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PKMTs methylate histone lysines
Stable Identifier
R-HSA-3214841
DOI
10.3180/REACT_268728.2
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Chromatin organization (Homo sapiens)
Chromatin modifying enzymes (Homo sapiens)
PKMTs methylate histone lysines (Homo sapiens)
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Lysine methyltransferases (KMTs) and arginine methyltransferases (RMTs) have a common mechanism of catalysis. Both families transfer a methyl group from a common donor, S-adenosyl-L-methionine (SAM), to the nitrogen atom on the epsilon-amino group of lysine or arginine (Smith & Denu 2009) using a bimolecular nucleophillic substitution (SN2) methyl transfer mechanism (Smith & Denu 2009, Zhang & Bruice 2008). All human KMTs except DOT1L (KMT4) (Feng et al. 2002, van Leeuwen et al. 2002, Lacoste et al. 2002) have a ~130 amino acid catalytic domain referred to as the SET domain (Del Rizzo & Trievel 2011, Dillon et al. 2005, Herz et al. 2013).
Some KMTs selectively methylate a particular lysine residue on a specific histone type. The extent of this methylation (mono-, di- or tri-methylation) also can be stringent (Herz et al. 2013, Copeland et al. 2009). Many KMTs also have non-histone substrates (Herz et al 2013), which are not discussed in this module.
The coordinates of post-translational modifications represented and described here follow UniProt standard practice whereby coordinates refer to the translated protein before any processing. Histone literature typically refers to specific residues by numbers which are determined after the initiating methionine has been removed. Therefore the coordinates of post-translated residues in the Reactome database and described here are frequently +1 when compared to the histone literature.
SET domain-containing proteins are classified in one of 7 families (Dillon et al. 2005). First to be discovered were the SUV39 family named after founding member SUV39H1 (KMT1A), which selectively methylates lysine-10 of histone H3 (H3K9) (Rea et al. 2000). Family member EHMT2 (KMT1C, G9A) is the predominant H3K9 methyltransferase in mammals (Tachibana et al. 2002). SETDB1 (KMT1E, ESET) also predominantly methylates H3K9, most effectively when complexed with ATF7IP (MCAF, hAM) (Wang et al. 2003).
SETD2 (KMT3A, HYPB), a member of the SET2 family, specifically methylates histone H3 lysine-37 (H3K36) (Sun et al. 2005). WHSC1 (KMT3G, NSD2, MMSET) a member of the same family, targets H3K36 when provided with nucleosome substrates but also can methylate histone H4 lysine-45 when octameric native or recombinant nucleosome substrates are provided (Li et al. 2009); dimethylation of histone H3 at lysine-37 (H3K36me2) is thought to be the principal chromatin-regulatory activity of WHSC1 (Kuo et al. 2011). Relatives NSD1 (KMT3B) and WHSC1L1 (KMT3F, NSD3) also methylate nucleosomal H3K36. NSD1 is active on unmethylated or a mimetic monomethylated H3K36, but not di- or trimethylated H3K36 mimetics (Li et al. 2009). Human SETD7 (KMT7, SET7/9), not classified within the 7 SET-domain containing families, mono-methylates lysine-5 of histone H3 (H3K4) (Xiao et al. 2003).
Literature References
PubMed ID
Title
Journal
Year
11893494
Histone methylation in transcriptional control
Kouzarides, T
Curr. Opin. Genet. Dev.
