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Information on EC 2.1.1.360 - [histone H3]-lysine79 N-trimethyltransferase and Organism(s) Homo sapiens and UniProt Accession Q8TEK3
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2.1.1.360 [histone H3]-lysine79 N-trimethyltransferaseIUBMB Comments
The enzyme successively methylates the L-lysine79 residue of histone H3 (H3K79), ultimately generating a trimethylated form. These modifications influence the binding of chromatin-associated proteins. This is the only known methylation event of a lysine residue within the core region of a histone, as all other such modifications occur at the tail.
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- 2.1.1.360
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psoriatic
- arthritis
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autocalibrating
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acceleration
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k-space
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artifact
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coil
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noise
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phantom
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enthesitis
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signal-to-noise
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rheumatology
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undersampled
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echo
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aliasing
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dactylitis
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rheumatologist
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interpolation
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dermatologists
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tesla
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self-calibrated
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breath-holding
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g-factors
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cartesian
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omeract
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stockholm
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trainees
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free-breathing
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interleaved
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nyquist
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single-shot
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prologue
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phase-encoding
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spirit
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eular
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in-plane
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contrast-to-noise
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breakout
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plenary
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echo-planar
- spondyloarthritis
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multi-slice
- medicine
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precession
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32-channel
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
hide(Overall reactions are displayed. Show all >>)
Synonyms
grappa, h3k79 methyltransferase, histone h3k79 methyltransferase, mdot1a, dot1-like protein, h3k79 methylase, histone h3 lysine-79 methyltransferase, histone 3 lysine 79 methyltransferase (h3k79me1/me2/me3), 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
DOT1L
DOT1L
-
-
-
-
KMT4
-
-
-
-
PATHWAY SOURCE
PATHWAYS
KEGG
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:[histone H3]-L-lysine79 N6-trimethyltransferase
The enzyme successively methylates the L-lysine79 residue of histone H3 (H3K79), ultimately generating a trimethylated form. These modifications influence the binding of chromatin-associated proteins. This is the only known methylation event of a lysine residue within the core region of a histone, as all other such modifications occur at the tail.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3 S-adenosyl-L-methionine + a [histone H3]-L-lysine79
3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine79
S-adenosyl-L-methionine + a [histone H3]-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine79
S-adenosyl-L-methionine + a [histone H3]-N6,N6-dimethyl-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine79
S-adenosyl-L-methionine + a [histone H3]-N6-methyl-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine79
3 S-adenosyl-L-methionine + a [histone H3]-L-lysine79
3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine79
overall reaction
-
-
?
3 S-adenosyl-L-methionine + a [histone H3]-L-lysine79
3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine79
-
overall reaction
-
-
?
3 S-adenosyl-L-methionine + a [histone H3]-L-lysine79
3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine79
overall reaction
-
-
?
S-adenosyl-L-methionine + a [histone H3]-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine79
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine79
-
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine79
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-N6,N6-dimethyl-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine79
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-N6,N6-dimethyl-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine79
-
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-N6,N6-dimethyl-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine79
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-N6-methyl-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine79
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-N6-methyl-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine79
-
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3 S-adenosyl-L-methionine + a [histone H3]-L-lysine79
3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine79
S-adenosyl-L-methionine + a [histone H3]-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine79
S-adenosyl-L-methionine + a [histone H3]-N6,N6-dimethyl-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine79
S-adenosyl-L-methionine + a [histone H3]-N6-methyl-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine79
3 S-adenosyl-L-methionine + a [histone H3]-L-lysine79
3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine79
overall reaction
-
-
?
3 S-adenosyl-L-methionine + a [histone H3]-L-lysine79
3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine79
-
overall reaction
-
-
?
3 S-adenosyl-L-methionine + a [histone H3]-L-lysine79
3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine79
overall reaction
-
-
?
S-adenosyl-L-methionine + a [histone H3]-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine79
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine79
-
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine79
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-N6,N6-dimethyl-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine79
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-N6,N6-dimethyl-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine79
-
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-N6,N6-dimethyl-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine79
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-N6-methyl-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine79
-
-
-
?
