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Literature summary extracted from

  • Lloret-Llinares, M.; Carre, C.; Vaquero, A.; de Olano, N.; Azorin, F.
    Characterization of Drosophila melanogaster JmjC+N histone demethylases (2008), Nucleic Acids Res., 36, 2852-2863 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.14.11.66 gene CG15835 or Kdm4A, sequence comparisons, recombinant overexpression of FLAG-tagged wild-type and mutant enzymes in S2 cells Drosophila melanogaster
1.14.11.66 gene CG33182, sequence comparisons, recombinant overexpression of FLAG-tagged enzyme in S2 cells Drosophila melanogaster
1.14.11.67 gene CG3654, sequence comparisons, recombinant overexpression of FLAG-tagged enzyme in S2 cells. Overexpression experiments, performed both in S2 cells and flies, fail to detect any demethylase activity of dJARID2/CG3654 on H3K4me3, H3K9me3, H3K27me3, H3K36me3 and H4K20me3 Drosophila melanogaster
1.14.11.69 gene CG15835 or Kdm4A, sequence comparisons, recombinant overexpression of FLAG-tagged wild-type and mutant enzymes in S2 cells Drosophila melanogaster
1.14.11.69 gene CG33182, sequence comparisons, recombinant overexpression of FLAG-tagged enzyme in S2 cells Drosophila melanogaster
1.14.99.66 gene lid, sequence comparisons, transient recombinant overexpression of FLAG-tagged enzyme in S2 cells Drosophila melanogaster

Protein Variants

EC Number Protein Variants Comment Organism
1.14.11.66 H195A site-directed mutagenesis, mutation of an Fe2+ binding residue, abolishes demethylase activity of dJMJD2(1)/CG15835 Drosophila melanogaster
1.14.11.66 additional information construction of transgenic lines carrying a UASGAL4-CG15835-Flag construct, where expression of dJMJD2(1)/CG15835 is under the control of the yeast activator GAL4, allowing its overexpression upon crossing with lines expressing GAL4. Overexpression of CG15835 results in spreading of HP1 into euchromatin and a strong decrease on the levels of H3K9me3 and H3K36me3 Drosophila melanogaster
1.14.11.67 additional information GH09982 (CG3654) corresponds to a truncated form missing part of the N-terminal region but carrying the complete C-terminal part containing the JmjN, JmjC and ARID domains (amino acid positions 1521 to 2351). Overexpression of CG3654 shows no significant effect on the levels of H3K4me3, H3K9me3, H3K27me3, H3K36me3 and H4K20me3 Drosophila melanogaster
1.14.11.69 H195A site-directed mutagenesis, mutation of an Fe2+ binding residue, abolishes demethylase activity of dJMJD2(1)/CG15835 Drosophila melanogaster
1.14.11.69 additional information construction of transgenic lines carrying a UASGAL4-CG15835-Flag construct, where expression of dJMJD2(1)/CG15835 is under the control of the yeast activator GAL4, allowing its overexpression upon crossing with lines expressing GAL4. Overexpression of CG15835 results in spreading of HP1 into euchromatin and a strong decrease on the levels of H3K9me3 and H3K36me3 Drosophila melanogaster
1.14.99.66 additional information overexpression of dJARID1/Lid results in a strong reduction in the overall levels of H3K4me3. A strong increase in H3K4me3 is also detected in polytene chromosomes from homozygous lid12367 mutants. Gene lid mutations resulting in small imaginal discs. In homozygous lid12367 larvae, the pattern of Ubx expression is not altered but expression in haltere discs is reduced being similar to that observed in leg discs, which is in contrast with the much higher expression in haltere versus leg discs observed in wild-type larvae Drosophila melanogaster

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.14.11.66 nucleus
-
 Drosophila melanogaster 5634
-
1.14.99.66 nucleus
-
 Drosophila melanogaster 5634
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.14.11.66 Fe2+ required for catalytic activity Drosophila melanogaster
1.14.11.66 Fe2+ required for catalytic activity. The coordination of Fe(II) involves residues H195, E197 and H223 Drosophila melanogaster
1.14.11.69 Fe2+ required for catalytic activity Drosophila melanogaster
1.14.11.69 Fe2+ required for catalytic activity. The coordination of Fe(II) involves residues H195, E197 and H223 Drosophila melanogaster

