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
HSA84444(DOT1L)
PTR455566(DOT1L)
PPS100969530(DOT1L)
GGO101134931(DOT1L)
PON100450564(DOT1L)
NLE100587281 100606063(DOT1L)
MCC710033(DOT1L)
MCF101926502(DOT1L)
MTHB126942460
CSAB103233645(DOT1L)
CATY105591743(DOT1L)
PANU101006747(DOT1L)
TGE112612802(DOT1L)
RRO104671393(DOT1L)
RBB108531435(DOT1L)
TFN117073985(DOT1L)
PTEH111520730(DOT1L)
CJC100407532(DOT1L)
SBQ101038132(DOT1L)
CSYR103267705(DOT1L)
MMUR105860741(DOT1L)
LCAT123633033(DOT1L)
OGA100943444(DOT1L)
MMU208266(Dot1l)
MCAL110302935(Dot1l)
MPAH110326191(Dot1l)
RNO362831(Dot1l)
MCOC116076571(Dot1l)
MUN110555618(Dot1l)
CGE100771005(Dot1l)
MAUA101827360(Dot1l)
PLEU114686509(Dot1l)
MORG121459335(Dot1l)
MFOT126489209
AAMP119804509(Dot1l)
NGI103737299(Dot1l)
HGL101712712(Dot1l)
CPOC100713595(Dot1l)
CCAN109689927 109689929(Dot1l)
DORD105990338(Dot1l)
DSP122122869(Dot1l)
NCAR124968797
OPI101536127(DOT1L)
TUP102494943(DOT1L)
CFA485073(DOT1L)
CLUD112666222(DOT1L)
VVP112935591(DOT1L)
VLG121495589(DOT1L)
AML100464435(DOT1L)
UMR103681799(DOT1L)
UAH113242759(DOT1L)
UAR123793993(DOT1L)
ELK111161651 111161720
LLV125088548
MPUF101684140(DOT1L)
ORO101366843(DOT1L)
EJU114226156(DOT1L)
ZCA113916359(DOT1L)
MLX118005686(DOT1L)
NSU110593857(DOT1L)
FCA101101194(DOT1L)
PYU121021471(DOT1L)
PBG122486637(DOT1L)
LRUF124522929
PTG102966497(DOT1L)
PPAD109257714(DOT1L)
AJU106983698(DOT1L)
HHV120242313(DOT1L)
BTA510442(DOT1L)
BOM102280735(DOT1L)
BIU109561797(DOT1L)
BBUB102405560(DOT1L)
CHX102180119(DOT1L)
OAS101121261(DOT1L)
ODA120864760(DOT1L)
CCAD122440167(DOT1L)
SSC100738665(DOT1L)
CFR106729841(DOT1L)
CBAI105078365(DOT1L)
CDK105103623(DOT1L)
VPC102542063
BACU103011331(DOT1L)
LVE103083056(DOT1L)
OOR101281886(DOT1L)
DLE111166180(DOT1L)
PCAD102996362(DOT1L)
PSIU116752059(DOT1L)
ECB100068506(DOT1L)
EPZ103543191
EAI106834163(DOT1L)
MYB102240787(DOT1L)
MYD102773641(DOT1L)
MMYO118658025(DOT1L)
MLF102433201(DOT1L)
MNA107534598(DOT1L)
PKL118711157(DOT1L)
HAI109390613(DOT1L)
DRO112312198(DOT1L)
SHON118984445(DOT1L)
AJM119043705(DOT1L)
PDIC114502661(DOT1L)
PHAS123813761(DOT1L)
MMF118643514(DOT1L)
RFQ117037866(DOT1L)
PALE102893368(DOT1L)
PGIG120583726(DOT1L)
PVP105300457(DOT1L)
RAY107520102(DOT1L)
MJV108393233(DOT1L)
TOD119240531(DOT1L)
SARA101542520(DOT1L)
LAV100661109(DOT1L)
TMU101350137
DNM101427615(DOT1L)
MDO100619840(DOT1L)
