PHF8 - Histone lysine demethylase PHF8 - human protein (Function)
 
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PHF8 »  Histone lysine demethylase PHF8   [ EC 1.14.11.27 ]
 
Protein also known as:  PHD finger protein 8.
Gene name:  PHF8
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3.  
10
  • CuratedUniProtKB
GO molecular function 
Chromatin bindingdefinition[GO:0003682]  
1
  • IDAUniProtKB
Histone demethylase activitydefinition[GO:0032452]  
1
  • IDAUniProtKB
Histone demethylase activity (H3-K27 specific)definition[GO:0071558]  
2
  • IDAUniProtKB
Histone demethylase activity (H3-K36 specific)definition[GO:0051864]  
2
  • IDAUniProtKB
Histone demethylase activity (H3-K9 specific)definition[GO:0032454]  
5
  • IDAUniProtKB
Histone demethylase activity (H4-K20 specific)definition[GO:0035575]  
2
  • IDAUniProtKB
Iron ion bindingdefinition[GO:0005506]  
1
  • IDAUniProtKB
Methylated histone bindingdefinition[GO:0035064]  
6
  • IDAUniProtKB
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donorsdefinition[GO:0016706]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
4
  • IPIIntAct
  • IPIUniProtKB
Zinc ion bindingdefinition[GO:0008270]  
1
  • IDAUniProtKB
GO biological process 
Brain developmentdefinition[GO:0007420]  
  • ISSOrtholog Curator
G1/S transition of mitotic cell cycledefinition[GO:0000082]  
1
  • IMPUniProtKB
Histone H3-K27 demethylationdefinition[GO:0071557]  
2
  • IDAUniProtKB
Histone H3-K36 demethylationdefinition[GO:0070544]  
2
  • IDAUniProtKB
Histone H3-K9 demethylationdefinition[GO:0033169]  
5
  • IDAUniProtKB
Histone H4-K20 demethylationdefinition[GO:0035574]  
2
  • IDAUniProtKB
Negative regulation of chromatin silencing at rDNAdefinition[GO:0061188]  
1
  • IDAUniProtKB
Oxidation-reduction processdefinition[GO:0055114]  
  • IEAUniProtKB KW
Positive regulation of transcription from RNA polymerase I promoterdefinition[GO:0045943]  
1
  • IDAUniProtKB
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
3
  • IDAUniProtKB
Transcription, DNA-templateddefinition[GO:0006351]  
  • IEAUniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
Protein N(6),N(6)-dimethyl-L-lysine + 2-oxoglutarate + O(2) protein N(6)-methyl-L-lysine + succinate + formaldehyde + CO(2).  
2
  • CuratedUniProtKB
Protein N(6)-methyl-L-lysine + 2-oxoglutarate + O(2) protein L-lysine + succinate + formaldehyde + CO(2).  
2
  • CuratedUniProtKB
It requires the following cofactor
Binds 1 Fe(2+) ion per subunit (Probable).  
2
  • CuratedUniProtKB
Pathways 
According to Reactome, this protein belongs to the following pathway:
Condensation of Prophase Chromosomes  REACT_172744  
 

Biophysicochemical properties

Kinetic parameters
KM 8 uM for histone H3 H3K4me3 and H3K9Me2
KM 134 uM for histone H3 H3K9Me2

Keywords

Biological process 
Cell cycle  definition   [KW-0131]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Activator  definition   [KW-0010]
Chromatin regulator  definition   [KW-0156]
Dioxygenase  definition   [KW-0223]
Oxidoreductase  definition   [KW-0560]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: PHF8
GenomeRNAi: 23133
PRO: PR:Q9UPP1
Chemistry
GuidetoPHARMACOLOGY: 2698