Human Gene NSD2 (ENST00000312087.10_2) from GENCODE V47lift37
Description: Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2) (PubMed:27571355, PubMed:22099308, PubMed:19808676, PubMed:29728617, PubMed:33941880). Also monomethylates nucleosomal histone H3 at 'Lys-36' (H3K36me) in vitro (PubMed:22099308). Does not trimethylate nucleosomal histone H3 at 'Lys-36' (H3K36me3) (PubMed:22099308). However, specifically trimethylates histone H3 at 'Lys-36' (H3K36me3) at euchromatic regions in embryonic stem (ES) cells (By similarity). By methylating histone H3 at 'Lys-36', involved in the regulation of gene transcription during various biological processes (PubMed:16115125, PubMed:22099308, PubMed:29728617). In ES cells, associates with developmental transcription factors such as SALL1 and represses inappropriate gene transcription mediated by histone deacetylation (By similarity). During heart development, associates with transcription factor NKX2-5 to repress transcription of NKX2-5 target genes (By similarity). Plays an essential role in adipogenesis, by regulating expression of genes involved in pre-adipocyte differentiation (PubMed:29728617). During T- cell receptor (TCR) and CD28-mediated T-cell activation, promotes the transcription of transcription factor BCL6 which is required for follicular helper T (Tfh) cell differentiation (By similarity). During B-cell development, required for the generation of the B1 lineage (By similarity). During B2 cell activation, may contribute to the control of isotype class switch recombination (CRS), splenic germinal center formation, and the humoral immune response (By similarity). Plays a role in class switch recombination of the immunoglobulin heavy chain (IgH) locus during B-cell activation (By similarity). By regulating the methylation of histone H3 at 'Lys-36' and histone H4 at 'Lys-20' at the IgH locus, involved in TP53BP1 recruitment to the IgH switch region and promotes the transcription of IgA (By similarity). (from UniProt O96028) Gencode Transcript: ENST00000312087.10_2 Gencode Gene: ENSG00000109685.19_11 Transcript (Including UTRs) Position: hg19 chr4:1,894,572-1,983,930 Size: 89,359 Total Exon Count: 25 Strand: + Coding Region Position: hg19 chr4:1,902,382-1,944,128 Size: 41,747 Coding Exon Count: 9
ID:NSD2_HUMAN DESCRIPTION: RecName: Full=Histone-lysine N-methyltransferase NSD2; EC=2.1.1.43; AltName: Full=Multiple myeloma SET domain-containing protein; Short=MMSET; AltName: Full=Nuclear SET domain-containing protein 2; Short=NSD2; AltName: Full=Protein trithorax-5; AltName: Full=Wolf-Hirschhorn syndrome candidate 1 protein; Short=WHSC1; FUNCTION: Histone methyltransferase with histone H3 'Lys-27' (H3K27me) methyltransferase activity. Isoform RE-IIBP may act as a transcription regulator that binds DNA and suppresses IL5 transcription through HDAC recruitment. CATALYTIC ACTIVITY: S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. SUBCELLULAR LOCATION: Nucleus. Chromosome (Potential). SUBCELLULAR LOCATION: Isoform 4: Cytoplasm. TISSUE SPECIFICITY: Widely expressed. PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. DISEASE: Note=A chromosomal aberration involving WHSC1 is a cause of multiple myeloma tumors. Translocation t(4;14)(p16.3;q32.3) with IgH. DISEASE: Note=WHSC1 is located in the Wolf-Hirschhorn syndrome (WHS) critical region. WHS results from by sub-telomeric deletions in the short arm of chromosome 4. WHSC1 is deleted in every case, however deletion of linked genes contributes to both the severity of the core characteristics and the presence of the additional syndromic problems. SIMILARITY: Belongs to the histone-lysine methyltransferase family. SET2 subfamily. SIMILARITY: Contains 1 AWS domain. SIMILARITY: Contains 1 HMG box DNA-binding domain. SIMILARITY: Contains 4 PHD-type zinc fingers. SIMILARITY: Contains 1 post-SET domain. SIMILARITY: Contains 2 PWWP domains. SIMILARITY: Contains 1 SET domain. SEQUENCE CAUTION: Sequence=BAA83042.2; Type=Erroneous initiation; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/WHSC1ID42809ch4p16.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O96028
