Information on EC 2.1.1.43 - histone-lysine N-methyltransferase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY
2.1.1.43
-
RECOMMENDED NAME
GeneOntology No.
histone-lysine N-methyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
catalytic mechanism
-
S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
substrate and inhibitor binding site, amino acid sequence comparison
-
S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
amino acid sequence comparison
-
S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
amino acid sequence comparison
-
S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
enzyme is encoded on genes containing the SET-domain sequence, substrate specificity is connected to SET sequence
-
S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
enzyme is encoded on genes containing the SET-domain sequence, substrate specificity is connected to SET sequence
-
S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
enzyme is encoded on genes containing the SET-domain sequence, substrate specificity is connected to SET sequence
-
S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
enzyme is encoded on genes containing the SET-domain sequence, substrate specificity is connected to SET sequence
-
S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
enzyme is encoded on genes containing the SET-domain sequence, substrate specificity is connected to SET sequence
-
S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
enzyme is encoded on genes containing the SET-domain sequence, substrate specificity is connected to SET sequence
-
S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
enzyme is encoded on genes containing the SET-domain sequence, substrate specificity is connected to SET sequence
-
S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
SET structure
-
S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
formation of epsilon-N-dimethyllysine in a 2-step process via epsilon-N-monomethyl-lysine
-
S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
H3-Lys9 methylation is catalyzed by the Suv39h family proteins
-
S-adenosyl-L-methionine + histone L-lysine = S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
H3-Lys9 methylation is catalyzed by the Suv39h family proteins
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
methyl group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
carnitine metabolism
-
-
Lysine degradation
-
-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:histone-L-lysine N6-methyltransferase
One of a group of enzymes methylating proteins; see also EC 2.1.1.59, [cytochrome-c]-lysine N-methyltransferase and EC 2.1.1.60, calmodulin-lysine N-methyltransferase.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
histone H1-specific S-adenosylmethionine:protein-lysine N-methyltransferase
-
-
-
-
methyltransferase, protein (lysine)
-
-
-
-
protein (lysine) methyltransferase
-
-
-
-
protein methylase 3
-
-
-
-
protein methylase III
-
-
-
-
protein methyltransferase II
-
-
-
-
protein-lysine N-methyltransferase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9055-08-7
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
ecotype Col-0
-
-
Manually annotated by BRENDA team
calf
-
-
Manually annotated by BRENDA team
strain CAI12
-
-
Manually annotated by BRENDA team
Candida albicans CAI12
strain CAI12
-
-
Manually annotated by BRENDA team
SET8 sequence
-
-
Manually annotated by BRENDA team
vector insertion lines, GS13895 and GS17621
-
-
Manually annotated by BRENDA team
2 enzyme forms: VA and VB
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
HeLa cells; SET8 sequence
SwissProt
Manually annotated by BRENDA team
NSD2
UniProt
Manually annotated by BRENDA team
SET9, also called SET7
-
-
Manually annotated by BRENDA team
SETD2
UniProt
Manually annotated by BRENDA team
G9a histone methyltransferase
-
-
Manually annotated by BRENDA team
DIM-5 protein
-
-
Manually annotated by BRENDA team
strain 3D7
-
-
Manually annotated by BRENDA team
similar enzyme with low activity towards calf thymus histone but high activity towards ribosomal protein
-
-
Manually annotated by BRENDA team
wild-type strain ATCC MYA-2089 and mutant strain ATCC MYA-1924
-
-
Manually annotated by BRENDA team
strain Lister 427
-
-
Manually annotated by BRENDA team
Trypanosoma brucei Lister 427
strain Lister 427
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-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
ashh2 mutants are defective in ovule and embryo sac development, mutation in ASHH2 leads to substantial changes in inflorescence gene expression
malfunction
-
Dot1L-deficient embryonic stem cells show global loss of histone H3(K79) methylation as well as reduced levels of heterochromatic marks (histone H3(K9) di-methylation and histone H4(K20) tri-methylation) at centromeres and telomeres, Dot1L deficiency results in embryonic lethality
malfunction
-
embryonic stem cells lacking the H3K9 HMTase G9a show a significant reduction in DNA methylation of retrotransposons, major satellite repeats and densely methylated CpG-rich promoters
malfunction
-
failure to recruit Rad9 or Dot1 to histone H3 leads to an increase in Mec1 activation
malfunction
-
G9a deficiency causes loss of imprinting in the placenta but not the embryo
malfunction
-
knockdown of G9a or SETDB1 throughout development with an ACT5C-GAL4 driver produces organism- level defects only in the case of dSETDB1
malfunction
-
lymphocyte development is unperturbed in G9a-deficient mice, G9a deficiency results in reduced usage of Iglambda L chains and a corresponding inhibition of Iglambda gene assembly in bone marrow precursors
malfunction
C4MLH8
Prdm9-null mice show arrest of spermatogenesis and oogenesis at pachynema, impairment of double-strand break repair, chromosome asynapsis, and disrupted sex-body formation
malfunction
-
SET7/9 deficiency does not affect p65 DNA binding as assessed by electrophoretic mobility shift assays, S100b-induced gene expression is decreased by SET7/9 knockdown
malfunction
-
targeted inactivation of MLL3 H3K4 methyltransferase activity in the mouse causes ureter epithelial tumors, about 50% of MLL-deficient mice display unusual hyperproliferation and tumors in the innermost layer of ureter cells located close to the renal pelvis
malfunction
-
the SMYD2 gain of function leads to an increase in H3K4 methylation in vivo, whereas no observable levels of H3K36 are detected, the SMYD2 gain of function is correlated with the upregulation of 37 and down-regulation of four genes, the majority of which are involved in the cell cycle, chromatin remodeling, and transcriptional regulation, up-regulation of TACC2 by SMYD2 occurs as a result of SMYD2 binding to the TACC2 promoter where it methylates histone H3(K4)
malfunction
-
transcriptionally silent telomeric variant surface glycoproteins become partially derepressed when DOT1B is deleted, whereas nontelomeric loci are unaffected
malfunction
-
ASH1 knockdown causes reduced expression of Hox genes. Knockdown of ASH1 in K-562 cells in vitro causes increased expression of epsilon-globin gene and reduced expression of myelomonocytic markers GPIIb and GPIIIa, whereas knockdown of ASH1 in haematopoietic stem cells in vivo results in decreased number of macrophages and granulocytes
malfunction
-
deletion of G9A or GLP is lethal to mouse embryos
malfunction
-
depletion of histone lysine demethylase JARID1a reduces Per promoter histone acetylation, dampens expression of canonical circadian genes, and shortens the period of circadian rhythms
malfunction
-
genetic knockdown of G9a inhibits cancer cell growth
malfunction
-
histone H3(K4) di- and trimethylations are significantly reduced in dSet1 mutants during late larval und post-larval stages
malfunction
-
homozygous disruption of Hypb impairs histone H3(K36) trimethylation but not mono- or dimethylation, and resulted in embryonic lethality at E10.5-E11.5. Severe vascular defects are observed in the Hypb-deficient embryo, yolk sac, and placenta
malfunction
-
human endothelial cells with siRNA-mediated suppression of HYPB, show defects in cell migration, tubule formation, and invasion during vessel formation
malfunction
-
inhibition of G9a/GLP in the entorhinal cortex (EC), but not in the hippocampus, enhances contextual fear conditioning relative to control animals. Downregulation of G9a/GLP activity in the EC enhances histone H3(K9) dimethylation in hippocampus area CA1, resulting in transcriptional silencing of the non-memory permissive gene COMT in the hippocampus
malfunction
-
mutations in enzyme SDG724 are responsible for the late-flowering phenotype of late-flowering long vegetative phase 1 plants
malfunction
-
mutations in the catalytic subunit E(Z) that abolish methyltransferase activity disrupt Polycomb silencing, causing derepression of Polycomb target genes in cells where they are normally silenced. Increased histone H3(K27) trimethylation activity of mutant E(Z)Trm causes the premature accumulation of trimethylated histone H3(K27) in early embryogenesis, predestining initially active Polycomb target genes to silencing once Polycomb silencing is initiated
malfunction
-
reduced expression of the histone lysine demethylase Lid leads to lowered Per expression and no or weak circadian activity
malfunction
Trypanosoma brucei Lister 427
-
transcriptionally silent telomeric variant surface glycoproteins become partially derepressed when DOT1B is deleted, whereas nontelomeric loci are unaffected
-
physiological function
-
DNA methylation of retrotransposons in embryonic stem cells requires the lysine methyltransferase G9a but not its catalytic activity
physiological function
-
Dot1 and Rad9 inhibit single-stranded DNA accumulation at DSBs and uncapped telomeres, Dot1 contributes to checkpoint activation in response to low levels of telomere uncapping but is not essential with high levels of uncapping, Rad9 contributes to DNA damage metabolism because Rad9 inhibits the accumulation of single stranded DNA at uncapped telomeres
physiological function
-
Dot1 is required for efficient sister chromatid recombination, Dot1 promotes DNA double-strand break-induced loading of cohesin onto chromatin
physiological function
-
DOT1B is required to maintain strict variant surface glycoproteins silencing and to ensure rapid transcriptional variant surface glycoproteins switching
physiological function
-
Dot1L and histone H3(K79) methylation play important roles in heterochromatin formation and in embryonic development
physiological function
-
Dpy-30 functions in the endosome to trans-Golgi network transport of cation-independent mannose 6-phosphate receptor, its knockdown results in the enrichment of internalized cation-independent mannose 6-phosphate receptor and recycling endosomes near cell protrusions. Dpy-30 and probably histone H3 lysine 4 methyltransferase play a role in the endosomal transport of specific cargo proteins
physiological function
-
MLL3 and MLL4 function redundantly with farnesoid X receptor transactivation
physiological function
-
