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Information on EC 1.14.11.68 - [histone H3]-trimethyl-L-lysine27 demethylase
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1.14.11.68 [histone H3]-trimethyl-L-lysine27 demethylaseIUBMB Comments
Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated L-lysine residues at position 27 of histone H3 (H3K27). The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. They can act on tri- and di-methylated forms, but have no activity with the mono-methylated form.
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Word Map
- 1.14.11.68
-
kabuki
- chromatin
-
facial
- demethylases
-
intellectual
- pik3ca
-
arid1a
- crebbp
-
h3k4me3
-
polycomb
- medicine
-
muscle-invasive
-
smarca4
-
k-specific
- fat1
-
gestalt
- gsk-j4
The enzyme appears in viruses and cellular organisms
Reaction Schemes
Synonyms
kdm6a, lysine-specific demethylase 6b, lysine-specific demethylase 6a, jmjd-3.1, kdm6c, kdm6al, f18e9.5, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
JMJD3
KDM6A
KDM6B
KDM6C
-
-
-
-
UTX
UTY
-
-
-
-
JMJD3
-
-
-
-
KDM6A
-
-
-
-
UTX
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a [histone H3]-N6,N6,N6-trimethyl-L-lysine27 + 2 2-oxoglutarate + 2 O2 = a [histone H3]-N6-methyl-L-lysine27 + 2 succinate + 2 formaldehyde + 2 CO2
overall reaction
-
-
-
a [histone H3]-N6,N6,N6-trimethyl-L-lysine27 + 2-oxoglutarate + O2 = a [histone H3]-N6,N6-dimethyl-L-lysine27 + succinate + formaldehyde + CO2
(1a)
-
-
-
a [histone H3]-N6,N6-dimethyl-L-lysine27 + 2-oxoglutarate + O2 = a [histone H3]-N6-methyl-L-lysine27 + succinate + formaldehyde + CO2
(1b)
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
[histone H3]-N6,N6,N6-trimethyl-L-lysine27,2-oxoglutarate:oxygen oxidoreductase
Requires iron(II). This entry describes a group of enzymes that demethylate N-methylated L-lysine residues at position 27 of histone H3 (H3K27). The enzymes are dioxygenases and act by hydroxylating the methyl group, forming an unstable hemiaminal that leaves as formaldehyde. They can act on tri- and di-methylated forms, but have no activity with the mono-methylated form.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
a [histine H3]-N6,N6,N6-trimethyllysine27 + 2 2-oxoglutarate + 2 O2
a [histine H3]-N6-methyllysine27 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
?
a [histone H3]-N6,N6,N6-trimethyl-L-lysine27 + 2 2-oxoglutarate + 2 O2
a [histone H3]-N6-methyl-L-lysine27 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
?
a [histone H3]-N6,N6,N6-trimethyl-L-lysine27 + 2-oxoglutarate + O2
a [histone H3]-N6,N6-dimethyl-L-lysine27 + succinate + formaldehyde + CO2
-
-
-
?
a [histone H3]-N6,N6-dimethyl-L-lysine27 + 2-oxoglutarate + O2
a [histone H3]-N6-methyl-L-lysine27 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyl-L-lysine 27 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 27 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyllysine27 + 2 2-oxoglutarate + 2 O2
[histone H3]-N6-methyllysine27 + 2 succinate + 2 formaldehyde + 2 CO2
[histone H3]-N6,N6,N6-trimethyllysine27 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyllysine27 + succinate + formaldehyde + CO2
[histone H3]-N6,N6-dimethyl-L-lysine 27 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 27 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyllysine27 + 2-oxoglutarate + O2
[histone H3]-N6-methyllysine27 + succinate + formaldehyde + CO2
[histone H3]-N6-methyllysine27 + 2-oxoglutarate + O2
[histone H3]-lysine27 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyllysine27 + 2 2-oxoglutarate + 2 O2
[histone H3]-N6-methyllysine27 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyllysine27 + 2 2-oxoglutarate + 2 O2
[histone H3]-N6-methyllysine27 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyllysine27 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyllysine27 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyllysine27 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyllysine27 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyllysine27 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyllysine27 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyllysine27 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyllysine27 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyllysine27 + 2-oxoglutarate + O2
[histone H3]-N6-methyllysine27 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyllysine27 + 2-oxoglutarate + O2
[histone H3]-N6-methyllysine27 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyllysine27 + 2-oxoglutarate + O2
[histone H3]-N6-methyllysine27 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyllysine27 + 2-oxoglutarate + O2
[histone H3]-N6-methyllysine27 + succinate + formaldehyde + CO2
-
-
-
?
additional information
?