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0003677 DNA binding GO:0003682 chromatin binding GO:0005515 protein binding GO:0008168 methyltransferase activity GO:0016740 transferase activity GO:0018024 histone-lysine N-methyltransferase activity GO:0042799 histone methyltransferase activity (H4-K20 specific) GO:0043565 sequence-specific DNA binding GO:0046872 metal ion binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0003149 membranous septum morphogenesis GO:0003289 atrial septum primum morphogenesis GO:0003290 atrial septum secundum morphogenesis GO:0006303 double-strand break repair via nonhomologous end joining GO:0006325 chromatin organization GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0009653 anatomical structure morphogenesis GO:0010452 histone H3-K36 methylation GO:0032259 methylation GO:0034770 histone H4-K20 methylation GO:0048298 positive regulation of isotype switching to IgA isotypes GO:0060348 bone development GO:0070201 regulation of establishment of protein localization GO:2001032 regulation of double-strand break repair via nonhomologous end joining
BC032731 - Homo sapiens Wolf-Hirschhorn syndrome candidate 1, mRNA (cDNA clone IMAGE:5529759), containing frame-shift errors. AJ007042 - Homo sapiens mRNA for TRX5 protein. AF083386 - Homo sapiens putative WHSC1 protein (WHSC1) mRNA, complete cds. AF083387 - Homo sapiens putative WHSC1 protein (WHSC1) mRNA, alternative splice product missing exon 2, complete cds. AF083388 - Homo sapiens putative WHSC1 protein (WHSC1) mRNA, alternative splice product missing exons 2 and 3, complete cds. AF083389 - Homo sapiens putative WHSC1 protein (WHSC1) mRNA, alternative splice product with complete exon 12, complete cds. AF083390 - Homo sapiens putative WHSC1 protein (WHSC1) mRNA, alternative splice product with differentially spliced exon 12, complete cds. AF071593 - Homo sapiens MMSET type II (WHSC1) mRNA, complete cds. AB384560 - Synthetic construct DNA, clone: pF1KA1090, Homo sapiens WHSC1 gene for histone-lysine N-methyltransferase NSD2, complete cds, without stop codon, in Flexi system. BC166668 - Synthetic construct Homo sapiens clone IMAGE:100066394, MGC:195531 Wolf-Hirschhorn syndrome candidate 1 (WHSC1) mRNA, encodes complete protein. BC110899 - Homo sapiens cDNA clone IMAGE:6173977, containing frame-shift errors. AF330040 - Homo sapiens IL-5 promoter REII-region-binding protein (REIIBP) mRNA, complete cds. BC144464 - Homo sapiens cDNA clone IMAGE:9052990. AB029013 - Homo sapiens mRNA for KIAA1090 protein, partial cds. BC094825 - Homo sapiens Wolf-Hirschhorn syndrome candidate 1, mRNA (cDNA clone IMAGE:6644981), complete cds. AK026939 - Homo sapiens cDNA: FLJ23286 fis, clone HEP09362, highly similar to AF083390 Homo sapiens putative WHSC1 protein mRNA. AK289697 - Homo sapiens cDNA FLJ77008 complete cds, highly similar to Homo sapiens Wolf-Hirschhorn syndrome candidate 1 (WHSC1), transcript variant 7, mRNA. BC052254 - Homo sapiens Wolf-Hirschhorn syndrome candidate 1, mRNA (cDNA clone IMAGE:6302332), complete cds. BC020545 - Homo sapiens Wolf-Hirschhorn syndrome candidate 1, mRNA (cDNA clone IMAGE:4398988), complete cds. AF083391 - Homo sapiens putative WHSC1 protein (WHSC1) mRNA, alternative splice product ending in intron 11, complete cds. JD505359 - Sequence 486383 from Patent EP1572962. JD106899 - Sequence 87923 from Patent EP1572962. JD136518 - Sequence 117542 from Patent EP1572962. JD441002 - Sequence 422026 from Patent EP1572962. JD265816 - Sequence 246840 from Patent EP1572962. JD293479 - Sequence 274503 from Patent EP1572962. JD457549 - Sequence 438573 from Patent EP1572962. JD342322 - Sequence 323346 from Patent EP1572962. JD522113 - Sequence 503137 from Patent EP1572962. JD347703 - Sequence 328727 from Patent EP1572962. JD535973 - Sequence 516997 from Patent EP1572962. JD055116 - Sequence 36140 from Patent EP1572962. BC141815 - Homo sapiens Wolf-Hirschhorn syndrome candidate 1, mRNA (cDNA clone IMAGE:40147994), complete