Literature summary for 1.14.11.67 extracted from

Klein, B.J.; Piao, L.; Xi, Y.; Rincon-Arano, H.; Rothbart, S.B.; Peng, D.; Wen, H.; Larson, C.; Zhang, X.; Zheng, X.; Cortazar, M.A.; Pena, P.V.; Mangan, A.; Bentley, D.L.; Strahl, B.D.; Groudine, M.; Li, W.; Shi, X.; Kutateladze, T.G.
The histone-H3K4-specific demethylase KDM5B binds to its substrate and product through distinct PHD fingers (2014), Cell Rep., 6, 325-335 .

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Cloned(Commentary)

Cloned (Comment)	Organism
stable expression of Flag-tagged KDM5B in HEK-293 cells	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
D328A	site-directed mutagenesis, a loss-of-function mutations in the PHD1 finger domain	Homo sapiens
L326W	site-directed mutagenesis, a loss-of-function mutations in the PHD1 finger domain	Homo sapiens
W1502A	site-directed mutagenesis, a loss-of-function mutations in the PHD3 finger domain	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
chromatin	KDM5B colocalizes with HDAC1 and CHD4 at chromatin in K-562 cells	Homo sapiens	785	-
nucleus	-	Homo sapiens	5634	-

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	-	?
histone H3 N6-methyl-L-lysine4 + 2-oxoglutarate + O2	Homo sapiens	-	histone H3 L-lysine4 + succinate + formaldehyde + CO2	-	?
additional information	Homo sapiens	KDM5B associates with the deacetylase NuRD complex	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q9UGL1	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
76NF2V cell	-	Homo sapiens	-
AU-565 cell	low KDM5B expression level	Homo sapiens	-
K-562 cell	-	Homo sapiens	-
MCF-10A cell	-	Homo sapiens	-
MCF-7 cell	high KDM5B expression level	Homo sapiens	-
MDA-MB-231 cell	low KDM5B expression level	Homo sapiens	-
MDA-MB-361 cell	high KDM5B expression level	Homo sapiens	-
MDA-MB-436 cell	low KDM5B expression level	Homo sapiens	-
MDA-MB-468 cell	low KDM5B expression level	Homo sapiens	-
additional information	the expression level of KDM5B is significantly lower in breast cancer estrogen receptor lacking ER- cells compared to ER+ cells, e.g. lower expression levels of KDM5B in the triple-negative breast cancer patients compared with patients with the ER+/PR+ subtype	Homo sapiens	-
SK-BR-3 cell	HER2+SKBR3 cell, low KDM5B expression level	Homo sapiens	-
SKBR-3 cell	low KDM5B expression level	Homo sapiens	-
T-47D cell	high KDM5B expression level	Homo sapiens	-
UACC-812 cell	high KDM5B expression level	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	-	?
histone H3 N6-methyl-L-lysine4 + 2-oxoglutarate + O2	-	Homo sapiens	histone H3 L-lysine4 + succinate + formaldehyde + CO2	-	?
additional information	KDM5B associates with the deacetylase NuRD complex	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
histone lysine demethylase	-	Homo sapiens
histone-H3K4-specific demethylase	-	Homo sapiens
KDM5B	-	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	423 genes are upregulated and 333 genes are downregulated in KDM5B knockdown MDA-MB 231 cells, downregulated genes in KDM5B knockdown cells do not cluster. The expression of the KDM5B-dependent genes is validated by quantitative real-time PCR. The PHD1 finger mutants may act as dominant-negative mutants, altering the dynamics and interactions of endogenous KDM5B. In contrast, the W1502A mutant of PHD3 that is defective in H3K4me3 binding shows an inhibitory effect oncell migration similar to the effect of the wild-type protein	Homo sapiens
metabolism	KDM5B associates with the deacetylase NuRD complex, i.e. with two catalytic subunits of the NuRD complex. One subunit is a chromodomain helicase DNA binding protein 4 (CHD4) ATPase, which hydrolyses ATP necessary for DNA sliding and repositioning of nucleosomes. The second catalytic subunit is histone deacetylase 1 (HDAC1), which deacetylates acetylated lysine residues of histones. KDM5B is recruited to about 140000 genomic regions, and 76268 of these regions overlap with the regions occupied by HDAC1. About 50% of the KDM5B-HDAC1 binding sites overlap with tri-, di-, or monomethylated H3K4 (H3K4me3/2/1), which are substrates for the KDM5B enzymatic activity	Homo sapiens
additional information	enzyme KDM5B contains multiple conserved chromatin-associated domains, including three PHD fingers. The first and third, but not the second, PHD finger of KDM5B possess histone binding activities. The PHD1 finger is highly specific for unmodified histone H3 (H3K4me0), whereas the PHD3 finger shows preference for the trimethylated histone mark H3K4me3, but also binds H3K4me0. Mechanism of H3K4me0 recognition by PHD1, the H3K4me0 binding mode is conserved overview. KDM5B inhibits the migration and invasion abilities of MDA-MB 231 breast cancer cells, and binding of the PHD1 finger to H3K4me0 is required to suppress cell migration	Homo sapiens
physiological function	histone lysine demethylase KDM5B regulates gene transcription and cell differentiation and is implicated in carcinogenesis	Homo sapiens

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Release 2023.1 (January 2023)