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
BRITE hierarchy
[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(KDM4E) 101145208(KDM4B)
PON: 100172003(KDM4A) 100433788(KDM4C) 100443182(KDM4D) 100443556(KDM4E) 100449542 100457548(KDM4B)
NLE: 100582140 100586305 100587983 100589019(KDM4A) 100592056(KDM4C) 100597675(KDM4D) 100598260
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) 108525734 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) 104652776
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) 689582(Kdm4d)
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: 112913043 112914824(KDM4A) 112915836(KDM4D) 112915837 112921978(KDM4C) 112935617(KDM4B)
AML: 100467443(KDM4B) 100473204(KDM4A) 100475996(KDM4C) 100476158(KDM4D)
UMR: 103660769(KDM4D) 103660770 103662205(KDM4C) 103670808(KDM4A) 103681849(KDM4B)
ORO: 101369815(KDM4A) 101369880(KDM4B) 101379678(KDM4D) 101379961 101386926(KDM4C)
PTG: 102949786(KDM4C) 102950423(KDM4B) 102957193(KDM4D) 102957475 102967856(KDM4A)
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) 102283294 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)
OAS: 101103090 101103347 101110232(KDM4B) 101111840(KDM4A) 101117992(KDM4C)
SSC: 100514356 100621904(KDM4A) 100622077(KDM4C) 100627657 100738761(KDM4B)
BACU: 103003061(KDM4C) 103003890(KDM4A) 103011189(KDM4B) 103017228
ECB: 100053154(KDM4A) 100060699(KDM4C) 100062103(KDM4B) 100067390 100067461
EAI: 106827478 106827509 106832335(KDM4B) 106837522(KDM4C) 106847916(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) 107196611
RAY: 107499501(KDM4A) 107510873(KDM4B) 107517665 107517666(KDM4D) 107519315(KDM4C)
MDO: 100018628(KDM4C) 100023921(KDM4B) 100025487(KDM4A)
PCW: 110197484(KDM4B) 110200215(KDM4A) 110221590(KDM4C)
OAA: 100077514(KDM4B) 100077720(KDM4A)
GGA: 424571(KDM4A) 427231(KDM4C) 428354(KDM4B)
MGP: 100541123(KDM4B) 100544296(KDM4A)
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)
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) 106628634
PMAJ: 107208042(KDM4A) 107215441(KDM4B) 107215920(KDM4C)
CCAE: 111933144(KDM4A) 111940282(KDM4B) 111940625(KDM4C)
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: 102561727(KDM4B) 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) 110083700 110088211(KDM4C)
PMUR: 107283446(KDM4A) 107296147(KDM4B) 107299130(KDM4C) 107300567
PMUA: 114588176(KDM4C) 114588484(KDM4B) 114599133(KDM4A)
GJA: 107109527(KDM4A) 107113915 107116117(KDM4C)
XTR: 100127653(kdm4c) 100135350(kdm4a) 394661(kdm4b)
DRE: 100003413(kdm4aa) 334347(kdm4ab) 556504(kdm4b) 570194(kdm4c)
LCM: 102348735(KDM4B) 102351941(KDM4A) 102355951(KDM4C) 102365533
CMK: 103174610(kdm4a) 103183550(kdm4b) 103185468(kdm4c)
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
NVL: 108557278
BMOR: 100862759
PMAC: 106709641
PRAP: 110999090
HAW: 110382356
TNL: 113505720
CLEC: 106674420
ZNE: 110833525
TUT: 107361997
DPTE: 113788484
PTEP: 107442880
CEL: CELE_Y48B6A.11(jmjd-2)
CBR: CBG20662(Cbr-jmjd-2)
BMY: Bm1_43520
TSP: Tsp_10658
PCAN: 112573289
MYI: 110456629
LAK: 106150433
SHX: MS3_07846
EGL: EGR_02504
EPA: 110232595
ADF: 107335219
AMIL: 114952836
PDAM: 113674402
SPIS: 111325663
DGT: 114516485
AQU: 100631846
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)
MAW: MAC_07423
MAJ: MAA_00645
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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