EC                Enzyme                                 

[histone H3]-lysine79 N-trimethyltransferase;
DOT1L (gene name);
KMT4 (gene name)
Transferring one-carbon groups;
BRITE hierarchy
S-adenosyl-L-methionine:[histone H3]-L-lysine79 N6-trimethyltransferase
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
S-adenosyl-L-methionine [CPD:C00019];
[histone H3]-L-lysine79;
[histone H3]-N6-methyl-L-lysine79;
[histone H3]-N6,N6-dimethyl-L-lysine79
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
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.
EC created 1976 as EC, modified 1982, modified 1983, part transferred 2019 to EC
ec00310  Lysine degradation
ec01100  Metabolic pathways
K11427  [histone H3]-lysine79 N-trimethyltransferase
HSA: 84444(DOT1L)
PTR: 455566(DOT1L)
PPS: 100969530(DOT1L)
GGO: 101134931(DOT1L)
PON: 100450564(DOT1L)
NLE: 100587281 100606063(DOT1L)
MCC: 710033(DOT1L)
MCF: 101926502(DOT1L)
CSAB: 103233645(DOT1L)
RRO: 104671393(DOT1L)
RBB: 108531435(DOT1L)
CJC: 100407532(DOT1L)
SBQ: 101038132(DOT1L)
MMU: 208266(Dot1l)
MCAL: 110302935(Dot1l)
MPAH: 110326191(Dot1l)
RNO: 362831(Dot1l)
MUN: 110555618(Dot1l)
CGE: 100771005(Dot1l)
NGI: 103737299(Dot1l)
HGL: 101712712(Dot1l)
CCAN: 109689927 109689929(Dot1l)
TUP: 102494943(DOT1L)
CFA: 485073(DOT1L)
VVP: 112935591(DOT1L)
AML: 100464435(DOT1L)
UMR: 103681799(DOT1L)
UAH: 113242759(DOT1L)
ORO: 101366843(DOT1L)
FCA: 101101194(DOT1L)
PTG: 102966497(DOT1L)
PPAD: 109257714(DOT1L)
AJU: 106983698(DOT1L)
BTA: 510442(DOT1L)
BOM: 102280735(DOT1L)
BIU: 109561797(DOT1L)
BBUB: 102405560(DOT1L)
CHX: 102180119(DOT1L)
OAS: 101121261(DOT1L)
SSC: 100738665(DOT1L)
CFR: 102522071(DOT1L) 106729841
CDK: 105103623(DOT1L)
BACU: 103011331(DOT1L)
LVE: 103083056(DOT1L)
OOR: 101281886(DOT1L)
DLE: 111166180(DOT1L)
PCAD: 102996362(DOT1L)
ECB: 100068506(DOT1L)
EPZ: 103543191 103544492(DOT1L)
EAI: 106834163(DOT1L)
MYB: 102240787(DOT1L)
MYD: 102773641(DOT1L)
MNA: 107534598(DOT1L)
HAI: 109390613(DOT1L)
DRO: 112312198(DOT1L)
PALE: 102893368(DOT1L)
RAY: 107520102(DOT1L)
MJV: 108393233(DOT1L)
LAV: 100661109(DOT1L)
TMU: 101350137
MDO: 100619840(DOT1L)
SHR: 100918350(DOT1L)
PCW: 110223514(DOT1L)
OAA: 100088528(DOT1L)
GGA: 420078(DOT1L)
MGP: 100546682(DOT1L)
CJO: 107325391(DOT1L)
NMEL: 110388996(DOT1L)
APLA: 101804645(DOT1L)
ACYG: 106045654(DOT1L)
TGU: 100222310(DOT1L)
LSR: 110469481(DOT1L)
SCAN: 103821998(DOT1L)
GFR: 102036723(DOT1L)
FAB: 101807609(DOT1L)
PHI: 102108358(DOT1L)
PMAJ: 107215544(DOT1L)
CCAE: 111940168(DOT1L)
CCW: 104696943(DOT1L)
ETL: 114071249(DOT1L) 114071752
FPG: 101911291(DOT1L)
FCH: 102053275(DOT1L)
CLV: 102097756(DOT1L)
EGZ: 104131107(DOT1L)
NNI: 104009661(DOT1L)
ACUN: 113489497(DOT1L)
PADL: 103921169(DOT1L)
ASN: 102368409(DOT1L)
AMJ: 102567829(DOT1L)
PSS: 102455080(DOT1L)
CMY: 102943895(DOT1L)
CPIC: 101947542(DOT1L)
ACS: 103282705(dot1l)
PVT: 110072436(DOT1L) 110072437
PBI: 103061368(DOT1L)
PMUR: 107282186(DOT1L)
TSR: 106548138(DOT1L) 106555419
PMUA: 114588420(DOT1L)
GJA: 107122041(DOT1L)
XLA: 108706873(dot1l.S) 108712856(dot1l.L)
XTR: 100497594(dot1l)
NPR: 108801355
DRE: 559945(dot1l)
IPU: 108270738(dot1l)
PHYP: 113547045(dot1l)
AMEX: 103023208(dot1l)
