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Information on EC 2.1.1.354 - [histone H3]-lysine4 N-trimethyltransferase and Organism(s) Mus musculus and UniProt Accession Q6PDK2

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IUBMB Comments
This entry describes several enzymes that successively methylate the L-lysine4 residue of histone H3 (H3K4), ultimately generating a trimethylated form. These modifications influence the binding of chromatin-associated proteins. In most cases the trimethylation of this position is associated with gene activation. EC 2.1.1.364, [histone H3]-lysine4 N-methyltransferase, describes enzymes that can catalyse only monomethylation of this substrate (the first sub-reaction of this entry); EC 2.1.1.370, [histone H3]-lysine4 N-dimethyltransferase, describes enzymes that catalyse only dimethylation of this substrate (the first two sub-reactions of this entry)
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This record set is specific for:
Mus musculus
UNIPROT: Q6PDK2
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The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
compass, dot1l, smyd3, kmt2d, prdm9, kmt2a, smyd2, kmt2c, ash2l, setd1a, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H3K4 methyltransferase
-
Ash1L
-
-
-
-
H3K4 methyltransferase
-
-
H3K4 trimethyltransferase
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histone H3 lysine 4 methyltransferase activity
-
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histone H3 lysine 4 trimethyltransferase
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histone H3, lysine 4 methyltransferase
-
-
histone H3-lysine-4 methyltransferase
-
-
hybrid sterility protein 1
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KMT2A
KMT2B
KMT2C
KMT2D
KMT2E
-
-
-
-
KMT2F
KMT2G
KMT2H
-
-
-
-
KMT3C
-
-
-
-
KMT3E
-
-
-
-
MLL5
-
-
-
-
PRDM7
-
-
-
-
Prdm9
set1 histone H3-Lys4 methyltransferase complex
-
-
Setd1A
Setd1B
-
-
SMYD1
-
-
-
-
Smyd2
-
-
-
-
Smyd3
-
-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:[histone H3]-L-lysine4 N6-methyltransferase
This entry describes several enzymes that successively methylate the L-lysine4 residue of histone H3 (H3K4), ultimately generating a trimethylated form. These modifications influence the binding of chromatin-associated proteins. In most cases the trimethylation of this position is associated with gene activation. EC 2.1.1.364, [histone H3]-lysine4 N-methyltransferase, describes enzymes that can catalyse only monomethylation of this substrate (the first sub-reaction of this entry); EC 2.1.1.370, [histone H3]-lysine4 N-dimethyltransferase, describes enzymes that catalyse only dimethylation of this substrate (the first two sub-reactions of this entry)
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3 S-adenosyl-L-methionine + a [histone H3]-L-lysine4
3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine4
show the reaction diagram
overall reaction
-
-
?
S-adenosyl-L-methionine + a [histone H3]-L-lysine4
S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine4
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-N6,N6-dimethyl-L-lysine4
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine4
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-N6-methyl-L-lysine4
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine4
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
S-adenosyl-L-homocysteine + N-methylated histone H3(K4)
show the reaction diagram
-
-
-
?
3 S-adenosyl-L-methionine + a [histone H3]-L-lysine4
3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine4
show the reaction diagram
-
overall reaction
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
3 S-adenosyl-L-methionine + a [histone H3]-L-lysine4
3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine4
show the reaction diagram
overall reaction
-
-
?
S-adenosyl-L-methionine + a [histone H3]-L-lysine4
S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine4
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-N6,N6-dimethyl-L-lysine4
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine4
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-N6-methyl-L-lysine4
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine4
show the reaction diagram
-
-
-
?