NSD2 specifically interacts with the DNA-binding domain of androgen receptor via its HMG domain, and the nuclear translocation of both NSD2 and androgen receptor is enhanced in the presence of ligand, NSD2 protein is recruited to the enhancer region of the PSA gene by androgen receptor in an agonist-enhanced manner, there is a potential role for NSD2 in androgen receptor-mediated transcription implicating NSD2 in prostate carcinogenesis
physiological function
-
PRDM8 repressed the expression of steroidogenic markers, p450c17c and luteinizing hormone receptor, which indicates its regulatory role in mouse testis development and steroidogenesis
physiological function
-
RE-IIBP represses basal transcription via histone deacetylase recruitment, which may be mediated by histone H3(K27) methylation, knockdown of RE-IIBP reduces histone H3-K27 methylation and histone deacetylase occupancy around the interleukin-5 promoter
physiological function
-
SDG8 regulates shoot branching via controlling the methylation states of its target genes
physiological function
Q8WTS6
SET7-mediated methylation stabilizes estrogen receptor alpha and is necessary for the efficient recruitment of estrogen receptor alpha to its target genes, and their transactivation
physiological function
-
SET7/9 may act as a transcriptional cofactor of NF-kappaB p65, SET7/9 may regulate NF-kappaB-dependent genes through modifications of chromatin histone lysine at these specific gene promoters, SET7/9 is recruited to the promoters of inflammatory genes and enhances p65 recruitment to these gene promoters, SET7/9 is not involved in monocyte differentiation but affects monocyte adhesion
physiological function
-
SETDB1 acts to maintain heterochromatin during metamorphosis, at a later stage in development than the reported action of SU(VAR)3-9, depletion of both of these enzymes has less deleterious effect than depletion of one, SETDB1 acts as a heterochromatin maintenance factor that may be required for the persistence of earlier developmental events normally governed by SU(VAR)3-9
physiological function
-
SMYD3 is required for estrogen receptor-mediated transcription, SMYD3 functions as a coactivator of estrogen receptor alpha and potentiates estrogen receptor alpha activity in response to ligand
physiological function
-
Suv4-20 is not required for survival and does not control position-effect variegation
physiological function
-
the gene grappa encoding a histone methyltransferase is required for normal lifespan and stress resistance, its overexpression increases stress resistance in Drosophila, without obvious induction of representative anti-oxidant genes
physiological function
-
the main requirement of ASHH2 is in the sporophyte for proper development or function of ovules and anthers, ASHH2 is required for normal embryo-sac development, anther differentiation, tapetum development and pollen maturation
physiological function
-
ASH1 regulates endogenous Hox gene expression positively and negatively and is required for myelomonocytic differentiation. ASH1 and MLL1 co-operate in Hox promoter activation
physiological function
-
Dot1 and histone H3(K79) methylation are required for global genomic repair in both nucleosomal core regions and internucleosomal linker DNA but the enzyme is entirely dispensable for transcription coupled repair
physiological function
-
Drosophila Set1 is the major histone H3 lysine 4 trimethyltransferase with role in transcription. dSet1-dependent histone H3 lysine 4 trimethylation is responsible for the generation of a chromatin structure at active promoters that ensures optimal polymerase II release into productive elongation
physiological function
-
dSet1 is the main histone H3(K4) di- and tri-methyltransferase throughout Drosophila development. dSet1 interacts with members of a putative Drosophila COMPASS (complex of proteins associated with Set1) which is functionally required for histone H3(K4) methylation
physiological function
-
G9A and GLP silence gene expression through H3K9 methylation, and.[22] In addition, G9A plays a critical role in regulating embryonic stem cell differentiation through silencing the gene that encodes the pluripotency-determining transcription factor Oct3/4. H3K9 dimethylation by G9A is linked to aberrant silencing of tumor-suppressor genes, thereby promoting unchecked cell proliferation. Furthermore, G9A and GLP can methylate Lys373 within the regulatory domain of transcription factor p53, inhibiting its tumor-suppressor activity
physiological function
-
G9a/GLP activity is critical for hippocampus-dependent long-term potentiation initiated in the entorhinal cortex via the perforant pathway, but not the temporoammonic pathway. G9a/GLP histone lysine dimethyltransferase complex activity in the hippocampus and the entorhinal cortex is required for gene activation and silencing during memory consolidation
physiological function
-
histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling
physiological function
-
histone lysine demethylase JARID1a activates CLOCK-BMAL1 and influences the circadian clock
physiological function
-
SDG724 promotes flowering in rice. The enzyme Is required in the MADS50-Ehd1-RFT1 flowering pathway under long-day conditions and promotes the MADS51-Ehd1-Hd3a flowering pathway under short-day conditions
physiological function
-
SETDB1 is mainly responsible for mono- and trimethylation of histone H3 lysine 9 and SU (VAR)3-9 for monomethylation of histone H3 lysine 9 during spermatogenesis. Enzyme form dG9a plays no apparent role for histone H3 lysine 9 methylation during spermatogenesis and spermiogenesis
physiological function
-
SUVR4 is involved in the epigenetic defense mechanism by trimethylating histone H3(K9) to suppress potentially harmful transposon activity
physiological function
Q7SXS7
the enzyme plays roles as an activator of general transcription and inhibits cell viability by inducing caspase-3 activation overexpression
physiological function
-
trxG complexes in Arabidopsis thaliana involve different sets of histone lysine methyltransferases that are engaged in multiple developmental processes
physiological function
F0NBH8
the enzyme Cren7 plays a major role in methylation of the crenarchaeal chromatin protein Cren7
physiological function
-
the enzyme Cren7 plays a major role in methylation of the crenarchaeal chromatin protein Cren7
-
physiological function
Trypanosoma brucei Lister 427
-
DOT1B is required to maintain strict variant surface glycoproteins silencing and to ensure rapid transcriptional variant surface glycoproteins switching
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
biotinyl-MARTKQTARKSTGGKAPRKQ + S-adenosyl-L-methionine
?
show the reaction diagram
-
Dim-5 methylates the histone H3 tail at position Lys9
-
-
-
polylysine + S-adenosylmethionine
S-adenosyl-L-homocysteine + N6-methylpolylysine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + biotin-aminohexanoyl-GSRAHSSHLKSKKGQSTSRH
?
show the reaction diagram
-
100% activity
-
-
?
S-adenosyl-L-methionine + biotin-ARTKQTARKST
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + CDYL1 protein
?
show the reaction diagram
-
target of histone lysine methyltransferase G9a (KMT1C)
-
-
?
S-adenosyl-L-methionine + CSB protein
?
show the reaction diagram
-
target of histone lysine methyltransferase G9a (KMT1C)
-
-
?
S-adenosyl-L-methionine + dimethylated histone H3(K9)
S-adenosyl-L-homocysteine + trimethylated histone H3(K9)
show the reaction diagram
-
the activity on dimethylated histone H3(K9) peptides is several folds lower than when monomethylated histone H3(K9) peptides are used
-
-
?
S-adenosyl-L-methionine + DNA methyltransferase 1
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + estrogen receptor alpha(K302)
?
show the reaction diagram
Q8WTS6
estrogen receptor alpha is directly methylated at lysine-302 by SET-7, a K303R mutation inhibits methylation at K302 in vivo
-
-
?
S-adenosyl-L-methionine + HDAC1 protein
?
show the reaction diagram
-
target of histone lysine methyltransferase G9a (KMT1C)
-
-
?
S-adenosyl-L-methionine + histone (K4)
S-adenosyl-L-homocysteine + methylated histone (K4)
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone 3(K4)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone 3(K79)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H1
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H1.4(K121)
?
show the reaction diagram
-
less than 10% methylation at Lys-34
-
-
?
S-adenosyl-L-methionine + histone H1.4(K26)
?
show the reaction diagram
-
70% methylation at Lys-26, methylation of the K26A mutant of histone H1.4 is strongly reduced but not completely abolished
-
-
?
S-adenosyl-L-methionine + histone H1.4(K34)
?
show the reaction diagram
-
10-15% methylation at Lys-34
-
-
?
S-adenosyl-L-methionine + histone H1.4(K52)
?
show the reaction diagram
-
less than 1% methylation at Lys-34
-
-
?
S-adenosyl-L-methionine + histone H2A
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H2A
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H2B
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H2B
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H2B L-lysine
S-adenosyl-L-homocysteine + histone H2B N6-methyl-L-lysine
show the reaction diagram
-
about 150% activity compared to biotin-aminohexanoyl-GSRAHSSHLKSKKGQSTSRH, H2B is more efficient substrate with 3fold higher specific activity compared to H3
-
-
?
S-adenosyl-L-methionine + histone H3
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3
?
show the reaction diagram
Q8R5A0, Q9CWR2
methylation
-
-
?
S-adenosyl-L-methionine + histone H3
?
show the reaction diagram
-
histone H3 is trimethylated at lysines 9 and 36 as well as dimethylated at lysine 36
-
-
?
S-adenosyl-L-methionine + histone H3 (1-13)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3 (S10phos)
?
show the reaction diagram
-
phosphorylation of the proximal amino acids impairs Lys-9 methylation via impairing enzyme-substrate interaction
-
-
?
S-adenosyl-L-methionine + histone H3 (T11phos)
?
show the reaction diagram
-
phosphorylation of the proximal amino acids impairs Lys-9 methylation via impairing enzyme-substrate interaction
-
-
?
S-adenosyl-L-methionine + histone H3 L-lysine
S-adenosyl-L-homocysteine + histone H3 N6-methyl-L-lysine
show the reaction diagram
-
efficient substrate, about 40% activity compared to biotin-aminohexanoyl-GSRAHSSHLKSKKGQSTSRH
-
-
?
S-adenosyl-L-methionine + histone H3 lysine 36
?
show the reaction diagram
Q8R5A0, Q9CWR2
dimethylation
-
-
?
S-adenosyl-L-methionine + histone H3(K27)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K27)
?
show the reaction diagram
F4YY96
-
-
-
?
S-adenosyl-L-methionine + histone H3(K27)
?
show the reaction diagram
-
di- and trimethylation at histone H3(K27)
-
-
?
S-adenosyl-L-methionine + histone H3(K27)
?
show the reaction diagram
-
RE-IIBP selectively transfers methyl groups to K27 of histone H3
-
-
?
S-adenosyl-L-methionine + histone H3(K27)
?
show the reaction diagram
-
specificity for Lys-27 of histone H3
-
-
?