S-adenosyl-L-methionine + a [histone H3]-N6-methyl-L-lysine79
S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine79
-
-
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
histone H2B lysine 120 ubiquitin
stimulates the enzyme activity. Ubiquitin binding reduces the enzyme's mobility on the nucleosome, allowing efficient higher methylation of histone H3 lysine 79
-
histone H2B ubiquitin
the enzyme activity is stimulated by histone H2B Lys120 ubiquitination
-
additional information
histone H2B lysine ubiquitination is required for enzyme activity
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
enzyme deletion impedes leukemia cell proliferation as well as switches exon skipping to the inclusion isoform in MLL-rearranged acute myeloid leukemia cell lines
malfunction
enzyme inhibition leads to increased sensitivity to chemotherapeutic agents and PARP inhibition
malfunction
enzyme knockdown reduces histone H3 lysine 79 methylation and N-Myc protein binding at the ODC1 and E2F2 gene promoters and reduces neuroblastoma cell proliferation
physiological function
enzyme-mediated histone H3 lysine 79 methylation likely functions in transcription via the recruitment of reader proteins which act directly or indirectly to affect RNA polymerase II activity. Aberrant transcriptional activation via histone H3 lysine 79 methylation by the enzyme is implicated in the development of leukemias
physiological function
enzyme-mediated methylation of [histone H3]-L-lysine79 is involved in the regulation of telomeric silencing, cell-cycle regulation, transcription elongation, DNA repair, cardiac function, embryonic development, erythropoiesis, and leukemia. Enzyme-mediated methylation of histone H3 lysine79 on the HOXA9 promoter contributes to increased expression of Hoxa9 in acute myeloid leukemia
physiological function
the enzyme is necessary for C/EBPbeta to promote gene expression in ovarian cancer cells. The promotional effect of C/EBPbeta on cisplatin resistance of tumor cells is mediated by the enzyme
physiological function
the enzyme is required for mixed lineage leukemia-AF9 (MLL-AF9) leukemogenesis. The degree of enzyme recruitment to MLL-AF9 defines the level of hematopoietic transformation
physiological function
the enzyme is required for MYCN-amplified neuroblastoma cell proliferation
physiological function
the enzyme is the major regulator in mediating skipping exon in MLL-rearranged acute myeloid leukemia progression
physiological function
the enzyme plays an important role in an early DNA damage response and repair of DNA double-strand breaks via the homologous recombination pathway
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). DOT1L_HUMAN
1537
0
164856
Swiss-Prot
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
F326A
I290A
the mutant shows significantly decreased enzyme activity compared to the wild type
I290D
the mutation abrogates the stimulation of enzyme activity L by histone H2B lysine 120 ubiquitin
L284A
the mutant shows significantly decreased enzyme activity compared to the wild type
L322D
the mutation abrogates the stimulation of enzyme activity L by histone H2B lysine 120 ubiquitin
R278E/R282E
the mutant shows a significant decrease in both di- and trimethylation of histone H3 lysine 79 compared to the wild type enzyme
R282A
the mutant shows dramatically decreased enzyme activity compared to the wild type
F326A
the mutant shows significantly decreased enzyme activity compared to the wild type
F326A
the mutation abrogates the stimulation of enzyme activity L by histone H2B lysine 120 ubiquitin
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
glutahione S-transferase affinity column chromatography, cation exchange chromatography and S200 gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
after a 48 h treatment with transforming growth factor beta1, the enzyme expression is decreased at the mRNA and protein levels
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
high levels of enzyme gene expression in human neuroblastoma tissues independently predict poor patient prognosis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Zhang, W.; Xia, X.; Jalal, D.I.; Kuncewicz, T.; Xu, W.; Lesage, G.D.; Kone, B.C.
Aldosterone-sensitive repression of ENaCalpha transcription by a histone H3 lysine-79 methyltransferase
Am. J. Physiol. Cell Physiol.
