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Literature summary extracted from
- Histone demethylase PHF8 regulates hypoxia signaling through HIF1alpha and H3K4me3 (2017), Biochim. Biophys. Acta, 1860, 1002-1012 .
Protein Variants
| EC Number | Protein Variants | Comment | Organism |
|---|---|---|---|
| 1.14.11.65 | F279S | site-directed mutagenesis | Homo sapiens |
| 1.14.11.65 | additional information | knockdown or knockout of PHF8 in 293T cells by RNAi or CRISPR-Cas9 system. The small guide RNAs (sgRNAs) target exon 8, which encodes amino acids 262-315 of the JmjC domain, and abolish PHF8 expression | Homo sapiens |
| 1.14.11.67 | F279S | catalytically lethal mutant | Homo sapiens |
| 1.14.18.B1 | additional information | knockdown or knockout of PHF8 by RNAi or CRISPR-Cas9 system | Homo sapiens |
Localization
| EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|---|
| 1.14.11.65 | nucleus | - |
Homo sapiens | 5634 | - |
| 1.14.18.B1 | nucleus | - |
Homo sapiens | 5634 | - |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.14.11.65 | [histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2 | Homo sapiens | - |
[histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2 | - |
? |  |
| 1.14.11.65 | [histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2 | Homo sapiens | - |
[histone H3]-L-lysine 9 + succinate + formaldehyde + CO2 | - |
? | |
| 1.14.11.67 | [histone H3]-N6,N6,N6-trimethyl-L-lysine4 + 2-oxoglutarate + O2 | Homo sapiens | - |
[histone H3]-N6,N6-dimethyl-L-lysine4 + succinate + formaldehyde + CO2 | - |
? | |
| 1.14.11.67 | [histone H3]-N6,N6,N6-trimethyl-L-lysine4 + 3 2-oxoglutarate + 3 O2 | Homo sapiens | overall reaction | [histone H3]-L-lysine4 + 3 succinate + 3 formaldehyde + 3 CO2 | - |
? | |
| 1.14.11.67 | [histone H3]-N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2 | Homo sapiens | - |
[histone H3]-N6-methyl-L-lysine4 + succinate + formaldehyde + CO2 | - |
? | |
| 1.14.11.67 | [histone H3]-N6-methyl-L-lysine4 + 2-oxoglutarate + O2 | Homo sapiens | - |
[histone H3]-L-lysine4 + succinate + formaldehyde + CO2 | - |
? | |
| 1.14.18.B1 | histone H3 N6,N6-dimethyl-L-lysine27 + 2-oxoglutarate + O2 | Homo sapiens | - |
histone H3 N6-methyl-L-lysine27 + succinate + formaldehyde + CO2 | - |
? | |
| 1.14.18.B1 | additional information | Homo sapiens | enzyme PHF8 binds and stabilizes histone H3 N6,N6,N6-trimethyl-L-lysine4, PHF8 is important in maintaining H3K4me3 levels. PHF8 cooperates with KDM3A | ? | - |
? | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 1.14.11.65 | Homo sapiens | Q9UPP1 | - |
- |
| 1.14.11.65 | Homo sapiens | Q9Y4C1 | - |
- |
| 1.14.11.67 | Homo sapiens | - |
- |
- |
| 1.14.18.B1 | Homo sapiens | Q9UPP1 | - |
- |
Source Tissue
| EC Number | Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|---|
| 1.14.11.65 | HEK-293T cell | - |
Homo sapiens | - |
| 1.14.11.65 | LNCaP cell | - |
Homo sapiens | - |
| 1.14.11.65 | Phoenix-A cell | - |
Homo sapiens | - |
| 1.14.11.65 | prostate gland cancer cell | - |
Homo sapiens | - |
| 1.14.11.65 | RWPE-1 cell | - |
Homo sapiens | - |
| 1.14.11.67 | CWR22-Rv1 cell | - |
Homo sapiens | - |
| 1.14.11.67 | DU-145 cell | - |
Homo sapiens | - |
| 1.14.11.67 | HEK-293T cell | - |
Homo sapiens | - |
| 1.14.11.67 | LNCaP cell | - |
Homo sapiens | - |
| 1.14.11.67 | LNCaP-Abl cell | - |
Homo sapiens | - |
| 1.14.11.67 | PC-3 cell | - |
Homo sapiens | - |
| 1.14.11.67 | Phoenix-AMPHO cell | - |
Homo sapiens | - |
| 1.14.11.67 | RWPE-1 cell | - |
Homo sapiens | - |
| 1.14.18.B1 | LNCaP cell | - |
Homo sapiens | - |