cds. JD199898 - Sequence 180922 from Patent EP1572962. JD227025 - Sequence 208049 from Patent EP1572962. JD233605 - Sequence 214629 from Patent EP1572962. JD549906 - Sequence 530930 from Patent EP1572962. AF071594 - Homo sapiens MMSET type I (WHSC1) mRNA, complete cds. JD279611 - Sequence 260635 from Patent EP1572962. JD309833 - Sequence 290857 from Patent EP1572962. AY694128 - Homo sapiens multiple myeloma SET domain containing protein type III (WHSC1) mRNA, complete cds, alternatively spliced. BC070176 - Homo sapiens Wolf-Hirschhorn syndrome candidate 1, mRNA (cDNA clone IMAGE:6699237), partial cds. JD468072 - Sequence 449096 from Patent EP1572962. JD516537 - Sequence 497561 from Patent EP1572962. JD121285 - Sequence 102309 from Patent EP1572962. JD512127 - Sequence 493151 from Patent EP1572962. JD160405 - Sequence 141429 from Patent EP1572962. JD185749 - Sequence 166773 from Patent EP1572962. JD368367 - Sequence 349391 from Patent EP1572962. JD061531 - Sequence 42555 from Patent EP1572962. JD284265 - Sequence 265289 from Patent EP1572962. JD507061 - Sequence 488085 from Patent EP1572962. JD268118 - Sequence 249142 from Patent EP1572962. JD280130 - Sequence 261154 from Patent EP1572962. JD280131 - Sequence 261155 from Patent EP1572962. DQ185035 - Homo sapiens Wolf-Hirschhorn syndrome candidate 1 (WHSC1) mRNA, 3' UTR. JD080773 - Sequence 61797 from Patent EP1572962. BX647495 - Homo sapiens mRNA; cDNA DKFZp686B10142 (from clone DKFZp686B10142). JD316100 - Sequence 297124 from Patent EP1572962. JD395569 - Sequence 376593 from Patent EP1572962. JD423195 - Sequence 404219 from Patent EP1572962. JD075389 - Sequence 56413 from Patent EP1572962. JD045795 - Sequence 26819 from Patent EP1572962. JD142650 - Sequence 123674 from Patent EP1572962. JD491615 - Sequence 472639 from Patent EP1572962. JD058257 - Sequence 39281 from Patent EP1572962. JD387709 - Sequence 368733 from Patent EP1572962. JD155588 - Sequence 136612 from Patent EP1572962. JD059863 - Sequence 40887 from Patent EP1572962. JD222795 - Sequence 203819 from Patent EP1572962. JD406603 - Sequence 387627 from Patent EP1572962. LF206814 - JP 2014500723-A/14317: Polycomb-Associated Non-Coding RNAs. LF358183 - JP 2014500723-A/165686: Polycomb-Associated Non-Coding RNAs. JD468775 - Sequence 449799 from Patent EP1572962. JD335992 - Sequence 317016 from Patent EP1572962. JD391613 - Sequence 372637 from Patent EP1572962. JD168800 - Sequence 149824 from Patent EP1572962. JD386982 - Sequence 368006 from Patent EP1572962. MA442391 - JP 2018138019-A/14317: Polycomb-Associated Non-Coding RNAs. MA593760 - JP 2018138019-A/165686: Polycomb-Associated Non-Coding RNAs. JD096570 - Sequence 77594 from Patent EP1572962. JD037928 - Sequence 18952 from Patent EP1572962. JD103828 - Sequence 84852 from Patent EP1572962. JD184668 - Sequence 165692 from Patent EP1572962. JD075963 - Sequence 56987 from Patent EP1572962. JD136531 - Sequence 117555 from Patent EP1572962. JD227200 - Sequence 208224 from Patent EP1572962. JD274425 - Sequence 255449 from Patent EP1572962. JD556262 - Sequence 537286 from Patent EP1572962. JD123138 - Sequence 104162 from Patent EP1572962. JD217618 - Sequence 198642 from Patent EP1572962. JD103943 - Sequence 84967 from Patent EP1572962. JD334832 - Sequence 315856 from Patent EP1572962. JD485153 - Sequence 466177 from Patent EP1572962. JD423255 - Sequence 404279 from Patent EP1572962. JD470475 - Sequence 451499 from Patent EP1572962. JD370512 - Sequence 351536 from Patent EP1572962. JD406212 - Sequence 387236 from Patent EP1572962. JD179650 - Sequence 160674 from Patent EP1572962. JD297492 - Sequence 278516 from Patent EP1572962. JD150306 - Sequence 131330 from Patent EP1572962. JD289078 - Sequence 270102 from Patent EP1572962. JD221103 - Sequence 202127 from Patent EP1572962. JD273378 - Sequence 254402 from Patent EP1572962. JD107147 - Sequence 88171 from Patent EP1572962. JD231458 - Sequence 212482 from Patent EP1572962. JD369193 - Sequence 350217 from Patent EP1572962. JD135222 - Sequence 116246 from Patent EP1572962. JD472048 - Sequence 453072 from Patent EP1572962. JD549580 - Sequence 530604 from Patent EP1572962. JD485462 - Sequence 466486 from Patent EP1572962. JD565046 - Sequence 546070 from Patent EP1572962. JD425126 - Sequence 406150 from Patent EP1572962. JD363645 - Sequence 344669 from Patent EP1572962. JD308694 - Sequence 289718 from Patent EP1572962. JD312853 - Sequence 293877 from Patent EP1572962. JD284460 - Sequence 265484 from Patent EP1572962. JD503812 - Sequence 484836 from Patent EP1572962. JD445895 - Sequence 426919 from Patent EP1572962. JD554287 - Sequence 535311 from Patent EP1572962. JD385387 - Sequence 366411 from Patent EP1572962. JD214942 - Sequence 195966 from Patent EP1572962. JD039991 - Sequence 21015 from Patent EP1572962. JD536088 - Sequence 517112 from Patent EP1572962. JD264460 - Sequence 245484 from Patent EP1572962. JD497965 - Sequence 478989 from Patent EP1572962. JD532866 - Sequence 513890 from Patent EP1572962. JD154788 - Sequence 135812 from Patent EP1572962. JD111603 - Sequence 92627 from Patent EP1572962. JD521328 - Sequence 502352 from Patent EP1572962. JD126120 - Sequence 107144 from Patent EP1572962. JD251638 - Sequence 232662 from Patent EP1572962. JD543818 - Sequence 524842 from Patent EP1572962. JD438573 - Sequence 419597 from Patent EP1572962. JD375759 - Sequence 356783 from Patent EP1572962. JD098311 - Sequence 79335 from Patent EP1572962. LF358184 - JP 2014500723-A/165687: Polycomb-Associated Non-Coding RNAs. MA593761 - JP 2018138019-A/165687: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein O96028 (Reactome details) participates in the following event(s):
R-HSA-5682967 WHSC1 binds DNA DSBs R-HSA-5684071 RNF4 ubiquitinates MDC1 R-HSA-5693599 Association of Ku heterodimer with ends of DNA double-strand break R-HSA-5682983 ATM phosphorylates WHSC1 R-HSA-5682992 KDM4A,B bind H4K20Me2 R-HSA-5682965 WHSC1 dimethylates histone H4 on lysine K21 at DSBs R-HSA-4827383 WHSC1 (KMT3G), NSD1 (KMT3B), SMYD2 (KMT3C) methylate lysine-37 of histone H3 (H3K36) R-HSA-5638157 WHSC1 (KMT3G), NSD1 (KMT3B), SMYD2 (KMT3C), ASH1L methylate methyl-lysine-37 of histone H3 (H3K36) R-HSA-5638333 WHSC1 (KMT3G) methylates lysine-28 of histone H3 (H3K27) R-HSA-5649800 WHSC1L1 (KMT3F) methylates methyl-lysine-28 of histone H3 (H3K27) R-HSA-5649802 WHSC1L1 (KMT3F) methylates dimethyl-lysine-28 of histone H3 (H3K27) R-HSA-5682588 RNF8 binds phosphorylated MDC1 at DNA DSBs R-HSA-5693566 TP53BP1 associates with H4K20Me2 at DNA DSBs R-HSA-5683077 RNF8 and RNF168 ubiquitinate KDM4A,B R-HSA-5682586 HERC2 and PIAS4 are recruited to DNA DSBs R-HSA-5682629 HERC2 facilitates UBE2N:UBE2V2 binding to RNF8 R-HSA-5682607 PIAS4 SUMOylates HERC2 with SUMO1 at DNA DSBs R-HSA-5682863 RNF168 binds DNA DSBs R-HSA-5682858 RNF8 and RNF168 ubiquitinate H2AFX R-HSA-5683384 UIMC1 and FAM175A bind DNA DSBs R-HSA-5683405 PPP5C dephosphorylates TP53BP1 R-HSA-5683425 ATM phosphorylates TP53BP1 at DNA DSBs R-HSA-5682598 ATM phosphorylates HERC2 R-HSA-5693551 Phosphorylation of BRCA1-A complex at multiple sites by ATM R-HSA-5683385 Formation of BRCA1-A complex at DNA DSBs R-HSA-5683735 CHEK2 is recruited to DNA DSBs R-HSA-5683801 CHEK2 phosphorylates BRCA1 R-HSA-69891 Phosphorylation and activation of CHEK2 by ATM R-HSA-5684052 PIAS4 SUMOylates MDC1 R-HSA-5686685 RIF1 and PAX1IP bind TP53BP1 at DNA DSBs R-HSA-5686900 TP53BP1 recruits DCLRE1C to ATM R-HSA-5686704 Activated ATM phosphorylates DCLRE1C R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks R-HSA-5693607 Processing of DNA double-strand break ends R-HSA-5693571 Nonhomologous End-Joining (NHEJ) R-HSA-5693606 DNA Double Strand Break Response R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-3214841 PKMTs methylate histone lysines R-HSA-5693538 Homology Directed Repair R-HSA-73894 DNA Repair R-HSA-3247509 Chromatin modifying enzymes R-HSA-4839726 Chromatin organization R-HSA-69473 G2/M DNA damage checkpoint R-HSA-69481 G2/M Checkpoints R-HSA-69620 Cell Cycle Checkpoints R-HSA-1640170 Cell Cycle
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