S-adenosyl-L-methionine + histone H3(K27)
?
show the reaction diagram
-
trimethylation at Lys-27
-
-
?
S-adenosyl-L-methionine + histone H3(K27)
?
show the reaction diagram
-
Drosophila Polycomb Repressive Complex 2 is a lysine methyltransferase that trimethylates histone H3 (K27)
-
-
?
S-adenosyl-L-methionine + histone H3(K27)
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K27A)
?
show the reaction diagram
-
mutation in the unstructured amino-terminal tail of histone H3 does not affect the central globular domain, but reduces the turnover numbers of the substrates
-
-
?
S-adenosyl-L-methionine + histone H3(K36)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K36)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K36)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K36)
?
show the reaction diagram
-
histone H3(K36) di- and trimethylation
-
-
?
S-adenosyl-L-methionine + histone H3(K36)
?
show the reaction diagram
O96028, Q9BYW2
NSD2 shows specific targeting of histone H3 lysine-36, DNA acts as an allosteric effector of NSD2 such that H3K36 becomes the preferred target
-
-
?
S-adenosyl-L-methionine + histone H3(K36)
?
show the reaction diagram
-
SDG724 mediates histone H3(K36)me2/3 deposition at MADS50 and RFT1
-
-
?
S-adenosyl-L-methionine + histone H3(K36)
?
show the reaction diagram
Q7SXS7
the enzyme has histone methyltransferase activity specifically towards mono-, di- and trimethylation of histone H3(K36) residues both in vitro and in vivo
-
-
?
S-adenosyl-L-methionine + histone H3(K36R)
?
show the reaction diagram
-
methylated by GST-mG9a
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
Q8WTS6
-
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
C4MLH8
-
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
-
ASCOM-MLL3 and ASCOM-MLL4 function as redundant but crucial histone H3(K4)-trimethylating coactivator complexes for p53
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
-
di- and trimethylation of histone H3(K4)
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
-
histone H3(K4) dimethylation by Set1 leads to reduced histone acetylation levels near 5' ends of genes
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
-
menin appears to be essential for MLL-mediated histone H3(K4) methylation
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
-
SET7/9 only catalyzes the transfer of one methyl group to the target lysine
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
-
specificity for Lys-4 of histone H3
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
-
target of histone lysine methyltransferases MLL1 (KMT2A) and MLL4 (KMT2D)
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
-
trimethylation of histone H3(K4)
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
-
H3K4 methyltransferase dSet1 is predominantly responsible for histone H3(K4) trimethylation
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
?
show the reaction diagram
Candida albicans CAI12
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K4)
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
enzyme G9A exhibits a modest decrease in catalytic efficiency when assayed with an histone H3(K4)me3 peptide in comparison to an unmodified H3 peptide substrate
-
-
?
S-adenosyl-L-methionine + histone H3(K4A)
?
show the reaction diagram
-
mutation in the unstructured amino-terminal tail of histone H3 does not affect the central globular domain, but reduces the turnover numbers of the substrates
-
-
?
S-adenosyl-L-methionine + histone H3(K76)
?
show the reaction diagram
Trypanosoma brucei, Trypanosoma brucei Lister 427
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K79)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K79)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K79)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K9)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K9)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K9)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K9)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K9)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K9)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H3(K9)
?
show the reaction diagram
-
dimethylation
-
-
?
S-adenosyl-L-methionine + histone H3(K9)
?
show the reaction diagram
-
Dim-5 recognizes R8-G12 of the H3 tail with T11 and G12 being the most important specificity determinants, phosphorylation of H3 tail residues S10 and T11may regulate the activity of Dim-5
-
-
?
S-adenosyl-L-methionine + histone H3(K9)
?
show the reaction diagram
-
dimethylation at Lys-9
-
-
?
S-adenosyl-L-methionine + histone H3(K9)
?
show the reaction diagram
-
p33ING2 recruits histone methyltransferase activity in vitro and in vivo, methylating specifically histone H3, the p33ING2-associated histone methyltransferase shows an increased methylation activity if lysine 9 is methylated
-
-
?
S-adenosyl-L-methionine + histone H3(K9)
?
show the reaction diagram
-
target of histone lysine methyltransferases Suv39H1/2 (KMT1A/B), G9a (KMT1C), Eu-HMTase1 (KMT1D), and SETDB1/ESET (KMT1E)
-
-
?
S-adenosyl-L-methionine + histone H3(K9)
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
PRDM8 specifically methylates H3(K9) of histones
-
-
?
S-adenosyl-L-methionine + histone H3(K9)
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
SETDB1 is mainly responsible for mono- and trimethylation of histone H3 lysine 9 and SU (VAR)3-9 for monomethylation of histone H3 lysine 9 during spermatogenesis
-
-
?
S-adenosyl-L-methionine + histone H3(N)
?
show the reaction diagram
Q9BYW2
methylated by GST-HYPB protein
-
-
?
S-adenosyl-L-methionine + histone H3(N)
?
show the reaction diagram
-
methylated by GST-mG9a
-
-
?
S-adenosyl-L-methionine + histone H3(N27)
?
show the reaction diagram
Q9BYW2
methylated by GST-HYPB protein
-
-
?
S-adenosyl-L-methionine + histone H3(N27)
?
show the reaction diagram
-
methylated by GST-mG9a
-
-
?
S-adenosyl-L-methionine + histone H3(N4)
?
show the reaction diagram
Q9BYW2
methylated by GST-HYPB protein
-
-
?
S-adenosyl-L-methionine + histone H3(N9)
?
show the reaction diagram
Q9BYW2
methylated by GST-HYPB protein
-
-
?
S-adenosyl-L-methionine + histone H3(N9)
?
show the reaction diagram
-
methylated by GST-mG9a
-
-
?
S-adenosyl-L-methionine + histone H3.2 L-lysine
S-adenosyl-L-homocysteine + histone H3.2 N6-methyl-L-lysine
show the reaction diagram
-
about 30% activity compared to biotin-aminohexanoyl-GSRAHSSHLKSKKGQSTSRH
-
-
?
S-adenosyl-L-methionine + histone H4
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H4
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H4 L-lysine
S-adenosyl-L-homocysteine + histone H4 N6-methyl-L-lysine
show the reaction diagram
-
best substrate, H4 is more efficient substrate with 5fold higher specific activity compared to H3, about 240% activity compared to biotin-aminohexanoyl-GSRAHSSHLKSKKGQSTSRH
-
-
?
S-adenosyl-L-methionine + histone H4(K20)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H4(K20)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone H4(K20)
?
show the reaction diagram
-
histone H4 is specifically methylated at lysine-20
-
-
?
S-adenosyl-L-methionine + histone H4(K20)
?
show the reaction diagram
-
specificity for Lys-20 of histone H4
-
-
?
S-adenosyl-L-methionine + histone H4(K20)
?
show the reaction diagram
-
trimethylation
-
-
?
S-adenosyl-L-methionine + histone H4(K20)
?
show the reaction diagram
-
trimethylation at lysine 20 of histone H4
-
-
?
S-adenosyl-L-methionine + histone H4(K20)
?
show the reaction diagram
-
SET8 specifically methylates K20 on the histone H4. Enzyme activity is strongly reduced by the arginine methylation at position R17
-
-
?
S-adenosyl-L-methionine + histone H4(K344)
?
show the reaction diagram
O96028, Q9BYW2
histone H4 lysine-44 is the primary target of NSD2 in the case of octamer substrates, irrespective of the histones being native or recombinant
-
-
?
S-adenosyl-L-methionine + histone K4-acetylK9
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone K4-trimethylK9
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone K4AK9
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
F4YY96
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
a mixture of epsilon-N-mono-, di- and trimethyllysine ratio 4:1:1
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
Lys27 of histone 3
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
lysine-rich histones
a mixture of epsilon-N-mono-, di- and trimethyllysine ratio 4:1:1
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
arginine-rich histones
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
arginine-rich histones
a mixture of epsilon-N-mono-, di- and trimethyllysine ratio 4:1:1
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
Lys36 of histone 3
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
high substrate and methylation site specifity
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
high substrate and methylation site specifity
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
high substrate and methylation site specifity
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
Q9NQR1
high substrate and methylation site specifity
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
Lys9 of histone H3
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
Lys9 of histone H3
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
Lys9 of histone H3
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
highly specific towards histone H1
the 2 enzyme forms VA and VB methylate different sites in the histone H1 molecule with high specificity, VB is more specific than VA, a mixture of epsilon-N-mono-, di- and trimethyllysine ratio 4:1:1
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
Lys4 of histone 3
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
heat-denatured histone
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
Lys20 of histone 4
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
Lys20 of histone 4
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
Q9NQR1
Lys20 of histone 4
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
various types of histones
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
Q9NQR1
Lys20 of histone 4, SET8
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
Lys20 of histone 4, SET8
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
Lys9 of histone 3
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
Q8WTS6
the wild-type SET7/9 is a monomethylase
-
-
?
S-adenosyl-L-methionine + monomethylated histone H3(K9)
S-adenosyl-L-homocysteine + trimethylated histone H3(K9)
show the reaction diagram
-
the SUVR4 product specificity shifts from di- to trimethylation in the presence of free ubiquitin. SUVR4 in vivo specifically converts monomethylated histone H3(K9) to trimethylated histone H3(K9) at transposons and pseudogenes
-
-
?
S-adenosyl-L-methionine + p300/CBP-associated factor
?
show the reaction diagram
-
K78 and K89 are preferentially methylated in full-length p300/CBP-associated factor in vitro
-
-
?
S-adenosyl-L-methionine + p53
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + p53
?
show the reaction diagram
-
about 50% activity compared to biotin-aminohexanoyl-GSRAHSSHLKSKKGQSTSRH
-
-
?
S-adenosyl-L-methionine + p53 (K382)
?
show the reaction diagram
-
SET8 activity is strongly reduced by the arginine methylation at position R379
-
-
?
S-adenosyl-L-methionine + p53(K373)
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + p53(K373)
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + TAF10-K189 peptide
?
show the reaction diagram
Q8WTS6
-
-
-
?