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.14.11.66 [histone H3]-N6,N6,N6-trimethyl-L-lysine 9 + 2-oxoglutarate + O2 Drosophila melanogaster
-
 [histone H3]-N6,N6-dimethyl-L-lysine 9 + succinate + formaldehyde + CO2
-
 ?
1.14.11.66 [histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2 Drosophila melanogaster
-
 [histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
 ?
1.14.11.69 [histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2 Drosophila melanogaster
-
 [histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
 ?
1.14.11.69 [histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2 Drosophila melanogaster
-
 [histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
-
 ?
1.14.99.66 [histone H3]-N6,N6-dimethyl-L-lysine4 + 2 acceptor + 2 H2O Drosophila melanogaster overall reaction [histone H3]-L-lysine4 + 2 formaldehyde + 2 reduced acceptor
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.14.11.66 Drosophila melanogaster Q9V333
-
-
1.14.11.66 Drosophila melanogaster Q9V6L0
-
-
1.14.11.67 Drosophila melanogaster Q9VT00
-
-
1.14.11.69 Drosophila melanogaster Q9V333
-
-
1.14.11.69 Drosophila melanogaster Q9V6L0
-
-
1.14.99.66 Drosophila melanogaster Q9VMJ7
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.14.11.66 larva
-
 Drosophila melanogaster
-
1.14.11.66 salivary gland
-
 Drosophila melanogaster
-
1.14.11.67 larva
-
 Drosophila melanogaster
-
1.14.11.67 salivary gland
-
 Drosophila melanogaster
-
1.14.11.69 larva
-
 Drosophila melanogaster
-
1.14.11.69 salivary gland
-
 Drosophila melanogaster
-
1.14.99.66 larva
-
 Drosophila melanogaster
-
1.14.99.66 salivary gland
-
 Drosophila melanogaster
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.14.11.66 additional information dJMJD2(1)/CG15835 is capable of demethylating H3K9me3 and H3K36me3 Drosophila melanogaster ?
-
 ?
1.14.11.66 additional information dJMJD2(2)/CG33182 is capable of demethylating H3K9me3 and H3K36me3 Drosophila melanogaster ?
-
 ?
1.14.11.66 [histone H3]-N6,N6,N6-trimethyl-L-lysine 9 + 2-oxoglutarate + O2
-
 Drosophila melanogaster [histone H3]-N6,N6-dimethyl-L-lysine 9 + succinate + formaldehyde + CO2
-
 ?
1.14.11.66 [histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2
-
 Drosophila melanogaster [histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2
-
 ?
1.14.11.69 additional information dJMJD2(1)/CG15835 is capable of demethylating H3K9me3 and H3K36me3 Drosophila melanogaster ?
-
 ?
1.14.11.69 additional information dJMJD2(2)/CG33182 is capable of demethylating H3K9me3 and H3K36me3 Drosophila melanogaster ?
-
 ?
1.14.11.69 [histone H3]-N6,N6,N6-trimethyl-L-lysine 36 + 2-oxoglutarate + O2
-
 Drosophila melanogaster [histone H3]-N6,N6-dimethyl-L-lysine 36 + succinate + formaldehyde + CO2
-
 ?
1.14.11.69 [histone H3]-N6,N6-dimethyl-L-lysine 36 + 2-oxoglutarate + O2
-
 Drosophila melanogaster [histone H3]-N6-methyl-L-lysine 36 + succinate + formaldehyde + CO2
-
 ?
1.14.99.66 [histone H3]-N6,N6-dimethyl-L-lysine4 + 2 acceptor + 2 H2O overall reaction Drosophila melanogaster [histone H3]-L-lysine4 + 2 formaldehyde + 2 reduced acceptor
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.14.11.66 CG15835
-
 Drosophila melanogaster
1.14.11.66 CG33182
-
 Drosophila melanogaster
1.14.11.66 KDM4A
-
 Drosophila melanogaster
1.14.11.66 KDM4B
-
 Drosophila melanogaster
1.14.11.66 LD33386
-
 Drosophila melanogaster
1.14.11.66 More see also EC 1.14.11.69 Drosophila melanogaster
1.14.11.67 CG3654
-
 Drosophila melanogaster
1.14.11.67 dJARID2
-
 Drosophila melanogaster
1.14.11.67 dJARID2/CG3654
-
 Drosophila melanogaster
1.14.11.67 GH09982
-
 Drosophila melanogaster
1.14.11.67 Jarid2
-
 Drosophila melanogaster
1.14.11.69 CG15835
-
 Drosophila melanogaster
1.14.11.69 CG33182
-
 Drosophila melanogaster
1.14.11.69 KDM4A
-
 Drosophila melanogaster
1.14.11.69 KDM4B
-
 Drosophila melanogaster
1.14.11.69 LD33386
-
 Drosophila melanogaster
1.14.11.69 More see also EC 1.14.11.66 Drosophila melanogaster
1.14.99.66 dJARID1/Lid
-
 Drosophila melanogaster
1.14.99.66 Jarid1
-
 Drosophila melanogaster
1.14.99.66 LD40310
-
 Drosophila melanogaster
1.14.99.66 Lid
-
 Drosophila melanogaster