| 1.14.18.B1 | prostate cancer cell | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.14.11.65 | additional information | the bifunctional enzyme catalyzes the demethylation of H3K9me2/me1 and H3K27me3/me2 (EC 1.14.11.68), as well as monomethylated histone H4 Lys20 residue (H4K20Me1). PHF8 acts upstream of KDM3A to regulate specific hypoxia-induced NED markers | Homo sapiens | ? | - |
? | |
| 1.14.11.65 | [histone H3]-N6,N6-dimethyl-L-lysine 9 + 2-oxoglutarate + O2 | - |
Homo sapiens | [histone H3]-N6-methyl-L-lysine 9 + succinate + formaldehyde + CO2 | - |
? | |
| 1.14.11.65 | [histone H3]-N6-methyl-L-lysine 9 + 2-oxoglutarate + O2 | - |
Homo sapiens | [histone H3]-L-lysine 9 + succinate + formaldehyde + CO2 | - |
? | |
| 1.14.11.65 | [histone H4]-N6-methyl-L-lysine 20 + 2-oxoglutarate + O2 | - |
Homo sapiens | [histone H4]-L-lysine 20 + succinate + formaldehyde + CO2 | - |
? | |
| 1.14.11.67 | [histone H3]-N6,N6,N6-trimethyl-L-lysine4 + 2-oxoglutarate + O2 | - |
Homo sapiens | [histone H3]-N6,N6-dimethyl-L-lysine4 + succinate + formaldehyde + CO2 | - |
? | |
| 1.14.11.67 | [histone H3]-N6,N6,N6-trimethyl-L-lysine4 + 3 2-oxoglutarate + 3 O2 | overall reaction | Homo sapiens | [histone H3]-L-lysine4 + 3 succinate + 3 formaldehyde + 3 CO2 | - |
? | |
| 1.14.11.67 | [histone H3]-N6,N6-dimethyl-L-lysine4 + 2-oxoglutarate + O2 | - |
Homo sapiens | [histone H3]-N6-methyl-L-lysine4 + succinate + formaldehyde + CO2 | - |
? | |
| 1.14.11.67 | [histone H3]-N6-methyl-L-lysine4 + 2-oxoglutarate + O2 | - |
Homo sapiens | [histone H3]-L-lysine4 + succinate + formaldehyde + CO2 | - |
? | |
| 1.14.18.B1 | histone H3 N6,N6-dimethyl-L-lysine27 + 2-oxoglutarate + O2 | - |
Homo sapiens | histone H3 N6-methyl-L-lysine27 + succinate + formaldehyde + CO2 | - |
? | |
| 1.14.18.B1 | additional information | enzyme PHF8 binds and stabilizes histone H3 N6,N6,N6-trimethyl-L-lysine4, PHF8 is important in maintaining H3K4me3 levels. PHF8 cooperates with KDM3A | Homo sapiens | ? | - |
? | |
| 1.14.18.B1 | additional information | the enzyme also demethylates mono- and dimethylated H3 Lys9 (H3K9Me1/2) and monomethylated histone H4 Lys20 residue (H4K20Me1) | Homo sapiens | ? | - |
? | |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 1.14.11.65 | histone demethylase | - |
Homo sapiens |
| 1.14.11.65 | PHF8 | - |
Homo sapiens |
| 1.14.11.67 | PHD finger protein 8 | - |
Homo sapiens |
| 1.14.11.67 | PHF8 | - |
Homo sapiens |
| 1.14.18.B1 | histone demethylase | - |
Homo sapiens |
| 1.14.18.B1 | PHD finger protein 8 | - |
Homo sapiens |
| 1.14.18.B1 | PHF8 | - |
Homo sapiens |
Expression
| EC Number | Organism | Comment | Expression |
|---|---|---|---|
| 1.14.11.65 | Homo sapiens | treatment by hypoxia (1% O2, 6 days) but not by androgen deprivation or interleukin-6, leads to posttranscriptional upregulation of PHF8 in LNCaP cells | up |
General Information
| EC Number | General Information | Comment | Organism |
|---|---|---|---|
| 1.14.11.65 | malfunction | PHF8 knockout inhibits the hypoxic activation of HIF1alpha protein, and attenuates the upregulation of KDM3A and ENO2 proteins. The fact that PHF8 knockdown by shRNAs in LNCaP cells does not affect HIF1A mRNA when compared with the impaired activation of HIF1alpha protein suggests that PHF8 indirectly regulates HIF1alpha protein | Homo sapiens |
| 1.14.11.65 | physiological function | histone demethylase PHF8 plays an essential role in hypoxia signaling. Knockdown or knockout of PHF8 reduces the activation of HIF1alpha and the induction of HIF1alpha target genes including KDM3A. PHF8 regulates hypoxia inducible genes mainly through sustaining the level of trimethylated histone 3 lysine 4 (H3K4me3). The positive role of PHF8 in hypoxia signaling extends to hypoxia-induced neuroendocrine differentiation, wherein PHF8 cooperates with KDM3A to regulate the expression of neuroendocrine differentiation genes. The role of PHF8 in hypoxia signaling is associated with the presence of full-length androgen receptor in castration-resistant prostate cancer cells | Homo sapiens |
