAR_SEQ 648..1365
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9618163,
FT ECO:0000303|PubMed:9787135"
FT /id="VSP_021422"
FT VAR_SEQ 653..712
FT /note="VSSKKSERGVTAKKEYVCQLCEKPGSLLLCEGPCCGAFHLACLGLSRRPEGR
FT FTCSECAS -> MAGSFCWRMLGLVSKVGNRARCFSSMAASEEELLDFSGSELQFNSCS
FT LHLSLHPFFNFLL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10470851,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_021423"
FT MUTAGEN 1092
FT /note="Y->A: Loss of methyltransferase activity. Reduces
FT levels of H3K36me2 in preadipocytes; when associated with
FT A-1179."
FT /evidence="ECO:0000269|PubMed:22099308,
FT ECO:0000269|PubMed:29728617"
FT MUTAGEN 1142
FT /note="H->G: Reduces levels of H3K36me2 in preadipocytes;
FT when associated with A-1179."
FT /evidence="ECO:0000269|PubMed:29728617"
FT MUTAGEN 1179
FT /note="Y->A: Loss of methyltransferase activity. Reduces
FT levels of H3K36me2 in preadipocytes; when associated with
FT A-1092 or G-1142."
FT /evidence="ECO:0000269|PubMed:22099308,
FT ECO:0000269|PubMed:29728617"
FT CONFLICT 210
FT /note="T -> A (in Ref. 5; AAU09264)"
FT /evidence="ECO:0000305"
FT HELIX 215..217
FT /evidence="ECO:0007829|PDB:6UE6"
FT STRAND 225..228
FT /evidence="ECO:0007829|PDB:6XCG"
FT STRAND 236..240
FT /evidence="ECO:0007829|PDB:6XCG"
FT TURN 244..246
FT /evidence="ECO:0007829|PDB:6XCG"
FT STRAND 249..252
FT /evidence="ECO:0007829|PDB:6XCG"
FT HELIX 253..255
FT /evidence="ECO:0007829|PDB:6XCG"
FT STRAND 260..266
FT /evidence="ECO:0007829|PDB:6XCG"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:6XCG"
FT STRAND 272..277
FT /evidence="ECO:0007829|PDB:6XCG"
FT HELIX 278..280
FT /evidence="ECO:0007829|PDB:6XCG"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:6XCG"
FT HELIX 287..289
FT /evidence="ECO:0007829|PDB:6XCG"
FT HELIX 290..300
FT /evidence="ECO:0007829|PDB:6XCG"
FT HELIX 304..310
FT /evidence="ECO:0007829|PDB:6XCG"
FT HELIX 316..333
FT /evidence="ECO:0007829|PDB:6XCG"
FT HELIX 337..344
FT /evidence="ECO:0007829|PDB:6XCG"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:5VC8"
FT HELIX 974..981
FT /evidence="ECO:0007829|PDB:5LSU"
FT HELIX 1010..1012
FT /evidence="ECO:0007829|PDB:5LSU"
FT STRAND 1022..1024
FT /evidence="ECO:0007829|PDB:5LSU"
FT STRAND 1028..1030
FT /evidence="ECO:0007829|PDB:7E8D"
FT HELIX 1033..1036
FT /evidence="ECO:0007829|PDB:5LSU"
FT TURN 1043..1045
FT /evidence="ECO:0007829|PDB:5LSU"
FT TURN 1047..1050
FT /evidence="ECO:0007829|PDB:5LSU"
FT HELIX 1056..1059
FT /evidence="ECO:0007829|PDB:5LSU"