-
monomethylated histone H3K27 is a poor substrate. No substrates: methylated histone residues H3K4, H3K9, H3K36, H3K79, and H4K20
-
-
?
additional information
?
-
no substrates: methylated histone residues H3K4 and H3K9
-
-
?
additional information
?
-
UTX prefers H3K27me2 and H3K27me3 over H3K27me1 as substrates. No substrates: methylated histone residues H3K4, H3K9, and H3K36
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
[histone H3]-N6,N6,N6-trimethyl-L-lysine 27 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyl-L-lysine 27 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyllysine27 + 2 2-oxoglutarate + 2 O2
[histone H3]-N6-methyllysine27 + 2 succinate + 2 formaldehyde + 2 CO2
-
-
-
?
[histone H3]-N6,N6,N6-trimethyllysine27 + 2-oxoglutarate + O2
[histone H3]-N6,N6-dimethyllysine27 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyl-L-lysine 27 + 2-oxoglutarate + O2
[histone H3]-N6-methyl-L-lysine 27 + succinate + formaldehyde + CO2
-
-
-
?
[histone H3]-N6,N6-dimethyllysine27 + 2-oxoglutarate + O2
[histone H3]-N6-methyllysine27 + succinate + formaldehyde + CO2
-
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
GSKJ4
inhibitor is active against native and temozolomide-resistant glioblastoma cells, albeit at at a lower effcacy than JIB 04, inhibitor of lysine demethylase KDM5A, EC 1.14.11.67. GSK J4 and JIB 04 strongly synergize and are a potent combination against temozolomide-resistant glioblastoma cells. GSK J4 does not synergize with temozolomide
-
GSK-J4
both the mRNA and protein levels of mPR3 are significantly reduced compared to controls
GSK-J4
specific inhibitor, application dramatically suppresses Th17 cell differentiation in vitro
GSK-J4
specific inhibitor of the H3K27me3 histone demethylases UTX and JMJD3, inhibits herpes simplex virus HSV-1 reactivation from sensory neurons in vitro; specific inhibitor of the H3K27me3 histone demethylases UTX and JMJD3, inhibits herpes simplex virus HSV-1 reactivation from sensory neurons in vitro
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
expressed in macrophages in response to bacterial products and inflammatory cytokines
brenda
neutrophil JMJD3 expression is increased in patients with sepsis
brenda
additional information
UTX is selectively excluded from the HOX loci in embryonic stem cells, in which HOX genes are largely silent
brenda
at the blastula stage, Jmjd3, Utx and H3K27 methylase Ezh2 show similar expression patterns in the animal cap and marginal zone that give rise to the ectoderm and mesoderm, respectively. The three genes maintain similar expresxadsion patterns in the neural plate, preplacodal ectoderm and axial mesoderm during the gastrula and neurula stages. Later, expression is maintained in the developing brain and cranial sensory tissues, such as the eye and ear, of tailbud embryos
brenda
UTX is enriched around the transcription start sites of many HOX genes in primary human fibroblasts
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
embryonic fibroblasts display a dynamic nucleocytoplasmic shuttling of endogenous Jmjd3. Jmjd3 is localized both into the cytoplasm and the nucleus, and its nuclear export is dependent on exportin-1
brenda
nuclear localization of Jmjd3 is required for effective demethylation of H3K27me3. The N-terminal region of the protein is responsible for its nuclear placement
brenda
embryonic fibroblasts display a dynamic nucleocytoplasmic shuttling of endogenous Jmjd3. Jmjd3 is localized both into the cytoplasm and the nucleus, and its nuclear export is dependent on exportin-1
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
at the blastula stage, Jmjd3, Utx and H3K27 methylase Ezh2 show similar expression patterns in the animal cap and marginal zone that give rise to the ectoderm and mesoderm, respectively. The three genes maintain similar expresxadsion patterns in the neural plate, preplacodal ectoderm and axial mesoderm during the gastrula and neurula stages. Later, expression is maintained in the developing brain and cranial sensory tissues, such as the eye and ear, of tailbud embryos
physiological function
both demthylase Utx and Jmjd3 redundantly promote H3K27Me3 removal at, and expression of, a specific subset of genes involved in terminal thymocyte differentiation, especially S1pr1, encoding a sphingosine-phosphate receptor required for thymocyte egress. Thymocyte expression of S1pr1 is not rescued in Jmjd3- and Utx-deficient male mice, which carry the catalytically inactive Utx homolog Uty