| 1.14.11.65 | physiological function | histone demethylase PHF8 regulates hypoxia signaling through HIF1alpha and H3K4me3. Enzyme PHF8 binds and stabilizes histone H3 N6,N6,N6-trimethyl-L-lysine4, PHF8 is important in maintaining H3K4me3 levels on hypoxia-inducible genes, regulation, overview. PHF8 cooperates with KDM3A (EC 1.14.11.65) and PHF8 plays a role in hypoxia signaling. The regulation of hypoxia signaling by PHF8 is associated with androgen receptor AR status in prostate cancer cells | Homo sapiens |
| 1.14.11.67 | physiological function | the enzyme plays an essential role in hypoxia signaling. The enzyme regulates the expression of hypoxia-induced neuroendocrine differentiation genes. The enzyme is essential for maintaining [histone H3]-N6,N6,N6-trimethyl-L-lysine4 levels on hypoxia-inducible genes. In the context of prostate cancer, the enzyme appears to execute its regulatory function during hypoxia signaling in androgen receptor-positive prostate cancer cells | Homo sapiens |
| 1.14.18.B1 | malfunction | PHF8 knockout by the CRISPR-Cas9 system attenuates hypoxia signaling in 293T cells. Knockdown or knockout of PHF8 by RNAi or CRISPR-Cas9 system reduces the activation of HIF1alpha and the induction of HIF1alpha target genes including KDM3A. Despite the impaired hypoxia induced stabilization of HIF1alpha protein, the upregulation of KDM3A is only attenuated by PHF8 knockout. PHF8 knockdown elevates H3K9me2 at the 3'UTRs of KDM3A, VEGFA and at the TSS of ENO2 under normoxia. Knockdown of PHF8 increases H3K27me2 at the TSS of ENO2 and decreases H3K27me2 at the 3'UTR of ENO2, respective | Homo sapiens |
| 1.14.18.B1 | physiological function | PHF8 regulates hypoxia inducible genes mainly through sustaining the level of trimethylated histone 3 lysine 4 (H3K4me3), an active mark in transcriptional regulation. The positive role of PHF8 in hypoxia signaling extends to hypoxia-induced neuroendocrine differentiation (NED), wherein PHF8 cooperates with KDM3A to regulate the expression of NED genes. The role of PHF8 in hypoxia signaling is associated with the presence of full-length androgen receptor in CRPC cells. PHF8 is an epigenetic factor in hypoxia signaling, and the underlying regulatory mechanisms likely apply to general cancer development involving HIF1alpha. PHF8 regulates hypoxia inducible genes mainly through sustaining the level of trimethylated histone 3 lysine 4 (H3K4me3), an active mark in transcriptional regulation. PHF8 (PHD finger protein 8) is dynamically regulated during the neuroendocrine differentiation that occurs in prostate cancer, and that the c-MYC-miR-22 axis contributes to the regulation of PHF8 in the context of androgen depletion and interleukin-6 treatment. PHF8 plays a critical role in hypoxia signaling as it positively regulates KDM3A which is a critical coactivator of key transcription factor hypoxia-inducible factor 1-alpha, HIF1alpha, indirectly sustains H3K4me3 levels on select hypoxia-inducible genes, and is required for full activation of HIF1alpha through various mechanisms. In the context of prostate cancer, PHF8 appears to execute its regulatory function during hypoxia signaling in androgen receptor-positive prostate cancer cells | Homo sapiens |
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