S-adenosyl-L-methionine + transcriptional factor p53
?
show the reaction diagram
-
methylation of transcriptional factor p53 with the sequence LKSKKGQSTY occurs at Lys-4
-
-
?
S-adenosyl-L-methionine + WIZ protein
?
show the reaction diagram
-
target of histone lysine methyltransferase G9a (KMT1C)
-
-
?
S-adenosyl-L-methionine + [primase-subunit-Pri1]-L-lysine
S-adenosyl-L-homocysteine + [primase-subunit-Pri1]-N6-methyl-L-lysine
show the reaction diagram
F0NBH8
-
-
-
?
S-adenosyl-L-methionine + [primase-subunit-Pri2]-L-lysine
S-adenosyl-L-homocysteine + [primase-subunit-Pri2]-N6-methyl-L-lysine
show the reaction diagram
F0NBH8
-
-
-
?
S-adenosyl-L-methionine + [protein Cren7]-L-lysine
S-adenosyl-L-homocysteine + [protein Cren7]-N6-methyl-L-lysine
show the reaction diagram
F0NBH8
the enzyme Cren7 plays a major role in methylation of the crenarchaeal chromatin protein Cren7, Cren7 is a the crenarchaeal chromatin protein
-
-
?
S-adenosyl-L-methionine + [protein Cren7]-L-lysine
S-adenosyl-L-homocysteine + [protein Cren7]-N6-methyl-L-lysine
show the reaction diagram
F0NBH8
the enzyme Cren7 plays a major role in methylation of the crenarchaeal chromatin protein Cren7, Cren7 is a the crenarchaeal chromatin protein
-
-
?
S-adenosyl-L-methionine + [protein Dpo4]-L-lysine
S-adenosyl-L-homocysteine + [protein Dpo4]-N6-methyl-L-lysine
show the reaction diagram
F0NBH8
-
-
-
?
S-adenosyl-L-methionine + [protein FEN1]-L-lysine
S-adenosyl-L-homocysteine + [protein FEN1]-N6-methyl-L-lysine
show the reaction diagram
F0NBH8
-
-
-
?
S-adenosyl-L-methionine + [protein GINS15]-L-lysine
S-adenosyl-L-homocysteine + [protein GINS15]-N6-methyl-L-lysine
show the reaction diagram
F0NBH8
-
-
-
?
S-adenosyl-L-methionine + [protein PCNA1]-L-lysine
S-adenosyl-L-homocysteine + [protein PCNA1]-N6-methyl-L-lysine
show the reaction diagram
F0NBH8
-
-
-
?
S-adenosyl-L-methionine + [protein PCNA2]-L-lysine
S-adenosyl-L-homocysteine + [protein PCNA2]-N6-methyl-L-lysine
show the reaction diagram
F0NBH8
-
-
-
?
S-adenosyl-L-methionine + [protein PolB1]-L-lysine
S-adenosyl-L-homocysteine + [protein PolB1]-N6-methyl-L-lysine
show the reaction diagram
F0NBH8
-
-
-
?
S-adenosyl-L-methionine + [protein Sso7d2]-L-lysine
S-adenosyl-L-homocysteine + [protein Sso7d2]-N6-methyl-L-lysine
show the reaction diagram
F0NBH8
-
-
-
?
S-adenosyl-L-methionine + [ribosomal protein L11]-L-lysine
S-adenosyl-L-homocysteine + [ribosomal protein L11]-N6-methyl-L-lysine
show the reaction diagram
F0NBH8
-
-
-
?
S-adenosyl-L-methionine + [Topo-III]-L-lysine
S-adenosyl-L-homocysteine + [Topo-III]-N6-methyl-L-lysine
show the reaction diagram
F0NBH8
-
-
-
?
MC-1alpha + S-adenosyl-L-methionine
MC-1alpha N6-methylated at lysine37 + S-adenosyl-L-homocysteine
show the reaction diagram
-
high substrate specificity
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
a similar enzyme from Saccharomyces cerevisiae has low activity towards calf thymus histone but high activity towards ribosomal protein
-
-
-
additional information
?
-
-
not: lysine, ribonuclease A, cytochrome c, bovine serum albumin
-
-
-
additional information
?
-
-
low activity with myosin
-
-
-
additional information
?
-
-
H3-Lys9-methylation is an initiating and a maintenance modification for the X-chromosome silencing, in opposite to H3-Lys4-methylation, by a putative RNA/Xi-specific enzyme
-
-
-
additional information
?
-
-
histone methylation has significant effects on heterochromatin formation and transcriptional regulation
-
-
-
additional information
?
-
-
histone methylation has significant effects on heterochromatin formation and transcriptional regulation
-
-
-
additional information
?
-
Q9NQR1
histone methylation has significant effects on heterochromatin formation and transcriptional regulation
-
-
-
additional information
?
-
-
histone methylation has significant effects on heterochromatin formation and transcriptional regulation
-
-
-
additional information
?
-
-
methylation of H3 Lys9 correlates with transcription repression, H3 Lys4 correlates with activation
-
-
-
additional information
?
-
-
deregulation of SET-domain function has an important role in carcinogenesis, overview, effect in knock-out mice
-
-
-
additional information
?
-
-
growth factor independent 1 and G9a complex methylates the wild-type H3 substrate as well as the mutants replaced at K4, K36, and K79, substitution at K27 slightly reduces methylation of the H3 substrate, whereas substitution at K9 blocks methylation
-
-
-
additional information
?
-
Q9BYW2
HYPB and SUV39H1 possess HMTase activity that transferring 14C-labeled methyl group onto histone H3, HYPB displays higher activity of methylating nucleosomes than that of methylating purified histones, histone H3(K36R) fails to be methylated by GST-HYPB protein, HYPB selectively methylates histone H3-lysine 36
-
-
-
additional information
?
-
-
mDot1a directly or indirectly associates with and hypermethylated histone H3 K79 at specific portions of the ENaCalpha 5'-flanking region, inducing a local alteration of the chromatin structure that facilitates ENaCalpha mRNA expression
-
-
-
additional information
?
-
-
methyl-transfer reaction catalyzed by SET7/9 is a typical in-line SN2 nucleophilic substitution reaction with a transition state of 70% dissociative character, transfers only one methyl group to the unmodified histone-lysine residue H3-K4
-
-
-
additional information
?
-
-
minimal substrate methylated by G9a contains seven amino acids (TARKSTG) of the histone H3 tail
-
-
-
additional information
?
-
-
possesses HMTase activity that transferring 14C-labeled methyl group onto histone H3, histone H3(N4) fails to be methylated by GST-mG9a protein
-
-
-
additional information
?
-
O15047
Set1/CXXC finger protein 1 complex transfers tritiated methyl groups onto both purified core histones and recombinant histone H3, fails to catalyze methylation of histone H4, specificity for histone H3-Lys4 methylation
-
-
-
additional information
?
-
-
SET7/9 plays an essential catalytic role in significantly lowering the barrier for the methyl-transfer reaction step
-
-
-
additional information
?
-
-
modification of histone tails
-
-
-
additional information
?
-
-
SET1 mRNA is associated with a SET1C sub-complex
-
-
-
additional information
?
-
-
CXXC finger protein 1 is a component of the Setd1A and Setd1B histone H3K4 methyltransferase complex
-
-
-
additional information
?
-
-
methylation on H3(K4), H3(K36), and H3(K79) leads to activation of transcription, whereas methylation on H3(K9), H3(K27), and H4(K20) is associated with gene repression
-
-
-
additional information
?
-
-
SETD2 downregulates human ortholog of murine double min 2 protein expression by targeting its P2 promoter and then enhances p53 protein stability, enhances the transcriptional activity of p53, and regulates expression of select p53 target genes
-
-
-
additional information
?
-
-
SMYD3 requires both NHSC and EEL motifs for its HMT activity
-
-
-
additional information
?
-
-
the NF-kappaB factor RelB and histone H3 lysine methyltransferase G9a directly interact to generate epigenetic silencing in endotoxin tolerance
-
-
-
additional information
?
-
-
no activity is observed on trimethylated histone H3(K9) peptides either with or without ubiquitin
-
-
-
additional information
?
-
-
SDG724 prefers oligonucleosomes rather than core histones as a substrate
-
-
-
additional information
?
-
-
In addition to K20 (the target methylation site), R17 and H18 are very important specificity determinants for SET8 for substrate recognition. Any other amino acid introduced at these positions completely abolishes the activity of SET8. SET8 equally accepts K and R at position 19, followed by Y and other hydrophobic amino acids like L, H and I. Residues on the C-terminal side of K20 also play important roles in the specificity of SET8. The enzyme accepts majorly I at the -1 position followed by V. Other hydrophobic amino acids like F, Y and L give weaker methylation signals. SET8 also exhibits strong specificity on L22 and R23. At L22 some other hydrophobic amino acids are tolerated. At the +3 position, SET8 majorly prefers R, however it exhibits weak methylation when itis exchanged with other amino acids. SET8 activity is strongly reduced by the arginine methylation at positions R17 in case of H4 and R379 in case of p53
-
-
-
additional information
?
-
F0NBH8
the enzyme exhibits broad substrate specificity and is capable of methylating a number of recombinant Sulfolobus proteins overproduced in Escherichia coli. The enzyme methylates lysine residues in a rather sequence-independent manner
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + dimethylated histone H3(K9)
S-adenosyl-L-homocysteine + trimethylated histone H3(K9)
show the reaction diagram
-
the activity on dimethylated histone H3(K9) peptides is several folds lower than when monomethylated histone H3(K9) peptides are used
-
-
?
S-adenosyl-L-methionine + histone H3(K36)
?
show the reaction diagram
-
SDG724 mediates histone H3(K36)me2/3 deposition at MADS50 and RFT1
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
Q9NQR1
Lys20 of histone 4, SET8
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
Lys20 of histone 4, SET8
-
?
S-adenosyl-L-methionine + histone L-lysine
S-adenosyl-L-homocysteine + histone N6-methyl-L-lysine
show the reaction diagram
-
Lys9 of histone 3
-
?