GAS123243886(DOT1L)
SHR100918350(DOT1L)
PCW110223514(DOT1L)
OAA100088528(DOT1L)
GGA420078(DOT1L)
PCOC116235866(DOT1L)
MGP100546682(DOT1L)
CJO107325391(DOT1L)
NMEL110388996(DOT1L)
APLA101804645(DOT1L)
ACYG106045654(DOT1L)
AFUL116498985(DOT1L)
TGU100222310(DOT1L)
LSR110469481(DOT1L)
SCAN103821998(DOT1L)
PMOA120496392(DOT1L)
OTC121345945(DOT1L)
PRUF121353371(DOT1L)
GFR102036723(DOT1L)
FAB101807609(DOT1L)
PHI102108358(DOT1L)
PMAJ107215544(DOT1L)
CCAE111940168(DOT1L)
CCW104696943(DOT1L)
CBRC103620743(DOT1L)
ETL114071249(DOT1L) 114071752
ZAB102074377(DOT1L)
ACHL103797684
FPG101911291(DOT1L)
FCH102053275(DOT1L)
CLV102097756(DOT1L)
EGZ104131107(DOT1L)
NNI104009661(DOT1L)
PLET104620532(DOT1L)
PCRI104035670(DOT1L)
PCAO104042665(DOT1L)
ACUN113489497(DOT1L)
TALA104363231(DOT1L)
PADL103921169(DOT1L)
AFOR103903641(DOT1L)
ACHC115349672(DOT1L)
HALD104324695(DOT1L)
CCRI104162767(DOT1L)
CSTI104556762(DOT1L)
EHS104508566(DOT1L)
CMAC104476603(DOT1L)
MUI104545131(DOT1L)
FGA104083090(DOT1L)
GSTE104255223(DOT1L)
LDI104352503(DOT1L)
MNB103782145
OHA104329413(DOT1L)
NNT104404199(DOT1L)
DPUB104300751(DOT1L)
PGUU104461583(DOT1L)
ACAR104524443(DOT1L)
AVIT104278880(DOT1L)
CVF104286459(DOT1L)
CUCA104060963(DOT1L)
AAM106489522 106489524
AROW112971271(DOT1L)
NPD112952684(DOT1L)
TGT104564488(DOT1L)
DNE112991567(DOT1L)
SCAM104150642(DOT1L)
ASN102368409(DOT1L)
AMJ102567829(DOT1L)
CPOO109324920(DOT1L)
GGN109294827(DOT1L)
PSS102455080(DOT1L)
CMY102943895(DOT1L)
CPIC101947542(DOT1L)
TST117869110(DOT1L)
CABI116824481(DOT1L)
MRV120391639(DOT1L)
ACS103282705(dot1l)
PVT110072436(DOT1L) 110072437
SUND121937052(DOT1L)
PBI103061368(DOT1L)
PMUR107282186(DOT1L)
CTIG120301364(DOT1L)
TSR106548138(DOT1L) 106555419
PGUT117677503(DOT1L)
VKO123035334(DOT1L)
PMUA114588420(DOT1L)
ZVI118085936(DOT1L)
GJA107122041(DOT1L)
STOW125432967(DOT1L)
XLA108706873(dot1l.S) 108712856(dot1l.L)
XTR100497594(dot1l)
NPR108801355
RTEM120913393(DOT1L)
BBUF120989505(DOT1L)
BGAR122919790(DOT1L)
DRE559945(dot1l)
SRX107719574 107729667
SANH107655195 107676944
SGH107586394 107593341
CCAR109047010(dot1l) 109047583 109071951 109099236
CAUA113039587 113064939 113077116
PPRM120495223(dot1l)
MAMB125263799(dot1l)
IPU108270738(dot1l)
PHYP113547045(dot1l)
SMEO124391641(dot1l)
TFD113646121(dot1l)
AMEX103023208(dot1l)
EEE113582386(dot1l)
TRU101062350(dot1l)
TNGGSTEN00007367G001
LCO104918483(dot1l)
