EC               Enzyme                                 

[histone H3]-trimethyl-L-lysine36 demethylase;
KDM4A (gene name);
KDM4B (gene name);
RPH1 (gene name);
JHDM3A (gene name);
JHDM3B (gene name);
JMJD2A (gene name);
JMJD2B (gene name)
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With 2-oxoglutarate as one donor, and incorporation of one atom of oxygen into each donor
[histone H3]-N6,N6,N6-trimethyl-L-lysine36,2-oxoglutarate:oxygen oxidoreductase
a [histone H3]-N6,N6,N6-trimethyl-L-lysine36 + 2 2-oxoglutarate + 2 O2 = a [histone H3]-N6-methyl-L-lysine36 + 2 succinate + 2 formaldehyde + 2 CO2 (overall reaction) [RN:R12459];
(1a) a [histone H3]-N6,N6,N6-trimethyl-L-lysine36 + 2-oxoglutarate + O2 = a [histone H3]-N6,N6-dimethyl-L-lysine36 + succinate + formaldehyde + CO2 [RN:R12460];
(1b) a [histone H3]-N6,N6-dimethyl-L-lysine36 + 2-oxoglutarate + O2 = a [histone H3]-N6-methyl-L-lysine36 + succinate + formaldehyde + CO2 [RN:R09510]
[histone H3]-N6,N6,N6-trimethyl-L-lysine36;
2-oxoglutarate [CPD:C00026];
O2 [CPD:C00007];
[histone H3]-N6,N6-dimethyl-L-lysine36
[histone H3]-N6-methyl-L-lysine36;
succinate [CPD:C00042];
formaldehyde [CPD:C00067];
CO2 [CPD:C00011];
[histone H3]-N6,N6-dimethyl-L-lysine36
Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated Lys36 residues in the tail of the histone protein H3 (H3K36). This lysine residue can exist in three methylation states (mono-, di- and trimethylated), but this group of enzymes only act on the the tri- and di-methylated forms. The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. Since trimethylation of H3K36 enhances transcription, this enzyme acts as a transcription repressor. The enzymes that possess this activity often also catalyse the activity of EC, [histone H3]-trimethyl-L-lysine9 demethylase. cf. EC, [histone H3]-dimethyl-L-lysine36 demethylase.
EC created 2019
K06709  [histone H3]-trimethyl-L-lysine9/36 demethylase
K19799  DNA damage-responsive transcriptional repressor / [histone H3]-trimethyl-L-lysine36 demethylase
HSA: 23030(KDM4B) 23081(KDM4C) 390245(KDM4E) 55693(KDM4D) 9682(KDM4A)
PTR: 451494 455614(KDM4B) 456829(KDM4A) 464989(KDM4C) 466754(KDM4D) 466755(KDM4E)
PPS: 100975218(KDM4B) 100979908(KDM4E) 100980259(KDM4D) 100981728(KDM4A) 100990982(KDM4C) 100992739
GGO: 101125373(KDM4A) 101132085(KDM4C) 101140323(KDM4D) 101144162 101145208(KDM4B) 115936314(KDM4E)
PON: 100172003(KDM4A) 100433788(KDM4C) 100443182(KDM4D) 100443556(KDM4E) 100449542 100457548(KDM4B)
NLE: 100582140 100586305 100587983 100589019(KDM4A) 100592056(KDM4C) 100597675(KDM4D) 100598260 115830958(KDM4B)
MCC: 695760(KDM4B) 698455(KDM4D) 700412 700765 701272(KDM4A) 715273(KDM4C)
MCF: 101926063(KDM4A) 102125576(KDM4B) 102136790(KDM4C) 102140298 102142534(KDM4D) 102144694(KDM4E)
