DegronMD - O96028(NSD2)

FUNCTION: Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2) (PubMed:27571355, PubMed:22099308, PubMed:19808676, PubMed:29728617). 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). {ECO:0000250|UniProtKB:Q8BVE8, ECO:0000269|PubMed:16115125, ECO:0000269|PubMed:19808676, ECO:0000269|PubMed:22099308, ECO:0000269|PubMed:27571355, ECO:0000269|PubMed:29728617}.; FUNCTION: [Isoform 1]: Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2). {ECO:0000269|PubMed:22099308}.; FUNCTION: [Isoform 4]: Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2) (PubMed:22099308). Methylation of histone H3 at 'Lys-27' is controversial (PubMed:18172012, PubMed:22099308). Mono-, di- or tri-methylates histone H3 at 'Lys-27' (H3K27me, H3K27me2 and H3K27me3) (PubMed:18172012). Does not methylate histone H3 at 'Lys-27' (PubMed:22099308). May act as a transcription regulator that binds DNA and suppresses IL5 transcription through HDAC recruitment (PubMed:11152655, PubMed:18172012). {ECO:0000269|PubMed:11152655, ECO:0000269|PubMed:18172012, ECO:0000269|PubMed:22099308}. View more >>

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GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.T551M	SIDM00926	Non-Small Cell Lung Carcinoma	GDSC	EAEDTPRK	DEG_SCF_SKP2-CKS1_1	540:547	Mutation rewiring degron network	0.2222
p.D560E	SIDM00845	Burkitt's Lymphoma	GDSC	ARTSS	DEG_SPOP_SBC_1	567:571	Mutation rewiring degron network	0.1389
p.D560H	SIDM01233	Colorectal Carcinoma	GDSC	ARTSS	DEG_SPOP_SBC_1	567:571	Mutation rewiring degron network	0.1389
p.D560H	C2BBe1	large intestine	COSMIC	ARTSS	DEG_SPOP_SBC_1	567:571	Mutation rewiring degron network	0.1389
p.K998E	SIDM00214	Colorectal Carcinoma	GDSC	PPPY	ITCH	988:991	Mutation substituting flanking lysine	0.25
p.K998E	SNU-407	large intestine	COSMIC	PPPY	ITCH	988:991	Mutation substituting flanking lysine	0.25
p.R986H	SIDM01031	Esophageal Squamous Cell Carcinoma	GDSC	PPPY	ITCH	988:991	Mutation rewiring degron network	0.2778
p.R986H	KYSE-150	oesophagus	COSMIC	PPPY	ITCH	988:991	Mutation rewiring degron network	0.2778
p.K573T	SIDM01611	Endometrial Carcinoma	GDSC	ARTSS	DEG_SPOP_SBC_1	567:571	Mutation rewiring degron network	0.2778
p.M575I	SIDM01519	Head and Neck Carcinoma	GDSC	ARTSS	DEG_SPOP_SBC_1	567:571	Mutation rewiring degron network	0.2222
p.R575Q	ESS-1	endometrium	COSMIC	ARTSS	DEG_SPOP_SBC_1	567:571	Mutation rewiring degron network	0.2222
p.L109I	NCI-H1355	lung	COSMIC	IGTPPNT	DEG_SCF_FBW7_1	108:114	Mutation altering degron motif	0.7174

DegronMD: protein-targeted degradation, mutation and drug response to degrons

NSD2

UniProt ID: O96028

Entrez ID: 7468

Protein name: Histone-lysine N-methyltransferase NSD2 (EC 2.1.1.357) (Multiple myeloma SET domain-containing protein) (MMSET) (Nuclear SET domain-containing protein 2) (Protein trithorax-5) (Wolf-Hirschhorn syndrome candidate 1 protein)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for NSD2 in