S-adenosyl-L-methionine + monomethylated histone H3(K9)
S-adenosyl-L-homocysteine + trimethylated histone H3(K9)
show the reaction diagram
-
the SUVR4 product specificity shifts from di- to trimethylation in the presence of free ubiquitin. SUVR4 in vivo specifically converts monomethylated histone H3(K9) to trimethylated histone H3(K9) at transposons and pseudogenes
-
-
?
S-adenosyl-L-methionine + [protein Cren7]-L-lysine
S-adenosyl-L-homocysteine + [protein Cren7]-N6-methyl-L-lysine
show the reaction diagram
F0NBH8
the enzyme Cren7 plays a major role in methylation of the crenarchaeal chromatin protein Cren7
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
-
-
-
-
additional information
?
-
-
H3-Lys9-methylation is an initiating and a maintenance modification for the X-chromosome silencing, in opposite to H3-Lys4-methylation, by a putative RNA/Xi-specific enzyme
-
-
-
additional information
?
-
-
histone methylation has significant effects on heterochromatin formation and transcriptional regulation
-
-
-
additional information
?
-
-
histone methylation has significant effects on heterochromatin formation and transcriptional regulation
-
-
-
additional information
?
-
Q9NQR1
histone methylation has significant effects on heterochromatin formation and transcriptional regulation
-
-
-
additional information
?
-
-
histone methylation has significant effects on heterochromatin formation and transcriptional regulation
-
-
-
additional information
?
-
-
methylation of H3 Lys9 correlates with transcription repression, H3 Lys4 correlates with activation
-
-
-
additional information
?
-
-
deregulation of SET-domain function has an important role in carcinogenesis, overview, effect in knock-out mice
-
-
-
additional information
?
-
-
modification of histone tails
-
-
-
additional information
?
-
-
SET1 mRNA is associated with a SET1C sub-complex
-
-
-
additional information
?
-
-
no activity is observed on trimethylated histone H3(K9) peptides either with or without ubiquitin
-
-
-
additional information
?
-
-
SDG724 prefers oligonucleosomes rather than core histones as a substrate
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
S-adenosyl-L-methionine
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
-
the enzyme contains three tightly bound zinc ions that are important for maintaining the structural integrity and catalytic activity
additional information
F0NBH8
the enzyme requires no divalent cations for its activity
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-chloro-6,7-dimethoxyquinazoline
-
less than 30% inhibition at 0.001 mM
5-(6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-4-(1-methylpiperidin-4-ylamino)quinazolin-7-yloxy)pentanamide
-
less than 30% inhibition at 0.001 mM
-
6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)-4-(1-methylpiperidin-4-yloxy)quinazoline
-
less than 30% inhibition at 0.001 mM
-
6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
-
-
6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpyrrolidin-3-yl)quinazolin-4-amine
-
-
-
6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(piperidin-4-yl)quinazolin-4-amine
-
less than 30% inhibition at 0.001 mM
-
6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(tetrahydro-2H-pyran-4-yl)quinazolin-4-amine
-
less than 30% inhibition at 0.001 mM
-
6,7-dimethoxy-2-(4-methylpiperazin-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
-
-
6,7-dimethoxy-N-(1-methylpiperidin-4-yl)-2-(piperidin-1-yl)-quinazolin-4-amine
-
-
-
6,7-dimethoxy-N-(1-methylpiperidin-4-yl)-2-morpholinoquinazolin-4-amine
-
-
-
6,7-dimethoxy-N-methyl-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
less than 30% inhibition at 0.001 mM
-
6,7-dimethoxy-N-methyl-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine
-
less than 30% inhibition at 0.001 mM
-
6,7-dimethoxy-N2,N2-dimethyl-N4-(1-methylpiperidin-4-yl)-quinazoline-2,4-diamine
-
-
-
6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-7-(3-(methylamino)-propoxy)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
-
-
6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-7-(4-methylpentyloxy)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
-
-
6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)-7-(2-(2-(pyrrolidin-1-yl)ethoxy)ethoxy)quinazolin-4-amine
-
-
-
6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)-7-(3-(piperidin-1-yl)propoxy)quinazolin-4-amine
-
-
-
6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)-7-(3-(pyrrolidin-1-yl)propoxy)quinazolin-4-amine
-
-
-
6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)-7-(3-morpholinopropoxy)quinazolin-4-amine
-
-
-
6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)-7-(piperidin-3-ylmethoxy)quinazolin-4-amine
-
-
-
6-methoxy-7-(3-(methyl(propyl)amino)propoxy)-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
-
-
6-methoxy-7-(4-methoxybutoxy)-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
less than 30% inhibition at 0.001 mM
-
7-(2-(2-(dimethylamino)ethoxy)ethoxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
UNC0321, G9a inhibitor with picomolar potency and the most potent G9a inhibitor
-
7-(2-(dimethylamino)ethoxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
-
-
7-(3-(diethylamino)propoxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
-
-
7-(3-(dimethylamino)propoxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
UNC0224, potent G9a inhibitor
-
7-(4-(dimethylamino)butoxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
-
-
7-(5-(dimethylamino)pentyloxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
-
-
7-(5-aminopentyloxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
-
-
7-(6-(dimethylamino)ethoxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
-
-
aldosterone
-
-
aldosterone
-
at an early time point (2 h) downregulates the steady-state level of mDot1a mRNA and this precedes, and is associated with, downregulation of histone H3 K79 methylation in mIMCD3 cells
BIX-01294
-
inhibits histone lysine methyltransferase G9a and shows no activity against histone lysine methyltransferase Suv39H1
BIX-01294
-
-
BIX-01294
-
specific inhibitor of enzyme forms G9A and GLP
BIX-01338
-
unselective inhibitor
BIX-01338
-
-
chaetocin
-
-
Cu2+
-
-
CXXC finger protein 1
-
restricts the activity of the Set1 histone methyltransferase complex
-
cyclohexamide
-
decreases nuclear G9a protein but does not prevent its relative increase during hypoxic stress
DNA
-
-
E72
-
inhibits enzyme form GLP
-
eosin
-
AMI-5, numerous different substitutes of eosin synthesized and tested for inhibition
N-(1-benzylpiperidin-4-yl)-6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine
-
BIX01294, selective small molecule inhibitor of enzyme forms G9a and GLP
-
N-cyclohexyl-6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)-quinazolin-4-amine
-
less than 30% inhibition at 0.001 mM
-
N-cyclopropyl-6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)-quinazolin-4-amine
-
less than 30% inhibition at 0.001 mM
-
N-isopropyl-6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)-quinazolin-4-amine
-
less than 30% inhibition at 0.001 mM
-
N1-(2-(6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-4-(1-methylpiperidin-4-ylamino)quinazolin-7-yloxy)ethyl)-N1,N2,N2-trimethylethane-1,2-diamine
-
-
-
N2,N2-diethyl-6,7-dimethoxy-N4-(1-methylpiperidin-4-yl)quinazoline-2,4-diamine
-
-
-
RNA
-
-
S-adenosyl-L-cysteine
-
-
S-adenosyl-L-ethionine
-
-
S-adenosyl-L-homocysteine
-
-
S-adenosyl-L-homocysteine
-
-
S-adenosyl-L-homocysteine
-
-
S-adenosyl-L-homocysteine
-
-
S-adenosyl-L-homocysteine
-
competitive inhibition
sinefungin
-
-
TCEP
-
suppresses activity in a dose-dependent manner
-
tert-butyl 4-(6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-4-(1-methylpiperidin-4-ylamino)quinazolin-7-yloxy)butylcarbamate
-
less than 30% inhibition at 0.001 mM
-
trimethylated histone H3(K4)
-
-
-
UNC0224
-
picomolar inhibition of enzyme form G9A
-
Zn2+
-
-
Hg2+
-
-
additional information
-
hypoxia does not cause any measurable changes of G9a mRNA at earlier time intervals (1 and 3 hours) but leads to a significant decrease at 6 hours after challenge
-
additional information
-
not affected by dithiothreitol
-
additional information
-
SUVR4 enzyme activity is not affected by monomethylated histone H3(K4)
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
deferoxamine
-
increases G9a protein and activity in A549 cells, moreover, increases the methyltransferase activity of overexpressed GFP-hG9a fusion proteins
dimethyloxalylglycine
-
increases G9a protein and activity in A549 cells
Sulfhydryl reducing agent
-
required for optimal activity
-
heat shock protein 90alpha
-
the interaction of SMYD2 with heat shock protein 90alpha enhances SMYD2 histone methyltransferase activity and specificity for histone H3 at lysine 4 by 10fold, histone H3K36 methyltransferase activity is independent of ist interaction with heat shock protein 90alpha
-
additional information
-
hypoxia increases nuclear G9a protein by posttranslational mechanisms and its methyltransferase activity
-
additional information
-
the p33ING2-associated histone methyltransferase shows an increased methylation activity if lysine 9 is methylated
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0074
biotinyl-MARTKQTARKSTGGKAPRKQ
-
-
0.00031
histone H1
-
isozyme VA
-
0.00044
histone H1
-
isozyme VB
-
0.00026
Histone H3
-
recombinant substrate
-
0.0009
Histone H3
-
wild-type substrate
-
0.0011
histone H3 (1-13)
-
wild-type substrate
-
0.0006
histone H3 (T11phos)
-
wild-type substrate
-
0.2762
histone H3(K27)
-
wild-type
-
0.4274
histone H3(K27)
-
mutant Y50F
-
3.9
histone H3(K27)
-
mutant F52Y
-
0.00017
histone H3(K27A)
-
recombinant substrate
-
0.00023
histone H3(K4A)
-
recombinant substrate
-
0.0022
histone K4-acetylK9
-
-
-
0.0006
histone K4-trimethylK9
-
-
-
0.00012
S-adenosyl-L-methionine
-
mutant enzyme G18A/G20A, using p53 as cosubstrate, in 50 mM Tris pH 9.0, at 22C
0.00031
S-adenosyl-L-methionine
-
wild type enzyme, using p53 as cosubstrate, in 50 mM Tris pH 9.0, at 22C
0.0006
S-adenosyl-L-methionine
-
mutant enzyme G18A/G20A, using p53 as cosubstrate, in 50 mM Tris pH 9.0, at 22C