NCC104968234
CGOB115006711(dot1l)
ELY117253533(dot1l)
EFO125895418(dot1l)
PLEP121938762(dot1l)
SLUC116063452(dot1l)
ECRA117951070(dot1l)
ESP116695108(dot1l)
PFLV114561070(dot1l)
GAT120823388(dot1l)
PPUG119216789(dot1l)
MSAM119900868(dot1l) 119918779
CUD121512146(dot1l)
ALAT119028445(dot1l)
MZE101473918(dot1l)
ONL100700031(dot1l)
OAU116310046(dot1l)
OLA101166952(dot1l)
OML112137065(dot1l)
XMA102227320(dot1l)
XCO114151376(dot1l)
XHE116725679(dot1l)
PRET103463635(dot1l)
PFOR103155506(dot1l) 103155507
PLAI106950711(dot1l)
PMEI106908766(dot1l) 106920479
GAF122839040(dot1l)
CVG107089710(dot1l)
CTUL119779405(dot1l)
GMU124873360(dot1l)
NFU107397320(dot1l)
KMR108230786(dot1l)
ALIM106515034 106534283(dot1l)
NWH119430709(dot1l)
AOCE111566583(dot1l)
MCEP125009262(dot1l)
CSEM103376710(dot1l)
POV109625401 109645771
SSEN122780557(dot1l)
HHIP117759933(dot1l)
HSP124854783(dot1l)
LCF108877359
SDU111232114(dot1l)
SLAL111656359(dot1l)
XGL120790488(dot1l)
HCQ109532198(dot1l)
BPEC110174051(dot1l)
MALB109973059(dot1l)
BSPL114853611(dot1l)
SASA106584426 106613781(dot1l)
STRU115158259 115192618
OTW112233976 112250978
OMY110521445 110524305
OGO123997071 124037046
ONE115108316 115144895
SALP111972106 111975388
SNH120052441 120054782
CCLU121533519 121540357
ELS105011570(dot1l)
SFM108919875(dot1l)
PKI111860240(dot1l)
AANG118225430(dot1l) 118229550
LOC102690905(dot1l)
PSPA121301374 121301560
ARUT117401515 117428812
LCM102351844(DOT1L)
CMK103181918(dot1l)
RTP109926363(dot1l)
BFO118431258
BBEL109486044
CIN100178360
SCLV120336220
SPU100891935
APLC110985151
SKO100366496
DMEDmel_CG42803(gpp)
DER6553084
DSE6614114
DSIDsimw501_GD19874(Dsim_GD19874)
DYADyak_GE10220
DAN6501137
DSR110191935
DPO4802292
DPE6592037
DMN108155537
DWI6650725
DGR6564115
DMODmoj_GI23014
DAZ108621847
DNV108658160
DHE111599591
DVI6630054
CCAT101461338
BOD106622568
RZE108354426 108361828
MDE101896384
SCAC106090482
LCQ111675997
LSQ119607774
AGAAgaP_AGAP003282
ACOZ120953660
AARA120895460
ASTE118502766
AAG5579940
AALB109414131
CQUCpipJ_CPIJ001411
CPII120422365
CNS116343114
BCOO119084023
AME411070
ACER107996589
ALAB122714994
BIM100744223
BBIF117205381
BVK117238770
BVAN117157515
BTER100650198
BPYO122567651
CCAL108624642
OBB114878501
MGEN117219356
NMEA116423977
CGIG122398821
SOC105202538
MPHA105837416
AEC105144095
ACEP105624533
PBAR105433651
VEM105557690
HST105185248
DQU106744240