EEE: 113582386(dot1l)
TRU: 101062350(dot1l)
LCO: 104918483(dot1l)
MZE: 101473918(dot1l)
ONL: 100700031(dot1l)
OLA: 101166952(dot1l)
XMA: 102227320(dot1l)
XCO: 114151376(dot1l)
PRET: 103463635(dot1l)
CVG: 107089710(dot1l)
NFU: 107397320(dot1l)
KMR: 108230786(dot1l)
ALIM: 106515034 106534283(dot1l)
AOCE: 111566583(dot1l)
CSEM: 103376710(dot1l)
LCF: 108877359(dot1l)
SDU: 111232114(dot1l)
SLAL: 111656359(dot1l)
HCQ: 109532198(dot1l)
BPEC: 110174051(dot1l)
MALB: 109973059(dot1l)
SASA: 106584426 106613781(dot1l)
ELS: 105011570(dot1l)
SFM: 108919875(dot1l)
PKI: 111860240(dot1l)
LCM: 102351844(DOT1L)
CMK: 103181918(dot1l)
RTP: 109926363(dot1l)
CIN: 100178360
SPU: 100891935
APLC: 110985151
SKO: 100366496
DME: Dmel_CG42803(gpp)
DER: 6553084
DSI: Dsimw501_GD19874(Dsim_GD19874)
DSR: 110191935
DPE: 6592037
DMN: 108155537
DWI: 6650725
DAZ: 108621847
DNV: 108658160
DHE: 111599591
MDE: 101896384
LCQ: 111675997
AAG: 5579940
AALB: 109414131
AME: 411070
BIM: 100744223
BTER: 100650198
CCAL: 108624642
OBB: 114878501
SOC: 105202538
MPHA: 105837416
AEC: 105144095
ACEP: 105624533
PBAR: 105433651
VEM: 105557690
HST: 105185248
DQU: 106744240
CFO: 105249170
LHU: 105667327
PGC: 109860719
OBO: 105280498
PCF: 106791869
NVI: 100116648(Dot1l)
CSOL: 105366020
MDL: 103568612
TCA: 660658
ATD: 109595466
NVL: 108567082
BMOR: 101736339
BMAN: 114246636
PMAC: 106708949
PRAP: 110994938
HAW: 110380490
TNL: 113496303
API: 100168129
DNX: 107162006
RMD: 113550627
BTAB: 109040566
ZNE: 110835135
FCD: 110859850
PVM: 113817809
TUT: 107359774
DPTE: 113794923
PTEP: 107437400
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)
BMY: Bm1_56955
TSP: Tsp_05196
PCAN: 112573676
CRG: 105340311
MYI: 110440609
LAK: 106164636
SHX: MS3_09541
EGL: EGR_04863
EPA: 110244289
ADF: 107340719
AMIL: 114963056
PDAM: 113673214
SPIS: 111325641
DGT: 114530231
HMG: 100211036
AQU: 109584002
ERC: Ecym_4091
KMX: KLMA_40588(DOT1)
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)
SLB: AWJ20_173(DOT1)
NCR: NCU06266
SMP: SMAC_00083(putative dot1)
MGR: MGG_05254
SSCK: SPSK_07317
MAW: MAC_04133
MAJ: MAA_08905
CMT: CCM_06781
BFU: BCIN_08g04180(Bcdot1)
MBE: MBM_01079
ANI: AN0091.2
ANG: ANI_1_296084(An09g02720)
ABE: ARB_04392
TVE: TRV_03181
PTE: PTT_12191
CNE: CNK02230
MGL: MGL_1909
MRT: MRET_1896
SPAR: SPRG_11639
 » show all
1  [PMID:12123582]
Feng Q, Wang H, Ng HH, Erdjument-Bromage H, Tempst P, Struhl K, Zhang Y
Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET  domain.
Curr Biol 12:1052-8 (2002)
2  [PMID:12080090]
Ng HH, Feng Q, Wang H, Erdjument-Bromage H, Tempst P, Zhang Y, Struhl K
Lysine methylation within the globular domain of histone H3 by Dot1 is important  for telomeric silencing and Sir protein association.
Genes Dev 16:1518-27 (2002)
3  [PMID:12628190]
Min J, Feng Q, Li Z, Zhang Y, Xu RM
Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase.
Cell 112:711-23 (2003)
4  [PMID:18285465]
Steger DJ, Lefterova MI, Ying L, Stonestrom AJ, Schupp M, Zhuo D, Vakoc AL, Kim JE, Chen J, Lazar MA, Blobel GA, Vakoc CR
DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells.
Mol Cell Biol 28:2825-39 (2008)
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