General Information

EC Number General Information Comment Organism
1.14.11.66 evolution enzyme CG15835 shows higher identity to mammalian JMJD2D (40%) than to any of the other mammalian JMJD2 isoforms (22%) Drosophila melanogaster
1.14.11.66 evolution enzyme CG33182 shows higher identity to mammalian JMJD2D (40%) than to any of the other mammalian JMJD2 isoforms (22%) Drosophila melanogaster
1.14.11.66 malfunction overexpression of CG15835 results in spreading of HP1 into euchromatin and a strong decrease on the levels of H3K9me3 and H3K36me3, while the levels of H3K4me3 and H3K27me3 are not significantly altered. Demethylase activity of dJMJD2(1)/CG15835 depends on the JmjC domain, as it is abolished by mutations that affect its catalytic activity. The single-point mutation H195A, mutating one of the Fe2+ binding residues, abolishes demethylase activity of dJMJD2(1)/CG15835 Drosophila melanogaster
1.14.11.66 physiological function HP1 is known to recognize H3K9me3/me2, a modification that is specifically enriched at heterochromatin Drosophila melanogaster
1.14.11.66 physiological function specific recognition of H3K9me3/me2 is known to regulate binding of HP1 to chromatin. dJMJD2(1)/CG15835 influences heterochromatin organization, but is excluded from heterochromatin. Overexpression of dJMJD2(1)/CG15835 does not affect the pattern of H3K9me3/me2 at heterochromatin. dJMJD2(1)/CG15835 localizes to multiple euchromatic sites, where it mostly regulates H3K36me3, as its overexpression results in a strong decrease in the levels of H3K36me3. dJMJD2(1)/CG15835 regulates spreading of HP1 Drosophila melanogaster
1.14.11.67 evolution the enzyme belongs to the JARID family. JARID proteins contain, in addition to the JmjN and JmjC domains, ARID and C5HC2-zinc finger domains, which mediate DNA binding. JARID proteins are, in turn, divided into two subgroups according to the presence, JARID1, or not, JARID2, of chromatin-binding PHD domains. CG3654 is the structural homologue of mammalian JARID2, as it does not contain any chromatin-binding domains. In this case, however, identity is lower (15%) and, in addition, CG3654 is missing the C5HC2-zinc finger domain present in mammalian JARID2 Drosophila melanogaster
1.14.11.67 additional information overexpression of CG3654 shows no significant effect on the levels of H3K4me3, H3K9me3, H3K27me3, H3K36me3 and H4K20me3 Drosophila melanogaster
1.14.11.67 physiological function methylation of H3K4 prevents spreading of heterochromatin. Both H3K36 and H3K4 methylation associate to actively transcribed genes, suggesting that gene activity is a main determinant to delimit hetero- and euchromatic territories. H3K4me3 is an epigenetic mark that correlates with transcriptionally active genes Drosophila melanogaster
1.14.11.69 evolution enzyme CG15835 shows higher identity to mammalian JMJD2D (40%) than to any of the other mammalian JMJD2 isoforms (22%) Drosophila melanogaster
1.14.11.69 evolution enzyme CG33182 shows higher identity to mammalian JMJD2D (40%) than to any of the other mammalian JMJD2 isoforms (22%) Drosophila melanogaster
1.14.11.69 malfunction overexpression of CG15835 results in spreading of HP1 into euchromatin and a strong decrease on the levels of H3K9me3 and H3K36me3, while the levels of H3K4me3 and H3K27me3 are not significantly altered. Demethylase activity of dJMJD2(1)/CG15835 depends on the JmjC domain, as it is abolished by mutations that affect its catalytic activity. The single-point mutation H195A, mutating one of the Fe2+ binding residues, abolishes demethylase activity of dJMJD2(1)/CG15835 Drosophila melanogaster
1.14.11.69 physiological function H3K36me3 acts as a barrier that prevents spreading of HP1 into euchromatin. Both H3K36 and H3K4 methylation associate to actively transcribed genes, suggesting that gene activity is a main determinant to delimit hetero- and euchromatic territories Drosophila melanogaster
1.14.11.69 physiological function H3K36me3 acts as a barrier that prevents spreading of HP1 into euchromatin. Both H3K36 and H3K4 methylation associate to actively transcribed genes, suggesting that gene activity is a main determinant to delimit hetero- and euchromatic territories. dJMJD2(1)/CG15835 influences heterochromatin organization, but is excluded from heterochromatin. Overexpression of dJMJD2(1)/CG15835 does not affect the pattern of H3K9me2,3 at heterochromatin. dJMJD2(1)/CG15835 localizes to multiple euchromatic sites, where it mostly regulates H3K36me3, as its overexpression results in a strong decrease in the levels of H3K36me3. dJMJD2(1)/CG15835 regulates spreading of HP1 Drosophila melanogaster
1.14.99.66 evolution the enzyme belongs to the JARID family. JARID proteins contain, in addition to the JmjN and JmjC domains, ARID and C5HC2-zinc finger domains, which mediate DNA binding. JARID proteins are, in turn, divided into two subgroups according to the presence, JARID1, or not, JARID2, of chromatin-binding PHD domains Drosophila melanogaster
1.14.99.66 malfunction a strong increase in H3K4me3 is detected in polytene chromosomes from homozygous lid12367 mutants. Gene lid mutations result in small imaginal discs Drosophila melanogaster
1.14.99.66 physiological function overexpression of dJARID1/Lid results in a strong reduction in the overall levels of H3K4me3, on the other hand, no significant effects on the levels of H3K9me3, H3K27me3 and H3K36me3 are detected. Independent of its demethylase activity, lid regulates cell proliferation through its interaction with myc Drosophila melanogaster