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IUBMB CommentsThis entry describes enzymes that successively methylate the L-lysine27 residue of histone H3 (H3K27) twice, ultimately generating a dimethylated form. These modifications influence the binding of chromatin-associated proteins. The human NSD3 protein also catalyses the activity of EC 2.1.1.370, [histone H3]-lysine4 N-dimethyltransferase. cf. EC 2.1.1.369, [histone H3]-lysine27 N-methyltransferase, and EC 2.1.1.356, [histone H3]-lysine27 N-trimethyltransferase.
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S-adenosyl-L-methionine + a [histone H3]-L-lysine27
S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine27
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S-adenosyl-L-methionine + a [histone H3]-N6-methyl-L-lysine27
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine27
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S-adenosyl-L-methionine + [histone H3]-L-lysine27
S-adenosyl-L-homocysteine + [histone H3]-N6-methyl-L-lysine27
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S-adenosyl-L-methionine + [histone H3]-N6-methyl-L-lysine27
S-adenosyl-L-homocysteine + [histone H3]-N6,N6-dimethyl-L-lysine27
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Nsd3 is specific for the histones H3K4 and H3K27 residues
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enzyme shows versatility in substrate recognition. In a pan-methylation assay of histone H3, H3K4me3 and H3K27me3 species are preferably detected rather than me1 and me2 species, and H3K79-me1 and -me2 species are favored against me3 species. NSD3 shows significant di-/tri-methylation of histone H4K20
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SET1 methylates both K9 and less efficiently K27 of histone H3 in vitro, reactions of EC 2.1.1.368 and 2.1.1.371, respectively
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Breast Neoplasms
The NSD3L histone methyltransferase regulates cell cycle and cell invasion in breast cancer cells.
Carcinogenesis
The histone methyltransferase Wolf-Hirschhorn syndrome candidate 1-like 1 (WHSC1L1) is involved in human carcinogenesis.
Neoplasms
The NSD3L histone methyltransferase regulates cell cycle and cell invasion in breast cancer cells.
Wolf-Hirschhorn Syndrome
Identification of miR-2400 gene as a novel regulator in skeletal muscle satellite cells proliferation by targeting MYOG gene.
Wolf-Hirschhorn Syndrome
The histone methyltransferase Wolf-Hirschhorn syndrome candidate 1-like 1 (WHSC1L1) is involved in human carcinogenesis.
Wolf-Hirschhorn Syndrome
Wolf-Hirschhorn syndrome candidate 1-like 1 epigenetically regulates nephrin gene expression.
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physiological function
Nsd3 dimethylates H3K4 and additionally di-, and tri-methylates histones H3K27. Overexpression of Nsd3 represses transcription of the SV40 promoter
physiological function
ectopic expression of SET1 increases the amount of dimethylated H3K9 and induces chromosome-segregation defects in tobacco BY2 cells. The histone methyltransferase activity, the association with specific chromatin regions and with condensed chromosomes, and the cellular effects largely depend on the C-terminal region including the SET domain of the protein. The N-terminal part of SET1 is capable of targeting the green fluorescent protein to interphase chromatin. SET1 binds LHP1, the Arabidopsis homolog of animal heterochromatin protein 1, and LHP1 colocalizes with heterochromatin containing high amounts of dimethylated H3K9
physiological function
noncatalytic splice variant NSD3S has with oncogenic activity and appears to bind, stabilize, and activate the transcriptional activity of trancription factor MYC. NSD3S binds to MYC and reduces the association of F-box and WD repeat domain containing FBXW7 with MYC, which results in suppression of FBXW7-mediated proteasomal degradation of MYC and an increase in MYC protein half-life. A 15-amino acid peptide of NSD3S mediates MYC binding
physiological function
