PHF8 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. Belongs to the JHDM1 histone demethylase family. JHDM1D subfamily. 5 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Demethylase; EC; Nucleolus
Chromosomal Location of human Ortholog: Xp11.22
Cellular Component:  nuclear membrane; nucleolus; nucleoplasm; nucleus
Molecular Function:  2-oxoglutarate-dependent dioxygenase activity; chromatin binding; histone demethylase activity; histone H3K27me2/H3K27me3 demethylase activity; histone H3K36 demethylase activity; histone H3K36me/H3K36me2 demethylase activity; histone H3K9 demethylase activity; histone H3K9me/H3K9me2 demethylase activity; histone H4K20 demethylase activity; iron ion binding; methylated histone binding; protein binding; transcription coregulator activity; zinc ion binding
Biological Process:  brain development; chromatin remodeling; DNA-templated transcription; G1/S transition of mitotic cell cycle; negative regulation of rDNA heterochromatin formation; positive regulation of DNA-templated transcription; positive regulation of transcription by RNA polymerase I; positive regulation of transcription by RNA polymerase II; protein demethylation; regulation of transcription by RNA polymerase II
Disease: Siderius X-linked Mental Retardation Syndrome
Reference #:  Q9UPP1 (UniProtKB)
Alt. Names/Synonyms: [histone H3]-dimethyl-L-lysine(36) demethylase PHF8; [histone H3]-dimethyl-L-lysine(9) demethylase PHF8; DKFZp686E0868; Histone lysine demethylase PHF8; JHDM1F; jumonji C domain-containing histone demethylase 1F; KDM7B; KIAA1111; MRXSSD; PHD finger protein 8; PHF8; ZNF422
Gene Symbols: PHF8
Molecular weight: 117,864 Da
Basal Isoelectric point: 8.92  Predict pI for various phosphorylation states
CST Pathways:  Histone Methylation
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
Select Structure to View Below


Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  cBioPortal  |  Wikipedia  |  neXtProt  |  Protein Atlas  |  BioGPS  |  Pfam  |  RCSB PDB  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  Ensembl Protein