2002
19721445
Protein methyltransferases as a target class for drug discovery
Richon, VM
,
Copeland, RA
,
Solomon, ME
Nat Rev Drug Discov
2009
Participants
Events
SETD3, SETD7 (KMT7), WHSC1L1 (KMT3F), Core MLL complex methylate lysine-5 of histone H3 (H3K4)
(Homo sapiens)
WHSC1L1 (KMT3F), Core MLL complex, SMYD3 (KMT3E) methylate methyl-lysine-5 of histone H3 (H3K4)
(Homo sapiens)
Core MLL complex, SMYD3, PRDM9 methylate dimethyl-lysine-5 of histone H3 (H3K4)
(Homo sapiens)
EHMT1:EHMT2 (KMT1D:KMT1C) methylates lysine-10 of histone H3 (H3K9)
(Homo sapiens)
EHMT1:EHMT2 (KMT1D:KMT1C) methylates methyl-lysine-10 of histone H3 (H3K9)
(Homo sapiens)
MECOM (KMT8E), PRDM16 (KMT8F) methylate lysine-10 of replicative histone H3 (H3K9)
(Homo sapiens)
SUV39H1 (KMT1A), SUV39H2 (KTM1B), SETDB1 (KMT1E), SETDB2 (KMT1F) methylate dimethyl-lysine-10 of histone H3 (H3K9)
(Homo sapiens)
PRC2 (EZH2) Core:AEBP2 methylates lysine-28 of histone H3 (H3K27)
(Homo sapiens)
WHSC1 (KMT3G) methylates lysine-28 of histone H3 (H3K27)
(Homo sapiens)
WHSC1L1 (KMT3F) methylates methyl-lysine-28 of histone H3 (H3K27)
(Homo sapiens)
WHSC1L1 (KMT3F) methylates dimethyl-lysine-28 of histone H3 (H3K27)
(Homo sapiens)
WHSC1 (KMT3G), NSD1 (KMT3B), SMYD2 (KMT3C) methylate lysine-37 of histone H3 (H3K36)
(Homo sapiens)
WHSC1 (KMT3G), NSD1 (KMT3B), SMYD2 (KMT3C), ASH1L methylate methyl-lysine-37 of histone H3 (H3K36)
(Homo sapiens)
SETD2 (KMT3A) methylates dimethyl-lysine-37 of histone H3 (H3K36)
(Homo sapiens)
ATF7IP binds SETDB1
(Homo sapiens)
DOT1L (KMT4) methylates lysine-80 of histone H3 (H3K79)
(Homo sapiens)
DOT1L (KMT4) methylates methyl-lysine-80 of histone H3 (H3K79)
(Homo sapiens)
DOT1L (KMT4) methylates dimethyl-lysine-80 of histone H3 (H3K79)
(Homo sapiens)
SETD8 (KMT5A) methylates lysine-21 of histone H4 (H4K20)
(Homo sapiens)
SUV420H1 (KMT5B), SUV420H2 (KMT5C), (possibly SMYD3 (KMT3E)) methylate methyl-lysine-21 of histone H4 (H4K20)
(Homo sapiens)
SUV420H1, SUV420H2, (possibly SMYD3 (KMT3E)) methylate dimethyl-lysine-21 of histone H4 (H4K20)
(Homo sapiens)
SETD6 methylates RELA in the NFkB complex
(Homo sapiens)
Participates
as an event of
Chromatin modifying enzymes (Homo sapiens)
Orthologous Events
PKMTs methylate histone lysines (Bos taurus)
PKMTs methylate histone lysines (Caenorhabditis elegans)
PKMTs methylate histone lysines (Canis familiaris)
PKMTs methylate histone lysines (Danio rerio)
PKMTs methylate histone lysines (Dictyostelium discoideum)
PKMTs methylate histone lysines (Drosophila melanogaster)
PKMTs methylate histone lysines (Gallus gallus)
PKMTs methylate histone lysines (Mus musculus)
PKMTs methylate histone lysines (Plasmodium falciparum)
PKMTs methylate histone lysines (Rattus norvegicus)
PKMTs methylate histone lysines (Saccharomyces cerevisiae)
PKMTs methylate histone lysines (Schizosaccharomyces pombe)
PKMTs methylate histone lysines (Sus scrofa)
Authored
Jupe, S (2013-03-12)
Reviewed
Motamedi, M (2014-11-17)
Created
Jupe, S (2013-03-12)
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