background:
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. Defects in this gene are a cause of mental retardation syndromic X-linked Siderius type (MRXSSD). Four transcript variants encoding different isoforms have been found for this gene.
Function:
Histone lysine demethylase with selectivity for thedi-and monomethyl states that plays a key role cell cycleprogression, rDNA transcription and brain development. Demethylatesmono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 andH3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylatedhistone H4 'Lys-20' residue (H4K20Me1). Acts as a transcriptionactivator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigeneticrepressive marks. Involved in cell cycle progression by beingrequired to control G1-S transition. Acts as a coactivator of rDNAtranscription, by activating polymerase I (pol I) mediatedtranscription of rRNA genes. Required for brain development,probably by regulating expression of neuron-specific genes. Onlyhas activity toward H4K20Me1 when nucleosome is used as a substrateand when not histone octamer is used as substrate. May also haveweak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however,the relevance of this result remains unsure in vivo. Specificallybinds trimethylated 'Lys-4' of histone H3 (H3K4me3), affectinghistone demethylase specificity: has weak activity toward H3K9Me2in absence of H3K4me3, while it has high activity toward H3K9me2when binding H3K4me3.
Subunit:
Interacts with POLR1B, UBTF, SETD1A, HCFC1, E2F1 andZNF711.
Subcellular Location:
Nucleus. Nucleus, nucleolus. Note=Recruitedto H3K4me3 sites on chromatin during interphase. Dissociates fromchromatin when cells enter mitosis.
Post-translational modifications:
Phosphorylation at Ser-69 and Ser-120 are required fordissociation from chromatin and accumulation of H4K20Me1 levelsduring prophase.
DISEASE:
Defects in PHF8 are the cause of mental retardationsyndromic X-linked Siderius type (MRXSSD) [MIM:300263]. A disordercharacterized by mild to borderline mental retardation with orwithout cleft lip/cleft palate.
Similarity:
Belongs to the JHDM1 histone demethylase family.JHDM1D subfamily.
Contains 1 JmjC domain.
Contains 1 PHD-type zinc finger.
Database links:
UniProtKB/Swiss-Prot: Q9UPP1.3
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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