Tchem PHF8 Histone lysine demethylase PHF8

Protein Summary

Description

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. The protein encoded by this gene is a histone lysine demethylase that preferentially acts on histones in the monomethyl or dimethyl states. The encoded protein requires Fe(2+) ion, 2-oxoglutarate, and oxygen for its catalytic activity. The protein has an N-terminal PHD finger and a central Jumonji C domain. This gene is thought to function as a transcription activator. Defects in this gene are a cause of syndromic X-linked Siderius type intellectual disability (MRXSSD) and over-expression of this gene is associated with several forms of cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

Uniprot Accession IDs

• Q9UPP1
• B3KMV4
• B7Z911
• Q5H9U5
• Q5JPR9
• Q5JPS0
• Q5JPS2
• Q5JPS3
• Q5VUJ4
• Q7Z6D4
• Q9HAH2

Gene Name

• PHF8

Ensembl ID

• ENST00000322659
• ENSP00000319473
• ENSG00000172943
• ENST00000338154
• ENSP00000338868
• ENST00000338946
• ENSP00000340051
• ENST00000357988
• ENSP00000350676

Symbol

• KIAA1111
• ZNF422
• KDM7B
• JHDM1F
• MRXSSD
• ZNF422

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein complex	0.95
microRNA	0.89
protein domain	0.85
molecular function	0.81
biological process	0.79

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 71.35   (req: < 5)

Gene RIFs: 46   (req: <= 3)

Antibodies: 105   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 71.35   (req: >= 5)

Gene RIFs: 46   (req: > 3)

Antibodies: 105   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 19

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 51

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0