physiological function
demethylase UTX mediates removal of H3K27me3 at the Myog and CKm genes. Transactivator Six4 initially recruits UTX to the regulatory region of muscle genes. The resulting loss of H3K27me3 marks is limited to the region upstream of the transcriptional start site. Blocking polymerase Pol II elongation on transcribed genes leads to increased H3K27me3 within the coding region, and formation of bivalent (H3K27me3/H3K4me3) chromatin domains
physiological function
during the monolayer differentiation of mouse embryonic stem cells into neural stem cells, Jmjd3 controls the expression of key regulators and markers of neurogenesis and is required for commitment to the neural lineage. Jmjd3 targets show distinct patterns of H3K27 methylation and expression
physiological function
histone demethylase JMJD3 regulates the expression of neutrophil membrane proteinase 3 (mPR3, EC 3.4.21.76) in lipopolysaccharide-stimulated neutrophils, mostly during the early inflammatory response in sepsis. JMJD3 regulates the expression of mPR3 by changing the level of H3K27me3 in LPS-stimulated neutrophils
physiological function
histone H3 lysine-27 demethylation crucially regulatesT helper cell Th17 differentiation. Activation of naive CD41 T cells immediately induces high expression of Jmjd3. Genetic depletion of Jmjd3 in CD41 T cells specifically impairs Th17 cell differentiation both in vitro and in vivo. Jmjd3-deficient mice are resistant to the induction of experimental autoimmune encephalomyelitis. Inhibition of the H3K27 demethylase activity with the specific inhibitor GSK-J4 dramatically suppresses Th17 cell differentiation in vitro. Jmjd3 directly binds to and reduces the level of H3K27 trimethylation (me3) at the genomic sites of Rorc
physiological function
histone H3K27 demethylase JMJD3 regulates the fragmentation of spermatogonial cysts. Down-regulation of Jmjd3 in spermatogonial stem cells promotes an increase in undifferentiated spermatogonia but does not affect their differentiation. Germ cell-specific Jmjd3 null male mice have larger testes and sire offspring for a longer period compared to controls. Jmjd3 deficiency induces frequent fragmentation of spermatogonial cysts by abscission of intercellular bridges
physiological function
inhibition of Utx1 results in misregulation of hox genes and a striking posterior developmental defect, which is partially rescued by wild-type, but not by catalytically inactive, human Utx
physiological function
JmjC-domain-containing proteins UTX and JMJD3 demethylate tri-methylated Lys 27 on histone H3. Ectopic expression of JMJD3 leads to a strong decrease of H3K27me3 levels and causes delocalization of polycomb proteins in vivo. H3K27me3 demethylation regulated by UTX/JMJD3 proteins is essential for proper development
physiological function
JmjC-domain-containing proteins UTX and JMJD3 demethylate tri-methylated Lys 27 on histone H3. H3K27me3 demethylation regulated by UTX/JMJD3 proteins is essential for proper development
physiological function
JMJD3 is associated with demethylase KIAA1718. JMJD3 and KIAA1718 directly bind to and regulate the expression of a plethora of common target genes in both a demethylase activity-dependent and -independent manner. JMJD3 and KIAA1718 collaborate to demethylate trimethylated H3K27 (H3K27me3) on a subset of their target genes. Reduction of either JMJD3 or KIAA1718 diminishes polymerase Pol II traveling along the gene bodies of the affected genes while having no effect on the promoter-proximal Pol II. JMJD3 and KIAA1718 also play a role in localizing elongation factors SPT6 and SPT16 to the target genes
physiological function
Jmjd3 is expressed in macrophages in response to bacterial products and inflammatory cytokines. Jmjd3 binds PcG target genes and regulates their H3K27me3 levels and transcriptional activity, the activation of Jmjd3 requires NF-kappaB
physiological function
Jmjd3 is involved in brown fat development and white fat browning. A significant subset of brown fat-selective genes, but not common fat genes or white fat-selective genes, are demarcated by H3K27me3 in both brown and white preadipocytes. Jmjd3-catalyzed removal of H3K27me3, in part through Rreb1-mediated recruitment, is required for expression of brown fat-selective genes and for development of beige adipocytes both in vitro and in vivo. Gain- and loss-of-function Jmjd3 transgenic mice show age-dependent body weight reduction and cold intolerance, respectively
