Summary

Name PHF8
Full Name Histone lysine demethylase PHF8
Synonyms EC 1.14.11.27, EC 1.14.11.65, PHD finger protein 8, [histone H3]-dimethyl-L-lysine(36, [histone H3]-dimethyl-L-lysine(9 | KIAA1111, ZNF422
Primary ID Q9UPP1
Links - -
Type protein
Relations 5
Function 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. Positively modulates transcription of histone demethylase KDM5C, acting synergistically with transcription factor ARX; synergy may be related to enrichment of histone H3K4me3 in regulatory elements. {ECO:0000269|PubMed:19843542, ECO:0000269|PubMed:20023638, ECO:0000269|PubMed:20101266, ECO:0000269|PubMed:20208542, ECO:0000269|PubMed:20346720, ECO:0000269|PubMed:20421419, ECO:0000269|PubMed:20531378, ECO:0000269|PubMed:20548336, ECO:0000269|PubMed:20622853, ECO:0000269|PubMed:20622854, ECO:0000269|PubMed:31691806}.

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Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates activity img/direct-activation.png phosphorylation PHF8 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png chemical activation PHF8 0.8
Publications: 1
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination PHF8 0.309
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png binding PHF8 0.345
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png binding TOPBP1 0.2
Publications: 1 Organism: Homo Sapiens