FT STRAND 1065..1069
FT /evidence="ECO:0007829|PDB:5LSU"
FT STRAND 1071..1081
FT /evidence="ECO:0007829|PDB:5LSU"
FT STRAND 1088..1092
FT /evidence="ECO:0007829|PDB:5LSU"
FT STRAND 1095..1097
FT /evidence="ECO:0007829|PDB:5LSU"
FT HELIX 1099..1111
FT /evidence="ECO:0007829|PDB:5LSU"
FT STRAND 1119..1123
FT /evidence="ECO:0007829|PDB:5LSU"
FT STRAND 1126..1129
FT /evidence="ECO:0007829|PDB:5LSU"
FT TURN 1130..1132
FT /evidence="ECO:0007829|PDB:5LSU"
FT HELIX 1136..1139
FT /evidence="ECO:0007829|PDB:5LSU"
FT STRAND 1147..1155
FT /evidence="ECO:0007829|PDB:5LSU"
FT STRAND 1158..1167
FT /evidence="ECO:0007829|PDB:5LSU"
FT STRAND 1173..1177
FT /evidence="ECO:0007829|PDB:7E8D"
FT HELIX 1179..1181
FT /evidence="ECO:0007829|PDB:5LSU"
FT STRAND 1183..1185
FT /evidence="ECO:0007829|PDB:5LSU"
FT CONFLICT O96028-2:26
FT /note="M -> V (in Ref. 7; BAA83042 and 11; AAI52413)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1365 AA; 152258 MW; 7B3128E1FA893AAA CRC64;
MEFSIKQSPL SVQSVVKCIK MKQAPEILGS ANGKTPSCEV NRECSVFLSK AQLSSSLQEG
VMQKFNGHDA LPFIPADKLK DLTSRVFNGE PGAHDAKLRF ESQEMKGIGT PPNTTPIKNG
SPEIKLKITK TYMNGKPLFE SSICGDSAAD VSQSEENGQK PENKARRNRK RSIKYDSLLE
QGLVEAALVS KISSPSDKKI PAKKESCPNT GRDKDHLLKY NVGDLVWSKV SGYPWWPCMV
SADPLLHSYT KLKGQKKSAR QYHVQFFGDA PERAWIFEKS LVAFEGEGQF EKLCQESAKQ
APTKAEKIKL LKPISGKLRA QWEMGIVQAE EAASMSVEER KAKFTFLYVG DQLHLNPQVA
KEAGIAAESL GEMAESSGVS EEAAENPKSV REECIPMKRR RRAKLCSSAE TLESHPDIGK
STPQKTAEAD PRRGVGSPPG RKKTTVSMPR SRKGDAASQF LVFCQKHRDE VVAEHPDASG
EEIEELLRSQ WSLLSEKQRA RYNTKFALVA PVQAEEDSGN VNGKKRNHTK RIQDPTEDAE
AEDTPRKRLR TDKHSLRKRD TITDKTARTS SYKAMEAASS LKSQAATKNL SDACKPLKKR
NRASTAASSA LGFSKSSSPS ASLTENEVSD SPGDEPSESP YESADETQTE VSVSSKKSER
GVTAKKEYVC QLCEKPGSLL LCEGPCCGAF HLACLGLSRR PEGRFTCSEC ASGIHSCFVC
KESKTDVKRC VVTQCGKFYH EACVKKYPLT VFESRGFRCP LHSCVSCHAS NPSNPRPSKG
KMMRCVRCPV AYHSGDACLA AGCSVIASNS IICTAHFTAR KGKRHHAHVN VSWCFVCSKG
GSLLCCESCP AAFHPDCLNI EMPDGSWFCN DCRAGKKLHF QDIIWVKLGN YRWWPAEVCH
PKNVPPNIQK MKHEIGEFPV FFFGSKDYYW THQARVFPYM EGDRGSRYQG VRGIGRVFKN
ALQEAEARFR EIKLQREARE TQESERKPPP YKHIKVNKPY GKVQIYTADI SEIPKCNCKP
TDENPCGFDS ECLNRMLMFE CHPQVCPAGE FCQNQCFTKR QYPETKIIKT DGKGWGLVAK
RDIRKGEFVN EYVGELIDEE ECMARIKHAH ENDITHFYML TIDKDRIIDA GPKGNYSRFM
NHSCQPNCET LKWTVNGDTR VGLFAVCDIP AGTELTFNYN LDCLGNEKTV CRCGASNCSG
FLGDRPKTST TLSSEEKGKK TKKKTRRRRA KGEGKRQSED ECFRCGDGGQ LVLCDRKFCT
KAYHLSCLGL GKRPFGKWEC PWHHCDVCGK PSTSFCHLCP NSFCKEHQDG TAFSCTPDGR
SYCCEHDLGA ASVRSTKTEK PPPEPGKPKG KRRRRRGWRR VTEGK