siRNA directed depletion of NSD3L identified NSD3L regulated genes linked to cellular signaling pathways such as cell growth, cell cycle, cell motility, transcription, and apoptosis. Up-regulated genes are the cell cycle regulators E2F2 and Arl2. NSD3L depletion results in an increase in the number of cells in the S and G2/M cell cycle phases. NSD3L depletion increases the invasiveness of MDA-MB-231 breast cancer cells
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synthesis
expression of NSDs via tagging with a human influenza hemagglutinin tag greatly improves the quality of the recombinant NSDs, resulting in more than 95% pure, stable, and active NSD-hemagglutinins, with an increase in production yield up to 22.4fold and up to 6.25 mg/l from LB Escherichia coli culture, and without further purification
medicine
Nsd3 expression is increased in both acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL) patients
medicine
NSD3 expression is reduced by isoproterenol stimuli both in vitro and in vivo. Overexpression of NSD3 attenuates isoproterenol-induced cardiomyocyte hypertrophy. Isoproterenol treatment decreases H3K27me2/3 modifications on the atrial natriuretic factor promoter by suppressing NSD3 and inhibits the association between NSD3 and bromodomain-containing protein BRD4, thus suppressing the BRD4-mediated H3K27ac modifications, which ultimately promote atrial natriuretic factor transcription and cardiomyocyte hypertrophy
medicine
silencing of NSD3 in osteosarcoma results in a marked decrease in the number of viable cancer cells, accompanied by increases in the cell population at the G2/M phase and the number of apoptotic cells. NSD3 negatively regulates a number of genes that are involved in the process of negative regulation of signal transduction as well as negative regulation of signaling and cell communication
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Kim, S.M.; Kee, H.J.; Eom, G.H.; Choe, N.W.; Kim, J.Y.; Kim, Y.S.; Kim, S.K.; Kook, H.; Kook, H.; Seo, S.B.
Characterization of a novel WHSC1-associated SET domain protein with H3K4 and H3K27 methyltransferase activity
Biochem. Biophys. Res. Commun.
345
318-323
2006
Homo sapiens (Q9BZ95)
brenda
Yu, Y.; Dong, A.; Shen, W.H
Molecular characterization of the tobacco SET domain protein NtSET1 unravels its role in histone methylation, chromatin binding, and segregation
Plant J.
40
699-711
2004
Nicotiana tabacum (Q93YF5)
brenda
Zhou, Z.; Thomsen, R.; Kahns, S.; Nielsen, A.
The NSD3L histone methyltransferase regulates cell cycle and cell invasion in breast cancer cells
Biochem. Biophys. Res. Commun.
398
565-570
2010
Homo sapiens (Q9BZ95)
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brenda
Li, Y.; Ng, H.; Ngo, A.; Liu, S.; Tan, Y.; Kwek, P.; Hung, A.; Joy, J.; Hill, J.; Keller, T.; Kang, C.
Backbone resonance assignments for the SET domain of human methyltransferase NSD3 in complex with its cofactor
Biomol. NMR Assign.
11
225-229
2017
Homo sapiens (Q9BZ95)
brenda
Morishita, M.; Mevius, D.; Di Luccio, E.
In vitro histone lysine methylation by NSD1, NSD2/MMSET/WHSC1 and NSD3/WHSC1L
BMC Struct. Biol.
14
25
2014
Homo sapiens (Q9BZ95)
brenda
Chen, K.; Jian, D.; Zhao, L.; Zang, X.; Song, W.; Ma, J.; Jia, Z.; Wang, X.; Gao, C.
Protective effect of histone methyltransferase NSD3 on ISO-induced cardiac hypertrophy
FEBS Lett.
593
2556-2565
2019
Homo sapiens (Q9BZ95)
brenda
Gonzalez-Pecchi, V.; Kwan, A.; Doyle, S.; Ivanov, A.; Du, Y.; Fu, H.
NSD3S stabilizes MYC through hindering its interaction with FBXW7
J. Mol. Cell Biol.
12
438-447
2020
Homo sapiens (Q9BZ95)
brenda
Liu, Z.; Piao, L.; Zhuang, M.; Qiu, X.; Xu, X.; Zhang, D.; Liu, M.; Ren, D.
Silencing of histone methyltransferase NSD3 reduces cell viability in osteosarcoma with induction of apoptosis
Oncol. Rep.
38
2796-2802
2017
Homo sapiens (Q9BZ95)
brenda
Shen, Y.; Morishita, M.; di Luccio, E.
High yield recombinant expression and purification of oncogenic NSD1, NSD2, and NSD3 with human influenza hemagglutinin tag
Protein Expr. Purif.
166
105506
2020
Homo sapiens (Q9BZ95)
brenda