Description: Homo sapiens PHD finger protein 8 (PHF8), transcript variant 1, mRNA. RefSeq Summary (NM_001184896): 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]. Transcript (Including UTRs) Position: hg19 chrX:53,963,113-54,071,569 Size: 108,457 Total Exon Count: 22 Strand: - Coding Region Position: hg19 chrX:53,965,591-54,071,323 Size: 105,733 Coding Exon Count: 22
ID:PHF8_HUMAN DESCRIPTION: RecName: Full=Histone lysine demethylase PHF8; EC=1.14.11.27; AltName: Full=PHD finger protein 8; 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. CATALYTIC ACTIVITY: Protein N(6),N(6)-dimethyl-L-lysine + 2- oxoglutarate + O(2) = protein N(6)-methyl-L-lysine + succinate + formaldehyde + CO(2). CATALYTIC ACTIVITY: Protein N(6)-methyl-L-lysine + 2-oxoglutarate + O(2) = protein L-lysine + succinate + formaldehyde + CO(2). COFACTOR: Binds 1 Fe(2+) ion per subunit (Probable). BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=134 uM for histone H3 H3K9Me2; KM=8 uM for histone H3 H3K4me3 and H3K9Me2; SUBUNIT: Interacts with POLR1B, UBTF, SETD1A, HCFC1, E2F1 and ZNF711. SUBCELLULAR LOCATION: Nucleus. Nucleus, nucleolus. Note=Recruited to H3K4me3 sites on chromatin during interphase. Dissociates from chromatin when cells enter mitosis. DOMAIN: The PHD-type zinc finger mediates the binding to H3K4me3. Binding to H3K4me3 promotes its access to H3K9me2. DOMAIN: The linker region is a critical determinant of demethylase specificity. It enables the active site of JmjC to reach the target H3K9me2 when the PHD-type zinc finger binds to H3K4me3. PTM: Phosphorylation at Ser-69 and Ser-120 are required for dissociation from chromatin and accumulation of H4K20Me1 levels during prophase. DISEASE: Defects in PHF8 are the cause of mental retardation syndromic X-linked Siderius type (MRXSSD) [MIM:300263]. A disorder characterized by mild to borderline mental retardation with or without cleft lip/cleft palate. SIMILARITY: Belongs to the JHDM1 histone demethylase family. JHDM1D subfamily. SIMILARITY: Contains 1 JmjC domain. SIMILARITY: Contains 1 PHD-type zinc finger. SEQUENCE CAUTION: Sequence=BAA83063.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=BAB13877.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=CAI41577.1; Type=Erroneous gene model prediction; Sequence=CAI41581.1; Type=Erroneous gene model prediction; Sequence=CAI41582.1; Type=Erroneous gene model prediction; Sequence=CAI42861.1; Type=Erroneous gene model prediction; Sequence=CAI45929.1; Type=Erroneous termination; Positions=419; Note=Translated as Arg;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9UPP1
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0003682 chromatin binding GO:0005506 iron ion binding GO:0005515 protein binding GO:0008270 zinc ion binding GO:0016491 oxidoreductase activity GO:0016706 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 donors GO:0032452 histone demethylase activity GO:0032454 histone demethylase activity (H3-K9 specific) GO:0035064 methylated histone binding GO:0035575 histone demethylase activity (H4-K20 specific) GO:0046872 metal ion binding GO:0051213 dioxygenase activity GO:0051864 histone demethylase activity (H3-K36 specific) GO:0071558 histone demethylase activity (H3-K27 specific)
Biological Process: GO:0000082 G1/S transition of mitotic cell cycle GO:0006325 chromatin organization GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0007049 cell cycle GO:0007420 brain development GO:0033169 histone H3-K9 demethylation GO:0035574 histone H4-K20 demethylation GO:0045893 positive regulation of transcription, DNA-templated GO:0045943 positive regulation of transcription from RNA polymerase I promoter GO:0055114 oxidation-reduction process GO:0061188 negative regulation of chromatin silencing at rDNA GO:0070544 histone H3-K36 demethylation GO:0071557 histone H3-K27 demethylation
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