290
C936-C946
2006
Homo sapiens, Mus musculus
Wood, K.; Tellier, M.; Murphy, S.
DOT1L and H3K79 methylation in transcription and genomic stability
Biomolecules
8
E11
2018
Homo sapiens (Q8TEK3)
Wong, M.; Tee, A.E.L.; Milazzo, G.; Bell, J.L.; Poulos, R.C.; Atmadibrata, B.; Sun, Y.; Jing, D.; Ho, N.; Ling, D.; Liu, P.Y.; Zhang, X.D.; Huettelmaier, S.; Wong, J.W.H.; Wang, J.; Polly, P.; Perini, G.; Scarlett, C.J.; Liu, T.
The histone methyltransferase DOT1L promotes neuroblastoma by regulating gene transcription
Cancer Res.
77
2522-2533
2017
Homo sapiens (Q8TEK3)
Kuntimaddi, A.; Achille, N.J.; Thorpe, J.; Lokken, A.A.; Singh, R.; Hemenway, C.S.; Adli, M.; Zeleznik-Le, N.J.; Bushweller, J.H.
Degree of recruitment of DOT1L to MLL-AF9 defines level of H3K79 di- and tri-methylation on target genes and transformation potential
Cell Rep.
11
808-820
2015
Homo sapiens (Q8TEK3), Homo sapiens
Kari, V.; Raul, S.K.; Henck, J.M.; Kitz, J.; Kramer, F.; Kosinsky, R.L.; Uebelmesser, N.; Mansour, W.Y.; Eggert, J.; Spitzner, M.; Najafova, Z.; Bastians, H.; Grade, M.; Gaedcke, J.; Wegwitz, F.; Johnsen, S.A.
The histone methyltransferase DOT1L is required for proper DNA damage response, DNA repair, and modulates chemotherapy responsiveness
Clin. Epigenetics
11
4-4
2019
Homo sapiens (Q8TEK3)
Evanno, E.; Godet, J.; Piccirilli, N.; Guilhot, J.; Milin, S.; Gombert, J.; Fouchaq, B.; Roche, J.
Tri-methylation of H3K79 is decreased in TGF-beta1-induced epithelial-to-mesenchymal transition in lung cancer
Clin. Epigenetics
9
80
2017
Homo sapiens (Q8TEK3)
Jang, S.; Kang, C.; Yang, H.S.; Jung, T.; Hebert, H.; Chung, K.Y.; Kim, S.J.; Hohng, S.; Song, J.J.
Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase
Genes Dev.
33
620-625
2019
Homo sapiens (Q8TEK3)
Li, T.; Liu, Q.; Garza, N.; Kornblau, S.; Jin, V.
Integrative analysis reveals functional and regulatory roles of H3K79me2 in mediating alternative splicing
Genome Med.
10
30
2018
Homo sapiens (Q8TEK3)
Valencia-Sanchez, M.I.; De Ioannes, P.; Wang, M.; Vasilyev, N.; Chen, R.; Nudler, E.; Armache, J.P.; Armache, K.J.
Structural basis of Dot1L stimulation by histone H2B lysine 120 ubiquitination
Mol. Cell
74
1010-1019
2019
Homo sapiens (Q8TEK3)
Farooq, Z.; Banday, S.; Pandita, T.; Altaf, M.
The many faces of histone H3K79 methylation
Mutat. Res. Rev. Mutat. Res.
768
46-52
2016
Saccharomyces cerevisiae (Q04089), Homo sapiens (Q8TEK3)
Liu, D.; Zhang, X.X.; Li, M.C.; Cao, C.H.; Wan, D.Y.; Xi, B.X.; Tan, J.H.; Wang, J.; Yang, Z.Y.; Feng, X.X.; Ye, F.; Chen, G.; Wu, P.; Xi, L.; Wang, H.; Zhou, J.F.; Feng, Z.H.; Ma, D.; Gao, Q.L.
C/EBPbeta enhances platinum resistance of ovarian cancer cells by reprogramming H3K79 methylation
Nat. Commun.
9
1739
2018
Homo sapiens (Q8TEK3)
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