physiological function
JMJD3 upregulation and NF-kappaB activation occur in the region of the wound edge during keratinocyte wound healing. JMJD3 interacts with NF-kappaB, resulting in increased expression of the inflammatory matrix metalloproteinase, and growth factor genes via demethylation of H3K27me3 at the gene promoters. Inactivation of JMJD3 or NF-kappaB results in aberrant keratinocyte wound healing
physiological function
loss of Jmjd3 activity causes perinatal lethality with the complete and selective disruption of the pre-Boetzinger complex, the pacemaker of the respiratory rhythm generator. Jmjd3-null mice die at birth of respiratory failure. The enzymatic activity of Jmjd3 is selectively required for the maintenance of the pre-Boetzinger complex and controls critical regulators of pre-Boetzinger complex activity
physiological function
male embryos lacking both H3K27 demethylases Jmjd3 and Utx survive to term. At mid-gestation, embryos demonstrate proper patterning and activation of Hox genes. The embryos retain the Y-chromosome UTtx homolog, UtyY, which cannot demethylate H3K27me3. Embryonic stem cells lacking both Jmjd3 and Utx exhibit a typical decrease in global H3K27me3 levels with differentiation. Retinoic acid differentiations of these embryonic stem cells demonstrate loss of H3K27me3 and gain of H3K4me3 to Hox promoters and other transcription factors, and induce expression similar to control cells. A small subset of genes exhibit decreased expression associated with reduction of promoter H3K4me3 and some low-level accumulation of H3K27me3. Utx and Jmjd3 mutant mouse embryonic fibroblasts demonstrate dramatic loss of H3K27me3 from promoters of several Hox genes and transcription factors
physiological function
microRNA miR-142-3p binds directly to lysine demethylase 6A (KDM6A), which results in demethylation of H3K27me3 and in turn upregulated expression of the anti-apoptotic protein Bcl-2. miR-142-3p knockdown increases autophagy-related protein 16-1-mediated autophagy in in vitro induced human regulatory T cells
physiological function
mutation of JMJD3 orthologue, or inhibition of its expression, results in abnormal gonad development
physiological function
RNAi inhibition of UTX leads to increased H3K27me3 levels at some HOX gene promoters
physiological function
the apoptosis rate of cardiomyocytes is significantly exacerbated when Kdm6a is knocked down. The expression of the Na+/Ca2+ exchanger Ncx is significantly upregulated in cardiomyocytes under hypoxia. Knockdown of Kdm6a downregulates the Ncx expression via enhancing H3K27me3 modification on Ncx gene promoter, and attenuates the intracellular calcium-influx ability in cardiomyocytes as a consequence
physiological function
transfection of JMJD3 into HeLa cells causes a specific reduction of trimethyl H3K27, but has no effect on di- and monomethyl H3K27, or histone lysine methylations on H3K4 and H3K9. The enzymatic activity requires the JmjC domain. JMJD3 directly catalyzes the demethylation
physiological function
UTX occupies the promoters of HOX gene clusters and regulates their transcriptional output by modulating the recruitment of polycomb repressive complex 1 and the monoubiquitination of histone H2A. UTX associates with mixed-lineage leukemia 2/3 complexes, and during retinoic acid signaling events, the recruitment of the UTX complex to HOX genes results in H3K27 demethylation and a concomitant methylation of H3K4
physiological function
UTX specifically removes methyl marks on H3K27 in vitro. The demethylase activity of UTX requires a catalytically active JmjC domain. Overexpression of UTX leads to reduced di- and trimethylation on H3K27 in cells
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). JMJ30_ARATH
429
0
48075
Swiss-Prot
other Location (Reliability: 3)
JMJ32_ARATH
345
0
39123
Swiss-Prot
other Location (Reliability: 2)
JM705_ORYSJ
1286
0
142049
Swiss-Prot
other Location (Reliability: 5)
KDM6A_HUMAN
1401
0
154177
Swiss-Prot
Secretory Pathway (Reliability: 5)
KDM6A_MOUSE
1401
0
154355
Swiss-Prot
Secretory Pathway (Reliability: 3)
KDM6B_HUMAN
1643
0
176632
Swiss-Prot
Mitochondrion (Reliability: 5)
KDM6B_MOUSE
1641
0
176355
Swiss-Prot
Mitochondrion (Reliability: 5)
UTY_HUMAN
1347
1
149548
Swiss-Prot
other Location (Reliability: 3)
UTY_MOUSE
1212
0
136737
Swiss-Prot
other Location (Reliability: 1)
UTY_PANTR
1079
1
118032
Swiss-Prot
other Location (Reliability: 2)
A0A812E8H1_SEPPH