0.00068
S-adenosyl-L-methionine
-
wild type enzyme, using p53 as cosubstrate, in 50 mM Tris pH 9.0, at 22C
0.0012 - 0.0013
S-adenosyl-L-methionine
-
in methylation buffer containing 50 mM glycine (pH 9.8), 2 mM dithiothreitol, 0.025 mg/ml bovine serum albumin, 10% (v/v) glycerol, at 22C
0.0017
S-adenosyl-L-methionine
-
-
0.003
S-adenosyl-L-methionine
-
-
0.027
S-adenosyl-L-methionine
-
isozyme VA
0.0345
S-adenosyl-L-methionine
-
isozyme VB
0.0015
histone K4AK9
-
-
-
additional information
additional information
-
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.038
biotinyl-MARTKQTARKSTGGKAPRKQ
-
-
0.02167
Histone H3
-
recombinant substrate
-
0.024
Histone H3
-
wild-type substrate
-
0.02056
histone H3 (1-13)
-
wild-type substrate
-
0.001806
histone H3 (S10phos)
-
wild-type substrate
-
0.005
histone H3 (T11phos)
-
wild-type substrate
-
1.32
histone H3(K27)
-
wild-type
-
1.36
histone H3(K27)
-
mutant Y50F
-
0.0161
histone H3(K27A), histone H3(K4A)
-
recombinant substrate
-
0.0089
histone K4-acetylK9, histone K4-trimethylK9
-
-
-
0.01194
histone K4AK9
-
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00000063
7-(2-(2-(dimethylamino)ethoxy)ethoxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.04
S-adenosyl-L-ethionine
-
isozyme VA
0.044
S-adenosyl-L-ethionine
-
isozyme VB
0.00035
S-adenosyl-L-homocysteine
-
wild type enzyme, using p53 as cosubstrate, in 50 mM Tris pH 9.0, at 22C
0.00148
S-adenosyl-L-homocysteine
-
isozyme VA
0.0016
S-adenosyl-L-homocysteine
-
isozyme VB
0.071
S-adenosyl-L-homocysteine
-
-
0.0015
sinefungin
-
isozyme VB
0.0019
sinefungin
-
isozyme VA
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00033
6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.00091
6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpyrrolidin-3-yl)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.00015
6,7-dimethoxy-2-(4-methylpiperazin-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.00055
6,7-dimethoxy-N-(1-methylpiperidin-4-yl)-2-(piperidin-1-yl)-quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.0016
6,7-dimethoxy-N-(1-methylpiperidin-4-yl)-2-morpholinoquinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.0011
6,7-dimethoxy-N2,N2-dimethyl-N4-(1-methylpiperidin-4-yl)-quinazoline-2,4-diamine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.00012
6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-7-(3-(methylamino)-propoxy)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.0034
6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-7-(4-methylpentyloxy)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.000057
6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)-7-(2-(2-(pyrrolidin-1-yl)ethoxy)ethoxy)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.000025
6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)-7-(3-(piperidin-1-yl)propoxy)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.000008
6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)-7-(3-(pyrrolidin-1-yl)propoxy)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.00088
6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)-7-(3-morpholinopropoxy)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.0015
6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)-7-(piperidin-3-ylmethoxy)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.00051
6-methoxy-7-(3-(methyl(propyl)amino)propoxy)-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.000009
7-(2-(2-(dimethylamino)ethoxy)ethoxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.00011
7-(2-(dimethylamino)ethoxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.000052
7-(3-(diethylamino)propoxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.000043
7-(3-(dimethylamino)propoxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.00014
7-(4-(dimethylamino)butoxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.000095
7-(5-(dimethylamino)pentyloxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.000235
7-(5-aminopentyloxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.0015
7-(6-(dimethylamino)ethoxy)-6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.0007
BIX-01294
-
G9a-like protein lysine methyltransferase, in 20 mM Tris (pH 8.5), at 30C
0.0019
BIX-01294
-
histone lysine methyltransferase G9a, in 20 mM Tris (pH 8.5), at 30C
0.0027
BIX-01294
-
histone lysine methyltransferase G9a
0.005
BIX-01338
-
histone lysine methyltransferase G9a
0.00018
N-(1-benzylpiperidin-4-yl)-6,7-dimethoxy-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.000345
N1-(2-(6-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-4-(1-methylpiperidin-4-ylamino)quinazolin-7-yloxy)ethyl)-N1,N2,N2-trimethylethane-1,2-diamine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
0.00091
N2,N2-diethyl-6,7-dimethoxy-N4-(1-methylpiperidin-4-yl)quinazoline-2,4-diamine
-
enzyme form G9a, in PBS buffer, pH 7.4, at 22C
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.000285
-
isozyme VA
0.00202
-
isozyme VB
0.0027
-
-
additional information
-
-
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8
F0NBH8
assay at
8.5 - 9
-
-
9
-
assay at
9.1
-
SMYD2 activity increases dramatically from pH 8.5 to pH 9.2, peaking at pH 9.1
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5 - 9.5
-
at pH 5.5 and pH 9.5 about 50% of activity maximum
7.5 - 9.9
-
about 50% of activity maximum at pH 7.5 and 9.9
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
-
assay at
32
-
SMYD2 has maximal activity at about 32C, with activity rapidly dropping at temperatures above 37C
37
-
assay at
50
F0NBH8
assay at
60 - 70
F0NBH8
-
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 40
-
-
25 - 90
F0NBH8
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
Q8R5A0, Q9CWR2
-
Manually annotated by BRENDA team
Q8R5A0, Q9CWR2
highest levels of Smyd2 mRNA transcripts
Manually annotated by BRENDA team
-
PRDM8 of 70 kDa
Manually annotated by BRENDA team
Q8R5A0, Q9CWR2
at day 13.5, especially heart and hypothalamus of the brain
Manually annotated by BRENDA team
-
embryonic fibroblast cell
Manually annotated by BRENDA team
-
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
-
embryonic fibroblast cell
Manually annotated by BRENDA team
Q8R5A0, Q9CWR2
highest levels of Smyd2 mRNA transcripts
Manually annotated by BRENDA team
-
PRDM8 of 30 kDa is expressed most prominently in cardiomyocytes from the heart
Manually annotated by BRENDA team
-
interaction between growth factor independent 1 and G9a in vivo
Manually annotated by BRENDA team
Q8R5A0, Q9CWR2
highest levels of Smyd2 mRNA transcripts
Manually annotated by BRENDA team
-
PRDM8 of 30 kDa
Manually annotated by BRENDA team
Q8R5A0, Q9CWR2
highest levels of Smyd2 mRNA transcripts
Manually annotated by BRENDA team
-
PRDM8 of 70 kDa and of 30 kDa
Manually annotated by BRENDA team
Q8R5A0, Q9CWR2
highest levels of Smyd2 mRNA transcripts
Manually annotated by BRENDA team
-
PRDM8 of 70 kDa
Manually annotated by BRENDA team
Q8R5A0, Q9CWR2
highest levels of Smyd2 mRNA transcripts
Manually annotated by BRENDA team
Q8R5A0, Q9CWR2
highest levels of Smyd3 expression
Manually annotated by BRENDA team
-
PRDM8 is expressed most prominently in striated skeletal muscle from the tongue
Manually annotated by BRENDA team
additional information
-
found in all rat organs tested
Manually annotated by BRENDA team
additional information
-
MES cell and HIF-1alpha cell
Manually annotated by BRENDA team
additional information
-
mIMCD3 cell, mDot1a expressed and maintained at low levels
Manually annotated by BRENDA team
additional information
-
PRDM8 is not expressed in intestinal smooth muscles
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
subcellular distribution is not definitely determined
Manually annotated by BRENDA team
-
Dpy-30 functions in the endosome to trans-Golgi network transport of cation-independent mannose 6-phosphate receptor
Manually annotated by BRENDA team
-
subcellular distribution is not definitely determined
-
Manually annotated by BRENDA team
-
subcellular distribution is not definitely determined
Manually annotated by BRENDA team
O15047
GFP-Set1 fusion protein in nuclear speckles that are largely excluded from DAPI-bright regions, thus euchromatin localization, FLAG-CXXC finger protein 1 and GFP-Set1 colocalize to sub-nuclear regions that are distinct from regions of DAPIbright heterochromatin
Manually annotated by BRENDA team
-
overexpressed exogenous G9a protein
Manually annotated by BRENDA team
-
SUV420H2 is strongly associated to pericentric heterochromatin, the N-terminus of SUV420H2 comprising then catalytically active SET domain is dispersed within the nucleus, whereas the C-terminal part of the protein is associated with heterochromatin
Manually annotated by BRENDA team
-
the full-length of PRDM8 is localized exclusively in the nuclear region
Manually annotated by BRENDA team
-
the enzyme localizes at euchromatin and heterochromatin
Manually annotated by BRENDA team
-
subcellular distribution is not definitely determined
Manually annotated by BRENDA team
additional information
-
G9a protein not detected in the cytoplasm
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Schizosaccharomyces pombe (strain 972 / ATCC 24843)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
18000
F0NBH8
gel filtration
725281
27000
-
gel filtration
661758
30000
-
the 30 kDa PRDM8 is most abundant in testis, heart, liver, and kidney, SDS-PAGE
702068
34000
-
isozyme VB, gel filtration
485347
45000
-
SDS-PAGE
485352
45000
Q9NQR1
SDS-PAGE
485352
49700
-
calculated from amino acid sequence
705714
52000
-
about 52000 Da, SDS-PAGE
702886
55000
-
isozyme VA, gel filtration
485347
70000
-
the 70 kDa full-length PRDM8 is most abundant in brain and testis, SDS-PAGE
702068
82000
-
gel filtration
485348
170000
-
Western blot analysis, mDot1a in the kidney
671225
400000 - 800000
-
the activity peak migrates at high molecular mass (400000-800000 Da), gel filtration
704635
450000
O15047
Western analysis of Set1/CXXC finger protein 1 complex
674513
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 171000 to 232000, calculated
?
