KEGG   ENZYME: 2.1.1.360
Entry
EC 2.1.1.360                Enzyme                                 

Name
[histone H3]-lysine79 N-trimethyltransferase;
DOT1L (gene name);
KMT4 (gene name)
Class
Transferases;
Transferring one-carbon groups;
Methyltransferases
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)
(other) R03875 R04866 R04867
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
ec00310  Lysine degradation
ec01100  Metabolic pathways
Orthology
K11427  [histone H3]-lysine79 N-trimethyltransferase
Genes
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: 106729841(DOT1L)
CDK: 105103623(DOT1L)
BACU: 103011331(DOT1L)
LVE: 103083056(DOT1L)
OOR: 101281886(DOT1L)
DLE: 111166180(DOT1L)
PCAD: 102996362(DOT1L)
ECB: 100068506(DOT1L)
EPZ: 103543191
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)
NCC: 104968234
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)
BFO: 118431258
CIN: 100178360
SPU: 100891935
APLC: 110985151
SKO: 100366496
DME: Dmel_CG42803(gpp)
DER: 6553084
DSE: 6614114
DSI: Dsimw501_GD19874(Dsim_GD19874)
DAN: 6501137
DSR: 110191935
DPE: 6592037
DMN: 108155537
DWI: 6650725
DAZ: 108621847
DNV: 108658160
DHE: 111599591
DVI: 6630054
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
CSOL: 105366020
MDL: 103568612
TCA: 660658
ATD: 109595466
NVL: 108567082
BMOR: 101736339
BMAN: 114246636
PMAC: 106708949
PRAP: 110994938
HAW: 110380490
TNL: 113496303
PXY: 105387142
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
NVE: 5517386
EPA: 110244289
ADF: 107340719
AMIL: 114963056
PDAM: 113673214
SPIS: 111325641
DGT: 114530231
HMG: 100211036
AQU: 109584002
SCE: YDR440W(DOT1)
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)
CAL: CAALFM_C306300WA(DOT1)
SLB: AWJ20_173(DOT1)
NCR: NCU06266
NTE: NEUTE1DRAFT146228(NEUTE1DRAFT_146228)
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
ZTR: MYCGRDRAFT_23780(DOT2401)
CNE: CNK02230
CNB: CNBK1310
TASA: A1Q1_01745
ABP: AGABI1DRAFT32345(AGABI1DRAFT_32345)
ABV: AGABI2DRAFT190074(AGABI2DRAFT_190074)
MGL: MGL_1909
MRT: MRET_1896
SPAR: SPRG_11639
 » show all
Reference
1  [PMID:12123582]
  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
Curr Biol 12:1052-8 (2002)
DOI:10.1016/s0960-9822(02)00901-6
  Sequence
[hsa:84444]
Reference
2  [PMID:12080090]
  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
Genes Dev 16:1518-27 (2002)
DOI:10.1101/gad.1001502
  Sequence
[sce:YDR440W]
Reference
3  [PMID:12628190]
  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
Cell 112:711-23 (2003)
DOI:10.1016/s0092-8674(03)00114-4
  Sequence
[hsa:84444]
Reference
4  [PMID:18285465]
  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
Mol Cell Biol 28:2825-39 (2008)
DOI:10.1128/MCB.02076-07
  Sequence
[hsa:84444]
Other DBs
ExplorEnz - The Enzyme Database: 2.1.1.360
IUBMB Enzyme Nomenclature: 2.1.1.360
ExPASy - ENZYME nomenclature database: 2.1.1.360
BRENDA, the Enzyme Database: 2.1.1.360
LinkDB

DBGET integrated database retrieval system