CSAB: 103219465(KDM4C) 103224954(KDM4A) 103233733(KDM4B) 103248265(KDM4D) 103248269 103248270
RRO: 104657671(KDM4C) 104658622 104660268(KDM4D) 104660270(KDM4E) 104665479(KDM4B) 104669036(KDM4A)
RBB: 108512104(KDM4B) 108518738(KDM4C) 108535690(KDM4A) 108535741
CJC: 100387524 100388242 100389334(KDM4E) 100391630(KDM4C) 100406442(KDM4B) 100408074(KDM4D) 100411431(KDM4A)
SBQ: 101041165(KDM4B) 101045989(KDM4D) 101046833(KDM4E) 101053425(KDM4C) 101054213(KDM4A)
MMU: 193796(Kdm4b) 230674(Kdm4a) 244694(Kdm4d) 76804(Kdm4c)
MCAL: 110291915 110292899(Kdm4c) 110292914(Kdm4a) 110301432 110302014(Kdm4d) 110312705(Kdm4b)
MPAH: 110320880 110322808(Kdm4c) 110323167(Kdm4a) 110327601 110328486(Kdm4d) 110335468(Kdm4b)
RNO: 108348070 298144(Kdm4c) 301128(Kdm4b) 313539(Kdm4a) 500944(Kdm4dl2) 689582(Kdm4d)
MUN: 110546245(Kdm4b) 110547533(Kdm4d) 110547551 110552915(Kdm4a) 110565242
CGE: 100753944(Kdm4d) 100756054(Kdm4a) 100767737 100770247(Kdm4b) 100771667(Kdm4c)
HGL: 101698040(Kdm4c) 101698784 101698983 101707641(Kdm4d) 101715237(Kdm4a) 101718659(Kdm4b)
TUP: 102469253 102481449(KDM4B) 102486046(KDM4A) 102488334(KDM4C) 102492936(KDM4D)
CFA: 474704(KDM4C) 476741(KDM4B) 482530(KDM4A) 485120 485121(KDM4D)
VVP: 112914824(KDM4A) 112915836(KDM4D) 112915837 112921978(KDM4C) 112935617(KDM4B)
UMR: 103660769(KDM4D) 103660770 103662205(KDM4C) 103670808(KDM4A) 103681849(KDM4B)
UAH: 113242850(KDM4B) 113254782(KDM4A) 113259730 113260162(KDM4D) 113260620
ORO: 101369815(KDM4A) 101369880(KDM4B) 101379678(KDM4D) 101379961 101386926(KDM4C)
PTG: 102949786(KDM4C) 102950423(KDM4B) 102957193(KDM4D) 102957475 102967856(KDM4A)
PPAD: 109254791(KDM4A) 109255872(KDM4B) 109260118(KDM4C) 109267055 109267056 109267369(KDM4D)
AJU: 106970219(KDM4A) 106975455(KDM4B) 106984309(KDM4C) 106987083 106987092(KDM4D)
BTA: 107133150 508141(KDM4B) 512622(KDM4A) 524768 535671(KDM4C)
BOM: 102273176(KDM4C) 102275589(KDM4D) 102282048(KDM4B) 102284243(KDM4A)
BIU: 109556399(KDM4A) 109561725(KDM4B) 109562475(KDM4C) 109568776 109568777
BBUB: 102390095 102390765 102392239(KDM4A) 102402037(KDM4C) 102406406(KDM4B)
CHX: 102169067(KDM4A) 102170507(KDM4B) 102175575(KDM4C) 102185583 102185851(KDM4D)
SSC: 100514356 100621904(KDM4A) 100622077(KDM4C) 100627657 100738761(KDM4B)
CFR: 102505483(KDM4C) 102518341(KDM4A) 102523437(KDM4B) 102523511(KDM4D) 102523759
CDK: 105090903(KDM4A) 105091754(KDM4B) 105096552(KDM4D) 105098276(KDM4C) 105102910 105106725
BACU: 103003061(KDM4C) 103003890(KDM4A) 103011189(KDM4B) 103017228
ECB: 100053154(KDM4A) 100060699(KDM4C) 100062103(KDM4B) 100067390 100067461
EPZ: 103541685(KDM4B) 103546861 103546874 103557275(KDM4C) 103557419(KDM4A)
EAI: 106827478 106827509 106832335(KDM4B) 106837522(KDM4C) 106847916(KDM4A)
