Entry
Name
[histone H3]-lysine79 N-trimethyltransferase;
DOT1L (gene name);
KMT4 (gene name)
Class
Transferases;
Transferring one-carbon groups;
Methyltransferases
BRITE hierarchy
Sysname
S-adenosyl-L-methionine:[histone H3]-L-lysine79 N6-trimethyltransferase
Reaction(IUBMB)
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);
(1a) S-adenosyl-L-methionine + a [histone H3]-L-lysine79 = S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine79;
(1b) S-adenosyl-L-methionine + a [histone H3]-N6-methyl-L-lysine79 = S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine79;
(1c) 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
Reaction(KEGG)
Substrate
S-adenosyl-L-methionine [CPD:
C00019 ];
[histone H3]-L-lysine79;
[histone H3]-N6-methyl-L-lysine79;
[histone H3]-N6,N6-dimethyl-L-lysine79
Product
S-adenosyl-L-homocysteine [CPD:
C00021 ];
[histone H3]-N6,N6,N6-trimethyl-L-lysine79;
[histone H3]-N6-methyl-L-lysine79;
[histone H3]-N6,N6-dimethyl-L-lysine79
Comment
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.
History
EC 2.1.1.360 created 1976 as EC 2.1.1.43, modified 1982, modified 1983, part transferred 2019 to EC 2.1.1.360
Pathway
Orthology
K11427 [histone H3]-lysine79 N-trimethyltransferase
Genes
NLE : 100587281 100606063(DOT1L)
HMH : 116472185 116484129(DOT1L)
CCAN : 109689927 109689929(Dot1l)
ETL : 114071249(DOT1L) 114071752
PVT : 110072436(DOT1L) 110072437
TSR : 106548138(DOT1L) 106555419
XLA : 108706873(dot1l.S) 108712856(dot1l.L)
SANH : 107655195 107676944
CCAR : 109047010(dot1l) 109047583 109071951 109099236
CAUA : 113039587 113064939 113077116
CGIB : 127942988 127987341
MASI : 127437915 127439273
MSAM : 119900868(dot1l) 119918779
PFOR : 103155506(dot1l) 103155507
PMEI : 106908766(dot1l) 106920479
ALIM : 106515034 106534283(dot1l)
SASA : 106584426 106613781(dot1l)
STRU : 115158259 115192618
OKE : 118359228 118389810(dot1l)
SALP : 111972106 111975388
CCLU : 121533519 121540357
AANG : 118225430(dot1l) 118229550
PSPA : 121301374 121301560
ARUT : 117401515 117428812
DSI : Dsimw501_GD19874(Dsim_GD19874)
AGS : 114125081 114125093 114125095
CLEC : 106667972 106671086
HHAL : 106684978 106688078
DPX : DAPPUDRAFT_198981 DAPPUDRAFT_47843
PPOI : 119111187 119111189
CSCU : 111629121 111630420 111639298
CEL : CELE_F54F7.7(dot-1.2) CELE_F55G7.2(dot-1.4) CELE_W06D11.4(dot-1.3) CELE_Y39G10AR.18(dot-1.1)
CBR : CBG_03979 CBG_03980 CBG_26504
SHX : MS3_00008704(DOT1L_1)
NCS : NCAS_0F01220(NCAS0F01220)
NDI : NDAI_0H01750(NDAI0H01750)
TPF : TPHA_0D02550(TPHA0D02550)
TBL : TBLA_0D01440(TBLA0D01440) TBLA_0E03030(TBLA0E03030)
TDL : TDEL_0A04190(TDEL0A04190)
KAF : KAFR_0I00880(KAFR0I00880)
KNG : KNAG_0C03070(KNAG0C03070)
CAL : CAALFM_C306300WA(DOT1)
NTE : NEUTE1DRAFT146228(NEUTE1DRAFT_146228)
SMP : SMAC_00083(putative_dot1)
PBEL : QC761_0106140(DOT1)
FPOA : FPOAC1_002690(DOT1)
BFU : BCIN_08g04180(Bcdot1)
ZTR : MYCGRDRAFT_23780(DOT2401)
PFJ : MYCFIDRAFT_202245 MYCFIDRAFT_80111
FFU : CLAFUR5_02936 CLAFUR5_06494
CCAC : CcaHIS019_0606110(DOT1)
DSQ : DICSQDRAFT_130599 DICSQDRAFT_90557
ABP : AGABI1DRAFT32345(AGABI1DRAFT_32345)
ABV : AGABI2DRAFT190074(AGABI2DRAFT_190074)
SCM : SCHCO_02521437(SCHCODRAFT_02521437)
PGR : PGTG_00890 PGTG_00895 PGTG_02618
» show all
Taxonomy
Reference
Authors
Feng Q, Wang H, Ng HH, Erdjument-Bromage H, Tempst P, Struhl K, Zhang Y
Title
Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain.
Journal
Sequence
Reference
Authors
Ng HH, Feng Q, Wang H, Erdjument-Bromage H, Tempst P, Zhang Y, Struhl K
Title
Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association.
Journal
Sequence
Reference
Authors
Min J, Feng Q, Li Z, Zhang Y, Xu RM
Title
Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase.
Journal
Sequence
Reference
Authors
Steger DJ, Lefterova MI, Ying L, Stonestrom AJ, Schupp M, Zhuo D, Vakoc AL, Kim JE, Chen J, Lazar MA, Blobel GA, Vakoc CR
Title
DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells.
Journal
Sequence
Other DBs
ExPASy - ENZYME nomenclature database: 2.1.1.360
LinkDB
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