3 S-adenosyl-L-methionine + a [histone H3]-L-lysine4
3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine4
show the reaction diagram
-
overall reaction
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
CXXC finger protein 1
-
restricts the activity of the Set1 histone methyltransferase complex
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
lacking CXXC finger protein 1, cells show elevated levels of methylated histone H3-Lys4 and reduced levels of methylated histone H3-Lys9
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
enzyme knockout spontaneously induces medulloblastoma. Enzyme loss upregulates oncogenic Ras and Notch pathways while downregulating neuronal gene expression programs. Enzyme loss downregulates tumor suppressor genes (e.g., Dnmt3a and Bcl6). Enzyme loss increases cell proliferation in the cerebellum but negatively impacts cerebellar neurons
metabolism
the enzyme indirectly downregulates Ras activators by enhancing DNMT3A-mediated DNA methylation. The enzyme indirectly antagonizes Notch pathway components (e.g., Hes1 and Jag1) by upregulating SIRT1/BCL6-mediated H4K16 deacetylation
physiological function
isoform KMT2D functions as a bona fide tumor suppressor and its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center involution and impedes B cell differentiation and class switch recombination. KMT2D affects methylation of lysine 4 on histone H3 (H3K4) and expression of a set of genes, including those in the CD40, JAK-STAT, Toll-like receptor and B cell receptor signaling pathways. Other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3 and TNFRSF14
malfunction
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
KMT2D_MOUSE
5588
0
600245
Swiss-Prot
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed HEK-293 cells
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lee, J.H.; Skalnik, D.G.
CpG-binding protein (CXXC finger protein 1) is a component of the mammalian Set1 histone H3-Lys4 methyltransferase complex, the analogue of the yeast Set1/COMPASS complex
J. Biol. Chem.
280
41725-41731
2005
Mus musculus, Homo sapiens (O15047), Homo sapiens
Manually annotated by BRENDA team
Kim, D.H.; Lee, J.; Lee, B.; Lee, J.W.
ASCOM controls farnesoid X receptor transactivation through its associated histone H3 lysine 4 methyltransferase activity
Mol. Endocrinol.
23
1556-1562
2009
Mus musculus
Manually annotated by BRENDA team
Lee, J.; Kim, D.H.; Lee, S.; Yang, Q.H.; Lee, D.K.; Lee, S.K.; Roeder, R.G.; Lee, J.W.
A tumor suppressive coactivator complex of p53 containing ASC-2 and histone H3-lysine-4 methyltransferase MLL3 or its paralogue MLL4
Proc. Natl. Acad. Sci. USA
106
8513-8518
2009
Mus musculus
Manually annotated by BRENDA team
Mihola, O.; Trachtulec, Z.; Vlcek, C.; Schimenti, J.; Forejt, J.
A mouse speciation gene encodes a meiotic histone H3 methyltransferase
Science
323
373-375
2009
Mus musculus (C4MLH8), Mus musculus
Manually annotated by BRENDA team
Ortega-Molina, A.; Boss, I.W.; Canela, A.; Pan, H.; Jiang, Y.; Zhao, C.; Jiang, M.; Hu, D.; Agirre, X.; Niesvizky, I.; Lee, J.E.; Chen, H.T.; Ennishi, D.; Scott, D.W.; Mottok, A.; Hother, C.; Liu, S.; Cao, X.J.; Tam, W.; Shaknovich, R.; Garcia, B.A.; Gascoyne, R.D.; Ge, K.; Shilatifard, A.; Elemento, O.; Nussenzweig, A.; Melnick, A.M.; Wendel, H.G.
The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development
Nat. Med.
21
1199-1208
2015
Mus musculus (Q6PDK2)
Manually annotated by BRENDA team
Yang, W.; Ernst, P.
Distinct functions of H3K4 methyltransferases in normal and malignant hematopoiesis
Curr. Opin. Hematol.
24
322-328
2017
Mus musculus
Manually annotated by BRENDA team
Dhar, S.S.; Zhao, D.; Lin, T.; Gu, B.; Pal, K.; Wu, S.J.; Alam, H.; Lv, J.; Yun, K.; Gopalakrishnan, V.; Flores, E.R.; Northcott, P.A.; Rajaram, V.; Li, W.; Shilatifard, A.; Sillitoe, R.V.; Chen, K.; Lee, M.G.
MLL4 is required to maintain broad H3K4me3 peaks and super-enhancers at tumor suppressor genes
Mol. Cell
70
825-841.e6
2018
Mus musculus (Q6PDK2)
Manually annotated by BRENDA team