MYB: 102239838 102243828(KDM4B) 102246724 102252195(KDM4A) 102257879(KDM4C) 102261864(KDM4D)
MYD: 102755754 102757566(KDM4B) 102768643(KDM4D) 102769560(KDM4C) 102773056(KDM4A)
MNA: 107525662(KDM4B) 107526696(KDM4A) 107532354 107532356(KDM4D) 107538119(KDM4C)
HAI: 109383414(KDM4A) 109388603(KDM4B) 109390558(KDM4D) 109394570(KDM4C)
DRO: 112302738(KDM4C) 112312675(KDM4B) 112314479(KDM4A) 112317537 112317538
PALE: 102882553(KDM4A) 102892415 102897382(KDM4B) 102899019(KDM4C)
RAY: 107499501(KDM4A) 107510873(KDM4B) 107517665 107517666(KDM4D) 107519315(KDM4C)
MDO: 100018628(KDM4C) 100023921(KDM4B) 100025487(KDM4A)
SHR: 100920302(KDM4A) 100923927(KDM4B) 100930851(KDM4C)
PCW: 110197484(KDM4B) 110200215(KDM4A) 110221590(KDM4C)
OAA: 100077514(KDM4B) 100077720(KDM4A) 100681304(KDM4C)
GGA: 424571(KDM4A) 427231(KDM4C) 428354(KDM4B)
MGP: 100541123(KDM4B) 100544296(KDM4A) 100550263
NMEL: 110389067(KDM4B) 110389566(KDM4C) 110402235(KDM4A)
APLA: 101791399(KDM4C) 101799328(KDM4B) 101803199(KDM4A)
ACYG: 106034076(KDM4A) 106044969(KDM4B) 106046383(KDM4C)
TGU: 100219686(KDM4C) 100224169(KDM4A) 100225201(KDM4B)
LSR: 110469429(KDM4A) 110471241(KDM4C) 110477880(KDM4B)
SCAN: 103814958(KDM4A) 103819525(KDM4C) 103822070(KDM4B)
GFR: 102032085(KDM4B) 102039020(KDM4C) 102043301(KDM4A)
FAB: 101806204(KDM4B) 101811297(KDM4C) 101813754(KDM4A)
PHI: 102104087(KDM4A) 102109112(KDM4C) 102109691(KDM4B)
PMAJ: 107208042(KDM4A) 107215441(KDM4B) 107215920(KDM4C)
CCAE: 111933144(KDM4A) 111940625(KDM4C)
CCW: 104685185(KDM4C) 104695543(KDM4A) 104697400
ETL: 114056133(KDM4C) 114066015(KDM4A) 114067900(KDM4B)
FPG: 101912991(KDM4B) 101916030(KDM4A) 101918182(KDM4C)
FCH: 102046078(KDM4B) 102047870 102048418(KDM4A)
CLV: 102091977(KDM4A) 102092770(KDM4B) 102093362(KDM4C)
EGZ: 104124361(KDM4B) 104125526(KDM4A) 104125755(KDM4C)
NNI: 104015560(KDM4A) 104018736(KDM4B) 104021360(KDM4C)
ACUN: 113482983(KDM4A) 113489346(KDM4B) 113490378(KDM4C)
PADL: 103912179(KDM4B) 103920347(KDM4C) 103924079(KDM4A)
AAM: 106484490(KDM4B) 106484929(KDM4A) 106496770(KDM4C)
ASN: 102368582(KDM4B) 102377299(KDM4A) 102383020(KDM4C)
AMJ: 102571128(KDM4A) 106737064(KDM4C)
PSS: 102450770(KDM4C) 102458937(KDM4B) 102459587(KDM4A)
CMY: 102933803(KDM4C) 102937272(KDM4A) 102947631(KDM4B)
CPIC: 101943254(KDM4A) 101952792(KDM4B) 101953431(KDM4C)
ACS: 100551717(kdm4c) 100563051(kdm4b) 100566487(kdm4a)
PVT: 110073730(KDM4A) 110079264(KDM4B) 110088211(KDM4C)
PMUR: 107283446(KDM4A) 107299130(KDM4C)
TSR: 106540806(KDM4C) 106542258(KDM4A) 106555958
PMUA: 114588176(KDM4C) 114588484(KDM4B) 114599133(KDM4A)
GJA: 107109527(KDM4A) 107113915 107116117(KDM4C)
XTR: 100127653(kdm4c) 100135350(kdm4a) 394661(kdm4b)
NPR: 108789047(KDM4A) 108793106(KDM4C) 108796480
