Cloned (Comment) | Organism |
---|---|
gene KDM5A, recombinant expression of soluble His-SUMO-tagged enzyme in Escherichia coli strain BL21(DE3)C+ | Homo sapiens |
gene KDM5B, recombinant expression of soluble His-SUMO-tagged enzyme in Escherichia coli strain BL21(DE3)C+ | Homo sapiens |
gene KDM5C, recombinant expression ofsoluble His-SUMO-tagged enzyme in Escherichia coli strain BL21(DE3)C+ | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | internal deletion of the ARID and PHD1 domains has a negligible effect on in vitro enzymatic kinetics of the KDM5 family of enzymes | Homo sapiens |
additional information | internal deletion of the ARID and PHD1 domains has a negligible effect on in vitro enzymatic kinetics of the KDM5 family of enzymes. Generation of a KDM5B(1-755)DELTAAP mutant by deleting ARID and PHD1 (AP) domains by connecting residues 100 and 363. The DELTAAP constructs represent the domain arrangement of the conventional Jumonji domain followed by a C-terminal helical zinc binding domain. Deletion of DELTAAP has no effect on kinetics of KDM5C | Homo sapiens |
additional information | internal deletion of the ARID and PHD1 domains has a negligible effect on in vitro enzymatic kinetics of the KDM5 family of enzymes. Generation of a KDM5C(1-789)DELTAAP mutant by deleting ARID and PHD1 (AP) domains by connecting residues 100 and 363. The DELTAAP constructs represent the domain arrangement of the conventional Jumonji domain followed by a C-terminal helical zinc binding domain | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
GSK-J1 | a selective inhibitor of the KDM6/KDM5 subfamilies. Docking study and identification of critical residues for binding of the inhibitor to the reconstituted KDM5 Jumonji domain; a selective inhibitor of the KDM6/KDM5 subfamilies. Docking study and identification of critical residues for binding of the inhibitor to the reconstituted KDM5 Jumonji domain. GSK-J1 inhibits the demethylase activity of KDM5C with 8.5fold increased potency compared with that of KDM5B at 1 mM 2-oxoglutarate. Also inhibits the enzyme mutant KDM5BDELTAAP; a selective inhibitor of the KDM6/KDM5 subfamilies. Docking study and identification of critical residues for binding of the inhibitor to the reconstituted KDM5 Jumonji domain. GSK-J1 inhibits the demethylase activity of KDM5C with 8.5fold increased potency compared with that of KDM5B at 1 mM 2-oxoglutarate. Also inhibits the enzyme mutant KDM5CDELTAAP | Homo sapiens | |
JIB-04 | a pan-inhibitor of the Jumonji demethylase superfamily; a pan-inhibitor of the Jumonji demethylase superfamily, that is about 8fold more potent against KDM5B than against KDM5C. Also inhibits the enzyme mutant KDM5BDELTAAP; a pan-inhibitor of the Jumonji demethylase superfamily, that is about 8fold more potent against KDM5B than against KDM5C. Also inhibits the enzyme mutant KDM5CDELTAAP | Homo sapiens | |
additional information | structural characterization of the linked JmjN-JmjC domain for the KDM5 family for the design of KDM5 demethylase inhibitors with improved potency and selectivity; structural characterization of the linked JmjN-JmjC domain for the KDM5 family for the design of KDM5 demethylase inhibitors with improved potency and selectivity; structural characterization of the linked JmjN-JmjC domain for the KDM5 family for the design of KDM5 demethylase inhibitors with improved potency and selectivity, hypothetical modeling of the N-terminal half of KDM5, overview | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | Michaelis-Menten kinetics of wild-type and mutant enzymes | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Fe2+ | required for catalysis | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
histone H3 N6,N6,N6-trimethyl-L-lysine4 + 2-oxoglutarate + O2 | Homo sapiens | - |
histone H3 N6,N6-dimethyl-L-lysine4 + succinate + formaldehyde + CO2 | - |
? | |
histone H3 N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2 | Homo sapiens | - |
histone H3 N6-methyl-L-lysine4 + succinate + formaldehyde + CO2 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P29375 | - |
- |
Homo sapiens | P41229 | - |
- |
Homo sapiens | Q9UGL1 | - |
- |
Purification (Comment) | Organism |
---|---|
recombinant His-SUMO-tagged enzyme from Escherichia coli strain BL21(DE3)C+ by nickel affinity chromatography, tag cleavage overnight by Ulp-1 protease, followed by anion exchange chromatography, gel filtration, and ultrafiltration | Homo sapiens |
recombinant His-SUMO-tagged enzyme from Escherichia coli strain BL21(DE3)C+ by nickel affinity chromatography, tag cleavage overnight by Ulp-1 protease, followed by anion exchange chromatography, gel filtration, and ultrafiltration. Deletion of DELTAAP has no effect on kinetics of KDM5C | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
histone H3 N6,N6,N6-trimethyl-L-lysine4 + 2-oxoglutarate + O2 | - |
Homo sapiens | histone H3 N6,N6-dimethyl-L-lysine4 + succinate + formaldehyde + CO2 | - |
? | |
histone H3 N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2 | - |
Homo sapiens | histone H3 N6-methyl-L-lysine4 + succinate + formaldehyde + CO2 | - |
? | |
additional information | no activity with monomethylated H3K4 | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | KDM5 domain structure and functional analysis, overview | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
histone H3 lysine 4 demethylase | - |
Homo sapiens |
Jarid1a | - |
Homo sapiens |
JARID1B | - |
Homo sapiens |
JARID1C | - |
Homo sapiens |
KDM5A | - |
Homo sapiens |
KDM5B | - |
Homo sapiens |
KDM5C | - |
Homo sapiens |
PLU1 | - |
Homo sapiens |
RBP2 | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
evolution | the enzyme blongs to the KDM5/JARID1 subfamily of histone H3 lysine 4 demethylases of the Fe(II)- and 2-oxoglutarate-dependent demethylases family. The KDM5 family is unique among the Jumonji domain-containing histone demethylases in that there is an atypical insertion of a DNA-binding ARID domain and a histone-binding PHD domain into the Jumonji domain, which separates the catalytic domain into two fragments (JmjN and JmjC) | Homo sapiens |
malfunction | internal deletion of the ARID and PHD1 domains has a negligible effect on in vitro enzymatic kinetics of the KDM5 family of enzymes | Homo sapiens |
additional information | minimal requirements for enzymatic activity of the KDM5 family is the linked JmjNJmjC domain coupled with the immediate C-terminal helical zinc-binding domain | Homo sapiens |
additional information | minimal requirements for enzymatic activity of the KDM5 family is the linked JmjNJmjC domain coupled with the immediate C-terminal helical zinc-binding domain, hypothetical modeling of the N-terminal half of KDM5, overview | Homo sapiens |
physiological function | role for KDM5A (JARID1A/RBP2) as oncogenic driver | Homo sapiens |
physiological function | role for KDM5B (JARID1B/PLU1) as oncogenic driver | Homo sapiens |