CFO105249170
FEX115246091
LHU105667327
PGC109860719
OBO105280498
PCF106791869
PFUC122522397
VPS122636599
NVI100116648
CSOL105366020
TPRE106648030
MDL103568612
CGLO123259854
FAS105267838
DAM107037952
AGIF122858557
CCIN107268991
TCA660658
DPA109540967 109542323
SOY115880425
ATD109595466
CSET123322437
AGB108912420
LDC111513763
NVL108567082
APLN108743108
PPYR116166100
OTU111414151
BMOR101736339
BMAN114246636
MSEX115444971
DPLKGM_201750
BANY112054178
NIQ126768173
PMAC106708949
PXU106123890
PRAP110994938
ZCE119829366
HAW110380490
HZE124633853
TNL113496303
SLIU111353544
OFU114364385
PXY105387142
API100168129
DNX107162006
AGS114125081 114125093 114125095
RMD113550627
BTAB109040566
CLEC106667972 106671086
HHAL106684978 106688078
NLU111046533
PHUPhum_PHUM478060
FOC113205719
TPAL117642722
ZNE110835135
CSEC111863535
FCD110859850
DPXDAPPUDRAFT_198981 DAPPUDRAFT_47843
DMK116917904
PVM113817809
PJA122255818
PCHN125035042
HAME121873236
PCLA123760254
PTRU123501673
HAZT108678295
EAF111704635
LSM121119474
PPOI119111187 119111189
ISCIscW_ISCW021226
DSV119433513
RSAN119405234
RMP119183477
VDE111244614
VJA111266166
TUT107359774
DPTE113794923
DFR124493566
CSCU111629121 111630420 111639298
PTEP107437400
SDM118187426
CELCELE_F54F7.7(dot-1.2) CELE_F55G7.2(dot-1.4) CELE_W06D11.4(dot-1.3) CELE_Y39G10AR.18(dot-1.1)
CBRCBG_03979 CBG_26504
LOALOAG_17417
NAINECAME_11271
TSPTsp_05196
HROHELRODRAFT_65325 HELRODRAFT_74931
LGILOTGIDRAFT_220459
PCAN112573676
BGT106067025
GAE121373924
HRF124114522
HRJ124284037
CRG105340311
MYI110440609
PMAX117325477
OBI106875466 106879336
OSN115223970
LAK106164636
SMMSmp_165000
SHXMS3_00008704(DOT1L_1)
OVIT265_14564
EGLEGR_04863
NVE5517386
EPA110244289
ATEN116287026
ADF107340719
AMIL114963056
PDAM113673214
SPIS111325641
DGT114530231
XEN124438976
HMG100211036
TADTRIADDRAFT_58052
AQU109584002
QSU112018118 112021480
SCEYDR440W(DOT1)
SEUBDI49_0608
SPAOSPAR_D06230
AGOAGOS_AER326C
ERCEcym_4091
KLAKLLA0_B01287g
KMXKLMA_40588(DOT1)
LTHKLTH0G04422g
VPOKpol_1004p44
ZROZYRO0D13200g
CGRCAGL0J10516g
NCSNCAS_0F01220(NCAS0F01220)
NDINDAI_0H01750(NDAI0H01750)
TPFTPHA_0D02550(TPHA0D02550)
TBLTBLA_0D01440(TBLA0D01440) TBLA_0E03030(TBLA0E03030)
TDLTDEL_0A04190(TDEL0A04190)
TGBHG536_0A05750
KAFKAFR_0I00880(KAFR0I00880)
KNGKNAG_0C03070(KNAG0C03070)
ZMKHG535_0D05220
PPAPAS_chr3_1133
DHADEHA2D01694g
PICPICST_41120
PGUPGUG_04903