1641
9
185730
TrEMBL
other Location (Reliability: 2)
A0A7R8D4Q1_LEPSM
259
0
29723
TrEMBL
other Location (Reliability: 2)
A0A6J8AMD0_MYTCO
1228
0
138418
TrEMBL
Secretory Pathway (Reliability: 4)
A0A7R8D579_LEPSM
108
0
12514
TrEMBL
other Location (Reliability: 3)
A0A6J8AQW2_MYTCO
1297
0
145932
TrEMBL
Secretory Pathway (Reliability: 4)
A0A6J8AQZ1_MYTCO
1274
0
143428
TrEMBL
Secretory Pathway (Reliability: 4)
A0A7R8D4P8_LEPSM
1183
0
132724
TrEMBL
other Location (Reliability: 2)
A0A812EA49_SEPPH
1640
9
185601
TrEMBL
other Location (Reliability: 2)
K9K8P2_XENTR
1739
0
193362
TrEMBL
other Location (Reliability: 1)
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structures of the catalytic fragment of UTX/KDM6A, in the free and H3 peptide-bound forms. The catalytic jumonji domain binds H3 residues 25-33, recognizing H3R26, H3A29, and H3P30 in a sequence-specific manner, in addition to H3K27me3 in the catalytic pocket. A zinc-binding domain, conserved within the KDM6 family, binds residues 17-21 of H3. The zinc-binding domain changes its conformation upon H3 binding, and thereby recognizes the H3L20 side chain via a hydrophobic patch on its surface, which is inaccessible in the H3-free form. Residues H3R17, H3L20, H3R26, H3A29, H3P30, and H3T32 are each important for demethylation
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E1148A
mutation in the catalytic JmjC-domain of UTX, abrogates enzymatic activity
H1146A
mutation in the catalytic JmjC-domain of UTX, abrogates enzymatic activity
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
GSK-J4 reduces both the mRNA and protein levels of mPR3 significantly compared to controls
JMJD3 is upregulated in prostate cancer, and its expression is higher in metastatic prostate cancer
lipopolysaccharide (LPS) induces JMJD3 expression in vitro. Neutrophil JMJD3 expression is increased in patients with sepsis compared to controls
presence of nickel chloride upregulates the expression of H3K27me3 demethylase Jmjd3 in kidney cancer cells, which is accompanied by the reduction in the protein level of H3K27me3
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
demethylase Kdm6a expression is significantly upregulated in a rat acute myocardial infarction model and in hypoxia induction
medicine
-
H3K27 methylation imposes ligand-dependent regulation of the estrogen receptor alpha-dependent apoptotic response via Bcl-2 in breast cancer cells. The activation of BCL2 transcription is dependent on the simultaneous inactivation of the H3K27 methyltransferase, EZH2, and the demethylation of H3K27 at a poised enhancer by the estrogen receptor alpha-dependent recruitment of JMJD3 in hormone-dependent breast cancer cells. This pathway is modified in cells resistant to anti-estrogen, which constitutively express BCL2
medicine
in renal cell carcinoma, UTX and JMJD3 transcripts are significantly increased compared to normal tissues. The level of trimethylated H3K27 is lower in cancer tissues compared to normal tissues, but expression of the H3K27 methyltransferase EZH2 is increased
medicine
inhibition of JMJD3 and UTX blocks reactivation-induced H3K27me3 demethylation of herpes simplex virus genomes
medicine
JMJD3 is upregulated in prostate cancer, and its expression is higher in metastatic prostate cancer
medicine
JMJD3 upregulation and NF-kappaB activation occur in the region of the wound edge during keratinocyte wound healing. JMJD3 interacts with NF-kappaB, resulting in increased expression of the inflammatory matrix metalloproteinase, and growth factor genes via demethylation of H3K27me3 at the gene promoters. Inactivation of JMJD3 or NF-kappaB results in aberrant keratinocyte wound healing
medicine
presence of nickel chloride upregulates the expression of H3K27me3 demethylase Jmjd3 in kidney cancer cells, which is accompanied by the reduction in the protein level of H3K27me3
medicine
upon exposure of macrophages to Bacillus anthracis, lethal toxin, substantial cell death is induced with a survival rate of around 40%. The expression of Jmjd3 is induced 8fold in intoxication-resistant cells generated by treatment with lipopolysaccharides of RAW 264.7 cells. These intoxication-resistant cell lines are maintained for 8 passages and have a survival rate of around 100% on secondary exposure to lethal toxin and lipopolysaccharides
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Na, J.; Lee, K.; Na, W.; Shin, J.; Lee, M.; Yune, T.; Lee, H.; Jung, H.; Kim, W.; Ju, B.