-
x * 180000, enzyme form dG9a, SDS-PAGE
?
-
x * 53000, MALDI-TOF mass spectrometry, x * 53100, calculated from amino acid sequence
?
-
x * 60000, GST-tagged SET8 domain, SDS-PAGE
?
-
x * 632800, all dSet1-complex subunits, calculated from amino acid sequence, x * 670000, all dSet1-complex subunits, SDS-PAGE
dimer
-
2 * 15100, calculated
monomer
F0NBH8
-
monomer
Q9NQR1
1 * 45000, SDS-PAGE
monomer
-
1 * 45000, SDS-PAGE
additional information
-
enzyme interacts in vivo and in vitro with CCAAT displacement protein/cut homolog. Transcriptional repressor function of cut homolog is mediated through enzyme activity
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
in complex with BIX-01294, hanging drop vapor diffusion method, using 0.1 M HEPES pH 7.5, 18-20% (w/v) polyethylene glycol 4000 and 7-10% (v/v) isopropanol, in the absence or presence of DMSO (6-36% v/v)
-
the ternary structures of SET7-estrogen receptor peptide-AdoMet analog are solved by molecular replacement
Q8WTS6
complexed with S-adenosyl-L-homocysteine, hanging drop method, 25C, reservoir solution contains HEPES 100 mM, pH 6.8, sodium acetate 1.2-1.35 M, structure analysis
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5
-
enzyme becomes irreversibly inactivated at pH lower than 5.0
485348
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45
-
5 min, 50% loss of activity without addition of histone, no loss of activity with addition of histone, 20 min, 72% loss of activity without addition of histone, 65% loss of activity with addition of histone
485350
60
-
3 min, 97% loss of activity
485350
80
F0NBH8
half-life: 30 min
725281
90
F0NBH8
half-life: 10 min
725281
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
SMYD2 shows minimal activity in HEPES buffer with pH values below 7.5 and moderate activity in Tris buffer from pH 7.5 to pH 8.5
-
histones protect against heat inactivation at 45C, no effect at 60C
-
proteins Swd1 and Swd3 do not impact the transcriptional levels of SET1 but are important to mediate proper Set1 protein levels or stability likely by directly interacting with Set1. Acidic and basic patch interaction between Set1 and Swd1 is essential for proper Set1 protein levels
-
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Tween-20
-
0.001% (w/v) Tween-20 enhances SMYD2 methyltransferase activity by more than 4fold. The enzyme remains stable in the presence of 0.01-0.05% (v/v) Tween-20
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
glutathione-Sepharose bead chromatography
-
partial
-
recombinant C-terminal SET domain and the unique N-terminal fragment of Set1p
-
glutathione-Sepharose column chromatography
Q7SXS7
2 isozymes
-
; Ni-NTA bead chromatography, glutathione bead chromatography, and Superdex 200 gel filtration
O96028, Q9BYW2
ammonium sulfateprecipitation, heparin-Sepharose column chromatography, DEAE 5PW column chromatography, Mono S column chromatography, and Superose 6 gel filtration
-
anti-FLAG antibody immunoprecipitation
-
Ni-NTA agarose column chromatography and Superdex 200 gel filtration
-
nickel-chelating column chromatography, HiTrap-Q column chromatography, and Superdex-75 and -200 gel filtration
-
partial
Q9NQR1
Sepharose bead chromatography
-
tandem affinity purification
-
by immunoprecipitation; by immunoprecipitation
Q8R5A0, Q9CWR2
purity greater than 95%
-
His bind resin column chromatography
-
recombinant from E. coli
-
glutathione Sepharose-4B column chromatography
-
partial, similar enzyme with low activity towards calf thymus histone but high activity towards ribosomal protein
-
tandem affinity purification
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
Q7SXS7
glutathione-S-transferase-fusion protein, SET gene
-
expressed in S2 cells
-
-
Q8WTS6
; GST-SET domain fusion proteins are expressed in Escherichia coli, SET2-C is expressed in baculovirus insect cells
O96028, Q9BYW2
cotransfection of growth factor independent 1 with both HA epitope-tagged G9a and Myc epitope-tagged Suv39H1 into HeLa cells
-
expressed in Escherichia coli BL21 cells
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in HEK-293 cells
-
expressed in LNCaP, MCF-7, and A-549 cells
-
expressed in Sf21 insect cells
-
expressed in U2OS cells
-
expression of wild-type SET9 and mutants in Escherichia coli, His-tagged
-
FLAG-tagged and untagged SMYD3 proteins are expressed in HEK-293T and MCF-7 cells
-
for HMTase activity assays and glutathione S-transferase pull-down assays subcloned into pGEX-5X1 vector, for transactivation assays subcloned into pBIND vector, for coimmunoprecipitation assays subcloned into pFLAG-CMV4 vector, expressed in Escherichia coli strain BL21
Q9BYW2
glutathione-S-transferase-fusion protein, SET gene
Q9NQR1
into the pEGFP-C2 vector
O15047
recombinant full-length G9a is obtained using a baculoviral expression system
-
TAP-tagged protein is expressed in L929 cells
-
expressed as a GST fusion in Escherichia coli, 293T cells transfected with plasmid expressing Myc-tagged wild-type or mutant Smyd2, NIH3T3 cells transfected with Smyd2-Myc, overexpression of Smyd2 in NIH3T3 cells significantly reduces cell growth; expressed as a GST fusion in Escherichia coli, 293T cells transfected with plasmids expressing Myc-tagged wild-type or mutant Smyd3, NIH3T3 cells transfected with Smyd3-Myc, overexpression of Smyd3 augments cell growth when introduced into NIH3T3 cells
Q8R5A0, Q9CWR2
expressed HEK-293 cells
-
into vector pcDNA3.1 (+)
-
PCR-amplified EcoRI-XhoI insert encoding the murine long form of G9a cloned into the EcoRI-XhoI sites of pSG5.HA and pSG5.FLAG, PCR-amplified EcoRI-SalI inserts of G9a residues 1-333, 72-333, 330-690, 685-1018, 936-1263 (deltaANK), 1-1088 (deltaSET), 730-1263, and 464-1263 cloned into the EcoRI-SalI sites of the vector pM for Gal4 DNA binding domain fusions and into the EcoRI-XhoI sites of pSG5.HA or pSG5.FLAG, expression in CV-1 and Cos-7 cells
-
the 70 kDa full-length form is expressed in HEK-293T cells
-
expressed in Escherichia coli strain XL1 blue
-
expressed in Escherichia coli BL21(RIL) cells
-
overexpression in Escherichia coli BL21, His-tagged protein
-
expressed in Escherichia coli
-
expressed in Escherichia coli
-
overexpression in Escherichia coli
F0NBH8
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the expression of SET7/9 is not altered by tissue necrosis factor-alpha treatment
-
RE-IIBP expression and histone methylation are increased in leukemia patients
-
the enzyme is overexpressed in human cancer cells
-
constant elevation of TX1 expression is observed during seed development with highest transcript intensities for the germinating seed coleoptyle and immature inflorescence and lowest transcript intensities were monitored on leaves and on pre-anthesis tissues. TX1 gene expression is inceased in response to drought stress
F4YY96
the expression of 70 kDa PRDM8 in brain and testis abruptly increases 3 weeks after birth
-
DNA methylation of the G9a and Suv39h1 genes is up-regulated by choline deficiency, suggesting that the expression of these enzymes is under negative control by methylation of their genes
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H299A
-
overlap PCR, destroyed SET gene, no activity remaining
F679Y
-
the mutant is tolerated with about 2fold reduction compared with wild type, the mutant retains the capacity to produce trimethylated histone H3(K27)
C483A
-
no activity, the SET domain cysteine 483 is a critical residue for the histone methyltransferase activity of RE-IIBP
DELTAGEE
-
the deletion mutant shows no histone methyltransferase activity
DELTANHSC
-
the deletion mutant shows no histone methyltransferase activity
G18A/G20A
-
the mutations impaire S-adenosyl-L-methionine binding and significantly decrease enzymatic activity
H2113K
-
methyltransferase-deficient mutant
R477A
-
no activity, the SET domain 477 is a critical residue for the histone methyltransferase activity of RE-IIBP
Y245A
-
the mutant acts as a trimethylase
Y245F
-
the mutation converts the enzyme from a mono- to a dimethyltransferase
deltaANK
-
is inactive as a coactivator
deltaSET
-
lacks the enzymatic activity in vitro, synergistic coactivator function observed with glucocorticoid receptor interacting protein 1, coactivator-associated arginine methyltransferase 1 is reduced but not eliminated
Y239F
Q8R5A0, Q9CWR2
mutant Smyd3, no HKMT activity
Y240F
Q8R5A0, Q9CWR2
mutant Smyd2, no HKMT activity
D209A
-
in solution experiments with the wild type histone H3 sequence, the mutant shows a 100fold reduced activity as compared to wild-type Dim-5
D209S
-
in solution experiments with the wild type histone H3 sequence, the mutant shows a 100fold reduced activity as compared to wild-type Dim-5
E227A
-
in solution experiments with the wild type histone H3 sequence, the mutant shows a 10fold reduced activity as compared to wild-type Dim-5
E227S
-
in solution experiments with the wild type histone H3 sequence, the mutant shows a 10fold reduced activity as compared to wild-type Dim-5
F281W
-
shows catalytic activity
F281Y
-
shows catalytic activity
Y178F
-
shows catalytic activity, although the methylation rates of this variant are low
Y178V
-
shows catalytic activity
F52Y
-
can only mono- and di- but not tri-methylate H38(K27)
Y798Q
-
the point mutation within the Tudor domain prevents Rad9 binding to chromatin and Rad9 hyperphosphorylation after DNA damage
D34K
F0NBH8
completely inactive mutant enzyme
E14A
F0NBH8
mutant enzyme shows about 60% of the wild-type activity
G36R
F0NBH8
completely inactive mutant enzyme
H6A
F0NBH8
mutant enzyme shows about 65% of the wild-type activity
K15A
F0NBH8
mutant enzyme shows about 120% of the wild-type activity
P11A
F0NBH8
mutant enzyme shows about 20% of the wild-type activity
P13A
F0NBH8
mutant enzyme shows about 65% of the wild-type activity
P5A
F0NBH8
mutant enzyme shows about 80% of the wild-type activity
P8A
F0NBH8
mutant enzyme shows about 65% of the wild-type activity
R19A
F0NBH8
mutant enzyme shows about 125% of the wild-type activity
T12A
F0NBH8
mutant enzyme shows about 5% of the wild-type activity
V10A
F0NBH8
mutant enzyme shows about 45% of the wild-type activity
V16A
F0NBH8
mutant enzyme shows about 80% of the wild-type activity
V17A
F0NBH8
mutant enzyme shows about 50% of the wild-type activity
V7A
F0NBH8
mutant enzyme shows about 40% of the wild-type activity
Y9A
F0NBH8
mutant enzyme shows about 90% of the wild-type activity
E14A
-
mutant enzyme shows about 60% of the wild-type activity
-
G36R
-
completely inactive mutant enzyme
-
K15A
-
mutant enzyme shows about 120% of the wild-type activity
-
R19A
-
mutant enzyme shows about 125% of the wild-type activity
-
V16A
-
mutant enzyme shows about 80% of the wild-type activity
-
additional information
-
the two SDG8 T-DNA insertion mutant alleles sdg8-2 and sdg8-4 have no detectable SDG8 transcripts
additional information
-
set1 null mutant, heterozygous mutant, and reinsertion strains, HMT activity of the set1 null mutant strain is significantly reduced compared with strain CAI12, heterozygous mutant and reinsertion strains, disruption of SET1 results in complete loss of methylation of histone 3 at lysine residue 4, hyperfilamentous growth under embedded conditions, less negative cell surface charges and diminished adherence to epithelial cells, effects reversed upon gene reinsertion at a disrupted locus
additional information
Candida albicans CAI12
-
set1 null mutant, heterozygous mutant, and reinsertion strains, HMT activity of the set1 null mutant strain is significantly reduced compared with strain CAI12, heterozygous mutant and reinsertion strains, disruption of SET1 results in complete loss of methylation of histone 3 at lysine residue 4, hyperfilamentous growth under embedded conditions, less negative cell surface charges and diminished adherence to epithelial cells, effects reversed upon gene reinsertion at a disrupted locus
-
F681Y
-
the mutation dramatically reduces PRC2 HMTase
additional information
-
mutations in enzyme gene result in Polycomb-group phenotypes, phenotypes characteristic of trithorax-group mutants, disrupt telomeric silencing, but do not affect centric heterochromatin
additional information
-
each SET domain mutation disrupts PRC2 histone methyltransferase, based on known SET domain structures, the mutations likely affect either the lysine-substrate binding pocket, the binding site for the adenosylmethionine methyl donor, or a critical tyrosine predicted to interact with the substrate lysine epsilon-amino group. The CXC mutant retains catalytic activity, Lys-27 specificity, and trimethylation capacity.