SPAASPAPADRAFT_140015
LELLELG_02705
CALCAALFM_C306300WA(DOT1)
CTPCTRG_02231
COTCORT_0C04010
CDUCD36_86180
CTENCANTEDRAFT_115043
YLIYALI0E22715g
CLUCLUG_01248
CLUSA9F13_06g00440
CAURCJI97_000050
SLBAWJ20_173(DOT1)
PKZC5L36_0E04360
BBRXBRETT_005002
OPAHPODL_00709
NCRNCU06266
NTENEUTE1DRAFT146228(NEUTE1DRAFT_146228)
SMPSMAC_00083(putative dot1)
PANPODANSg5036
TTTTHITE_2119121
MTMMYCTH_2304605
CTHRCTHT_0026740
MGRMGG_05254
PPEIPpBr36_03635
TMNUCRPA7_5322
SSCKSPSK_07317
FGRFGSG_02567
FPUFPSE_08685
FVRFVEG_16524
FOXFOXG_10481
NHENECHADRAFT_70385
TRETRIREDRAFT_48225
TRRM419DRAFT_99879
MAWMAC_04133
MAJMAA_08905
CMTCCM_06781
PLJVFPFJ_04750
VALVDBG_10194
VDAVDAG_10394
CFJCFIO01_01877
CLUPCLUP02_02843
CHIGCH63R_02106
SAPOSAPIO_CDS2155
ELAUCREL1_8381
PFYPFICI_08108
SSLSS1G_03126
BFUBCIN_08g04180(Bcdot1)
MBEMBM_01079
PSCOLY89DRAFT_638470
GLZGLAREA_11312
ANIAN0091.2
AFMAFUA_5G12110
ACTACLA_015130
NFINFIA_075180
AORAO090120000327
ANGANI_1_296084(An09g02720)
AFVAFLA_009549
ALUCAKAW2_40325A(DOT1)
ACHEACHE_41229S(DOT1)
APUUAPUU_12067S(DOT1)
PCSPc21g07230
PDPPDIP_59550
TMFPMAA_031450
TRGTRUGW13939_05683
CIMCIMG_09225
CPWCPC735_016390
UREUREG_05056
PBLPAAG_02460
PBNPADG_05610
ABEARB_04392
TVETRV_03181
AJEHCAG_02616
BGHBDBG_07779
PNOSNOG_16009
PTEPTT_12191
BZECOCCADRAFT_98480
BSCCOCSADRAFT_116087
BORCOCMIDRAFT_97389
AALTCC77DRAFT_1026200
ZTRMYCGRDRAFT_23780(DOT2401)
PFJMYCFIDRAFT_202245 MYCFIDRAFT_80111
FFUCLAFUR5_02936 CLAFUR5_06494
BCOMBAUCODRAFT_32279
NPAUCRNP2_8424
TMLGSTUM_00007723001
CNECNK02230
CNBCNBK1310
CNGCNAG_01882
CGICGB_K1580W
TMSTREMEDRAFT_74374
TASAA1Q1_01745
PPLPOSPLDRAFT_96954
TVSTRAVEDRAFT_140731
DSQDICSQDRAFT_130599 DICSQDRAFT_90557
PCOPHACADRAFT_132924
SHSSTEHIDRAFT_106597
HIRHETIRDRAFT_479507
PSQPUNSTDRAFT_94330
ADLAURDEDRAFT_93731
FMEFOMMEDRAFT_107161
GTRGLOTRDRAFT_69490
LBCLACBIDRAFT_321307
CCICC1G_08658
ABPAGABI1DRAFT32345(AGABI1DRAFT_32345)
ABVAGABI2DRAFT190074(AGABI2DRAFT_190074)
MRRMoror_12676
MOREE1B28_009755
SCMSCHCO_02521437(SCHCODRAFT_02521437)
CPUTCONPUDRAFT_46848
SLASERLADRAFT_478945
WSEWALSEDRAFT_34014
WICJ056_001693
UMAUMAG_05545
PFPPFL1_05108
MGLMGL_1909
MRTMRET_1896
MSYMMSY001_1016
PGRPGTG_00890 PGTG_00895 PGTG_02618
MLRMELLADRAFT_92166
MBRMONBRDRAFT_34214
SREPTSG_04671
SPARSPRG_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

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