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Homo sapiens (O15054)
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brenda
Shen, Y.; Guo, X.; Wang, Y.; Qiu, W.; Chang, Y.; Zhang, A.; Duan, X.
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Homo sapiens (O15054), Homo sapiens (O15550)
brenda
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The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing
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Mus musculus (Q5NCY0)
brenda
Gao, J.; Gu, J.; Pan, X.; Gan, X.; Ju, Z.; Zhang, S.; Xia, Y.; Lu, L.; Wang, X.
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Homo sapiens (O15550), Homo sapiens
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Mus musculus (Q5NCY0)
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Homo sapiens (O15054)
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Mus musculus (Q5NCY0)
brenda
Seenundun, S.; Rampalli, S.; Liu, Q.C.; Aziz, A.; Palii, C.; Hong, S.; Blais, A.; Brand, M.; Ge, K.; Dilworth, F.J.
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Mus musculus (O70546)
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Homo sapiens
brenda
Kamikawa, Y.F.; Donohoe, M.E.
The localization of histone H3K27me3 demethylase Jmjd3 is dynamically regulated
Epigenetics
9
834-841
2014
Homo sapiens (O15054), Mus musculus (Q5NCY0)
brenda
Sengoku, T.; Yokoyama, S.
Structural basis for histone H3 Lys 27 demethylation by UTX/KDM6A
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2011
Homo sapiens (O15550)
brenda
Chen, S.; Ma, J.; Wu, F.; Xiong, L.J.; Ma, H.; Xu, W.; Lv, R.; Li, X.; Villen, J.; Gygi, S.P.; Liu, X.S.; Shi, Y.
The histone H3 Lys 27 demethylase JMJD3 regulates gene expression by impacting transcriptional elongation
Genes Dev.
26
1364-1375
2012
Homo sapiens (O15054)
brenda
Chen, Y.; Liu, Z.; Pan, T.; Chen, E.; Mao, E.; Chen, Y.; Tan, R.; Wang, X.; Tian, R.; Liu, J.; Qu, H.
JMJD3 is involved in neutrophil membrane proteinase 3 overexpression during the hyperinflammatory response in early sepsis
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59
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Homo sapiens (O15054)
brenda
Kawaguchi, A.; Ochi, H.; Sudou, N.; Ogino, H.
Comparative expression analysis of the H3K27 demethylases, JMJD3 and UTX, with the H3K27 methylase, EZH2, in Xenopus
Int. J. Dev. Biol.
56
295-300
2012
Xenopus tropicalis (K9K8P2)
brenda
Li, Y.; Quan, X.; Li, X.; Pan, Y.; Zhang, T.; Liang, Z.; Wang, Y.
Kdm6A protects against hypoxia-induced cardiomyocyte apoptosis via H3K27me3 demethylation of Ncx gene
J. Cardiovasc. Transl. Res.
12
488-495
2019
Rattus norvegicus (A0A0G2K6D0)
brenda
Liu, Z.; Cao, W.; Xu, L.; Chen, X.; Zhan, Y.; Yang, Q.; Liu, S.; Chen, P.; Jiang, Y.; Sun, X.; Tao, Y.; Hu, Y.; Li, C.; Wang, Q.; Wang, Y.; Chen, C.D.; Shi, Y.; Zhang, X.