DRE: 100003413(kdm4aa) 334347(kdm4ab) 556504(kdm4b) 570194(kdm4c)
AMEX: 103024587 103028415 103030117(kdm4b) 103036954(kdm4a)
LCM: 102348735(KDM4B) 102351941(KDM4A) 102355951(KDM4C) 102365533
CMK: 103174610(kdm4a) 103183550(kdm4b) 103185468(kdm4c)
RTP: 109931349(kdm4a) 109935489
CIN: 100180205
SPU: 579470
APLC: 110985312
SKO: 100329036(Jmjd2c)
DME: Dmel_CG15835(Kdm4A) Dmel_CG33182(Kdm4B)
DSI: Dsimw501_GD10212(Dsim_GD10212)
AME: 726918
BIM: 100748259
BTER: 100648978
CCAL: 108628463
OBB: 114871125
MPHA: 105828504
AEC: 105143816
ACEP: 105626723
PBAR: 105432945
VEM: 105564383
HST: 105181802
DQU: 106750795
CFO: 105259589
LHU: 105675397
PGC: 109853913
OBO: 105279628
PCF: 106792706
NVI: 100124275
CSOL: 105362294
MDL: 103580058
TCA: 663231
ATD: 109602433
NVL: 108557278
BMOR: 100862759
BMAN: 114251842
PMAC: 106709641
PRAP: 110999090
HAW: 110382356
TNL: 113505720
DNX: 107161984
AGS: 114123066
RMD: 113553978
CLEC: 106674420
ZNE: 110833525
TUT: 107361997
DPTE: 113788484
PTEP: 107442880
CEL: CELE_Y48B6A.11(jmjd-2)
CBR: CBG20662(Cbr-jmjd-2)
BMY: Bm1_43520
PCAN: 112573289
CRG: 105346814
MYI: 110456629
OBI: 106883456
LAK: 106150433
SHX: MS3_07846
EGL: EGR_02504
NVE: 116614163
EPA: 110232595
ADF: 107335219
AMIL: 114952836
PDAM: 113674402
SPIS: 111325663
DGT: 114516485
HMG: 100210028
APRO: F751_2217
ERC: Ecym_3520
KMX: KLMA_30294(RPH1)
NCS: NCAS_0B04840(NCAS0B04840)
NDI: NDAI_0B02250(NDAI0B02250)
TDL: TDEL_0A01300(TDEL0A01300)
KAF: KAFR_0B02550(KAFR0B02550)
SPAR: SPRG_04576
 » show all
1  [PMID:16603238]
Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y
Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases.
Cell 125:467-81 (2006)
[hsa:9682] [cel:CELE_Y48B6A.11]
2  [PMID:16732292]
Klose RJ, Yamane K, Bae Y, Zhang D, Erdjument-Bromage H, Tempst P, Wong J, Zhang Y
The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36.
Nature 442:312-6 (2006)
3  [PMID:17525156]
Kim T, Buratowski S
Two Saccharomyces cerevisiae JmjC domain proteins demethylate histone H3 Lys36 in transcribed regions to promote elongation.
J Biol Chem 282:20827-35 (2007)
4  [PMID:17589523]
Couture JF, Collazo E, Ortiz-Tello PA, Brunzelle JS, Trievel RC
Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase.
Nat Struct Mol Biol 14:689-95 (2007)
5  [PMID:19061644]
Lin CH, Li B, Swanson S, Zhang Y, Florens L, Washburn MP, Abmayr SM, Workman JL
Heterochromatin protein 1a stimulates histone H3 lysine 36 demethylation by the Drosophila KDM4A demethylase.
Mol Cell 32:696-706 (2008)
6  [PMID:28743002]
Colmenares SU, Swenson JM, Langley SA, Kennedy C, Costes SV, Karpen GH
Drosophila Histone Demethylase KDM4A Has Enzymatic and Non-enzymatic Roles in Controlling Heterochromatin Integrity.
Dev Cell 42:156-169.e5 (2017)
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