Literature summary for 1.14.11.67 extracted from

Horton, J.R.; Engstrom, A.; Zoeller, E.L.; Liu, X.; Shanks, J.R.; Zhang, X.; Johns, M.A.; Vertino, P.M.; Fu, H.; Cheng, X.
Characterization of a linked Jumonji domain of the KDM5/JARID1 family of histone H3 lysine 4 demethylases (2016), J. Biol. Chem., 291, 2631-2646 .

Search for more literature for 1.14.11.67

Cloned(Commentary)

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

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

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 [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

Metals/Ions	Comment	Organism	Structure
Fe2+	required for catalysis	Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism	UniProt	Comment	Textmining
Homo sapiens	P29375	-	-
Homo sapiens	P41229	-	-
Homo sapiens	Q9UGL1	-	-

Purification (Commentary)

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 and Products (Substrate)

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

Subunits	Comment	Organism
More	KDM5 domain structure and functional analysis, overview	Homo sapiens

Synonyms

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

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

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Release 2023.1 (January 2023)