The histone H3 lysine-27 demethylase Jmjd3 plays a critical role in specific regulation of Th17 cell differentiation
J. Mol. Cell Biol.
7
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2015
Mus musculus (Q5NCY0)
brenda
Messer, H.G.; Jacobs, D.; Dhummakupt, A.; Bloom, D.C.
Inhibition of H3K27me3-specific histone demethylases JMJD3 and UTX blocks reactivation of herpes simplex virus 1 in trigeminal ganglion neurons
J. Virol.
89
3417-3420
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Mus musculus (O70546), Mus musculus (Q5NCY0)
brenda
Manna, S.; Kim, J.; Bauge, C.; Cam, M.; Zhao, Y.; Shetty, J.; Vacchio, M.; Castro, E.; Tran, B.; Tessarollo, L.; Bosselut, R.
Histone H3 lysine 27 demethylases Jmjd3 and Utx are required for T-cell differentiation
Nat. Commun.
6
8152
2015
Mus musculus (Q5NCY0)
brenda
Lan, F.; Bayliss, P.E.; Rinn, J.L.; Whetstine, J.R.; Wang, J.K.; Chen, S.; Iwase, S.; Alpatov, R.; Issaeva, I.; Canaani, E.; Roberts, T.M.; Chang, H.Y.; Shi, Y.
A histone H3 lysine 27 demethylase regulates animal posterior development
Nature
449
689-694
2007
Danio rerio (A1L1S9), Homo sapiens (O15550)
brenda
Agger, K.; Cloos, P.A.; Christensen, J.; Pasini, D.; Rose, S.; Rappsilber, J.; Issaeva, I.; Canaani, E.; Salcini, A.E.; Helin, K.
UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development
Nature
449
731-734
2007
Homo sapiens (O15054), Homo sapiens (O15550), Homo sapiens, Caenorhabditis elegans (Q95QK3), Caenorhabditis elegans
brenda
Shpargel, K.B.; Starmer, J.; Yee, D.; Pohlers, M.; Magnuson, T.
KDM6 demethylase independent loss of histone H3 lysine 27 trimethylation during early embryonic development
PLoS Genet.
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2014
Mus musculus (O70546), Mus musculus (Q5NCY0)
brenda
Burgold, T.; Spreafico, F.; De Santa, F.; Totaro, M.; Prosperini, E.; Natoli, G.; Testa, G.
The histone H3 lysine 27-specific demethylase Jmjd3 is required for neural commitment
PLoS ONE
3
e3404
2008
Mus musculus (Q5NCY0)
brenda
Das, N.; Jung, K.; Chai, Y.
The role of NF-kappaB and H3K27me3 demethylase, Jmjd3, on the anthrax lethal toxin tolerance of RAW 264.7 cells
PLoS ONE
5
e9913
2010
Mus musculus (Q5NCY0)
brenda
Iwamori, N.; Iwamori, T.; Matzuk, M.M.
H3K27 demethylase, JMJD3, regulates fragmentation of spermatogonial cysts
PLoS One
8
e72689
2013
Mus musculus (Q5NCY0)
brenda
Hong, S.; Cho, Y.W.; Yu, L.R.; Yu, H.; Veenstra, T.D.; Ge, K.
Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases
Proc. Natl. Acad. Sci. USA
104
18439-18444
2007
Homo sapiens (O15550)
brenda
Lee, M.G.; Villa, R.; Trojer, P.; Norman, J.; Yan, K.P.; Reinberg, D.; Di Croce, L.; Shiekhattar, R.
Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination
Science
318
447-450
2007
Homo sapiens (O15550)
brenda
Guo, X.; Zhang, Y.; Zhang, Q.; Fa, P.; Gui, Y.; Gao, G.; Cai, Z.
The regulatory role of nickel on H3K27 demethylase JMJD3 in kidney cancer cells
Toxicol. Ind. Health
32
1286-92
2016
Homo sapiens (O15054)
brenda
Romani, M.; Daga, A.; Forlani, A.; Pistillo, M.P.; Banelli, B.
Targeting of histone demethylases KDM5A and KDM6B inhibits the proliferation of temozolomide-resistant glioblastoma cells
Cancers (Basel)
11
878
2019
Homo sapiens (O15054)
brenda
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