additional information
-
the E(z)Trm mutation increases the histone H3 (K27) trimethylation efficiency of catalytic subunit E(Z) of Polycomb Repressive Complex 2
H297A
-
catalytically inactive mutant
additional information
Q9BYW2
arginine 1122-to-histidine mutant of HYPB, both the HMTase activity and auto-methylation activity is significantly impaired
H1166K
-
lacks the enzymatic activity in vitro, synergistic coactivator function observed with glucocorticoid receptor interacting protein 1, coactivator-associated arginine methyltransferase 1 is reduced but not eliminated
additional information
-
construction of several SET domain family deficient or knock-out mutants, analysis of effect on carcinogenesis
additional information
-
G9a deficient embryos, drastically decreased activity in vivo
additional information
-
in G9a-/- embryonic stem cells, the increase in dimethylated histone H3 lysine 9 is significantly mitigated following hypoxia challenge
additional information
-
methyltransferase-dead mutant pEGFP-mDot1aRCR, mENaCalpha mRNA levels in cells transfected with the methyltransferase-dead mutant are almost twice that of vector-transfected cells, knockdown of mDot1a mRNA levels by RNA interference augments endogenous mENaCalpha expression and activity of mENaCalpha-promoter luciferase reporter
Y50F
-
nearly abolishes di- and tri-methylation of H3(K27), but does not affect the mono-methylation
additional information
-
HMT activity of set1 null mutant strain is significantly reduced compared with the wild-type strain
additional information
-
the removal of the WD40 domain-containing subunits Swd1 and Swd3 of the complex of proteins associated with Set1, which contribute to the stability of Set1, leads to a loss of Set1 protein and consequently a complete loss of histone H3(K4) methylation
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
SET1 regulates multiple processes important to the pathogenesis of candidiasis, antibody responses against a unique N-terminal fragment of Candida albicans Set1p distinguish patients with candidiasis from controls without disease, the Set1p N-terminal fragment does not exhibit significant homology to eukaryotic or microbial proteins, and might represent a novel therapeutic, preventive or diagnostic target
medicine
Candida albicans CAI12
-
SET1 regulates multiple processes important to the pathogenesis of candidiasis, antibody responses against a unique N-terminal fragment of Candida albicans Set1p distinguish patients with candidiasis from controls without disease, the Set1p N-terminal fragment does not exhibit significant homology to eukaryotic or microbial proteins, and might represent a novel therapeutic, preventive or diagnostic target
-
analysis
-
ab initio quantum mechanical/molecular mechanical molecular dynamics simulations with the umbrella sampling method to determine free energy profiles for histone lysine methylation catalyzed by SET7/9 and its corresponding uncatalyzed reaction in aqueous solution, activation free energy barrier for the methyl transfer reaction catalyzed by SET7/9 is 22.5 kcal/mol, which agrees with the experimental value of 20.9 kcal/mol very well, SET7/9 lowers the barrier for the methyl-transfer reaction step by 8.4 kcal/mol compared with the uncatalyzed reaction
analysis
-
multiple ab initio quantum mechanical/molecular mechanical free energy calculations and molecular dynamics simulations for the investigation of the methyl-transfer reaction catalyzed by SET7/9
medicine
-
G9a plays an important role in the hypoxia-induced dimethylated histone H3 lysine 9, which inhibits the expression of several genes that likely leads to solid tumor progression
medicine
Q9BYW2
HYPB may coordinate histone methylation and transcriptional regulation in mammals and open perspective for the further study of the potential roles of HYPB protein in hematopoiesis and pathogenesis of Huntington disease, HYPB and SET2 may be functional homologue and the regions of high similarities may define functionally important domains within these proteins
analysis
-
sequence context of modified residue affects G9a activity and modification in the proximal amino acids influences methylation
medicine
-
G9a plays an important role in the hypoxia-induced dimethylated histone H3 lysine 9, which inhibits the expression of several genes that likely leads to solid tumor progression
analysis
-
development of a microplate biotin/avidin peptide methylation assay, which is convenient, very accurate, reproducible, and inexpensive. Because it yields quantitative results, it can be employed for a characterization of the enzymatic properties of histone lysine methyltransferases and other protein methyltransferases and is also well suited for high-throughput applications
analysis
-
three-dimensional solution structure of vSET bound to S-adenosyl-L-homocysteine and a histone H3 peptide containing mono-methylated lysine 27, only invariant active site residue tyrosine 105 in vSET facilitates methyl transfer from S-adenosyl-L-homocysteine to the substrate lysine by aligning intermolecular interactions in the lysine access channel of the enzyme
medicine
-
SUV39H1/2 (KMT1A/B) shows overexpression in dietary induced tumors and increased mRNA levels in colon cancer patients, G9a (KMT1C) contributes to histone 3(K9) dimethylation that is involved in suppressor gene silencing and knockdown inhibits cancer cell growth, Eu-HMTase1 (KMT1D) is overexpressed in gland tumors, SETDB1/ESET (KMT1E) cooperates with DNA methyltransferase in promotor silencing in tumors, MLL1 (KMT2A) mutations/rearrangements are involved in leukemogenesis, MLL4 (KMT2D) is involved in hepatitis B virus dependent liver carcinogenesis, SMYD2 (KMT3C) show suppression of p53 transcriptional activity, SMYD3 enhances breast cancer cell growth due to overexpression an shows overexpression in colorectal and hepatocellular carcinoma, DOT1L (KMT4) is involved in leukemogenesis, SET8/PR-SET7 (KMT5A) suppresses p53 dependent transcription, EZH2 (KMT6) is associated with aggressive tumor growth in several tumor types and is marker for precancerous state in breast cancerogenesis and for aggressive breast cancer, promotes proliferation and invasiveness of prostate cancer cells, and is useful as a biomarker for poor prostate cancer prognosis
additional information
-
growth factor independent 1 interacts with G9a and recruits G9a and histone deacetylase 1 to its target promoters, including the cell cycle regulator p21Cip/WAF1 and other cell cycle regulators, in order to repress transcription through histone H3(K9) dimethylation
medicine
Q8R5A0, Q9CWR2
Smyd2 is expressed in a wide range of normal, tumor, and diseased tissues, Sin3A-mediated deacetylation within the coding regions of active genes is directly linked to the histone methyltransferase activity of Smyd2. Moreover, Smyd2 appears to restrain cell proliferation, likely through direct modulation of chromatin structure
additional information
-
functions as a coactivator for nuclear receptors, cooperating synergistically with nuclear receptor coactivators glucocorticoid receptor interacting protein 1, coactivator-associated arginine methyltransferase 1, and p300 in transient transfection assays, synergy depends strongly on the arginine-specific protein methyltransferase activity of CARM1 but does not absolutely require the enzymatic activity of G9a and is specific to CARM1 and G9a among various protein methyltransferases, link between histone arginine and lysine methylation and a mechanism for controlling whether G9a functions as a corepressor or coactivator
additional information
-
mDot1a is a novel aldosterone regulated histone modification enzyme, and, through binding the ENaCalpha promoter and hypermethylating histone H3 K79 associated with the ENaCalpha promoter, a negative regulator of ENaCalpha transcription