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FLASH GENE
Symbol PHF8 contributors: mct - updated : 10-10-2017
HGNC name PHD finger protein 8
HGNC id 20672
Corresponding disease
MRXSSD Siderius mental retardation syndrome
Location Xp11.22      Physical location : 53.963.113 - 54.071.569
Synonym name
  • homo sapiens KIAA1111 protein mRNA
  • PHD zinc finger
  • jumonji C domain-containing histone demethylase 1F
    • Synonym symbol(s) KIAA1111, ZNF422, JHDM1F, DKFZp686E0868, KDM7B
    EC.number 1.14.11.27
    DNA
    TYPE functioning gene
    STRUCTURE 108.46 kb     22 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    22 - 6072 113.9 1024 - 2010 20622854
    22 - 5921 - 1060 - 2010 20622854
    22 - 4667 - 948 - 2010 20622854
    22 - 3580 - 878 - 2010 20622854
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   highly
    Lymphoid/Immunelymph node   highly
    Reproductivefemale systemuteruscervix moderately
     female systemovary  moderately
     male systemtestis  moderately
     male systemprostate  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a plant homeodomain (PHD) in its N terminus
  • five nuclear localization signal
  • a JmjC C-terminal domain, which can catalyze lysine demethylation
  • a catalytic domain that is a 2-oxoglutarate oxygenase with selectivity for H3K9me2/me1, H3K27me2 and H3K36me2 AAs
    • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Phf8
    Homologene
    FAMILY
  • family of JmjC domain-containing proteinsa PHD-type zinc finger
    • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    text
  • localized in the nucleolus and may regulate rRNA transcription
    • basic FUNCTION
  • involved in the regulation of transcription, DNA-dependent
  • histone lysine demethylase selective for the di- and mono-methyl states
  • histone methylation modulated by PHF8 plays a critical role in neuronal differentiation
  • possible role for PHF8 in regulation of cell growth via histone demethylation
  • PHD and Jumonji C (JmjC) domain-containing protein, functioning as an H4K20me1 demethylase
  • intimate link between this enzyme and two distinct events in cell cycle progression
  • can act as a transcriptional coactivator and that its activation function largely depends on binding of the PHD to H3K4me3
  • co-activator function having important functional roles in neuronal development
  • transcriptional co-activator involved in cell cycle progression
  • plays an important role in transcriptional activation of key G2/M genes during G2 phase
  • not only activates but may also repress gene expression
  • is involved in the development of several types of cancer, including leukemia, prostate cancer, and esophageal squamous cell carcinoma
  • PHF2, PHF8, possess a PHD domain-dependent di-/trimethylated histone 3 lysine 4 (H3K4me2/3) binding activity and are known to be enriched in the nucleolus
  • PHF8 serves as an endogenous factor that the host uses to attenuate cardiac hypertrophy upon cardiac overload (pMID: 25921086)
  • regulates mesodermal lineage and cell fate decisions in differentiating mESCs through epigenetic control of the gene critical to programmed cell death pathways
  • plays important roles in breast cancer cell migration and tumor growth
  • in addition to its well-characterized function as a coactivator, PHF8 safeguards transcription to allow an accurate immune response
  • catalyzes demethylation of mono- and di-methylated Lys9 on histone H3 (H3K9me1/2), and is a transcriptional activator involved in the development and cancer
  • is a histone demethylase with specificity for repressive modifications
  • plays an essential role in hypoxia signaling
  • positive role of PHF8 in hypoxia signaling extended to hypoxia-induced neuroendocrine differentiation (NED), wherein PHF8 cooperates with KDM3A to regulate the expression of NED genes
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • interacts with ZNF711, which binds to a subset of PHF8 target genes, including the XLMR gene KDM5C
  • direct interaction of PHF8 with the C-terminal domain of POLR2A
  • interacts with RARalpha and functions as a coactivator for RARalpha
  • direct interaction of PHF8 with the C-terminal domain of RNA Polymerase II
  • PHF2 is likely to repress rDNA transcription by competing with PHF8 for binding of rDNA promoter and by recruiting H3K9me2/3 methyltransferase SUV39H1
  • PHF8 by controlling E2F4 expression maintains endothelial function
  • direct link between PHF8 expression and serotonin signalling
  • regulates hypoxia inducible genes mainly through sustaining the level of trimethylated histone 3 lysine 4 (H3K4me3), an active mark in transcriptional regulation
    • cell & other
    REGULATION
    Other activity of endogenous PHF strictly regulated by signaling pathways and switched on in a tissue-, time-, and/or locus-specific manner
    is regulated by CDC20 and plays an important role in the G2/M transition
    ASSOCIATED DISORDERS
    corresponding disease(s) MRXSSD
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    can potentially be a novel therapeutic strategy in cancer therapy
    cancerreproductivebreast
    promising therapeutic target for breast cancer
    cardiovascularcardiomyopathy 
    enhancement might be of benefit in the treatment of hypertrophic cardiomyopathy
    ANIMAL & CELL MODELS
  • regulates cell survival in the zebrafish brain and jaw development, in part by directly regulating the expression of the homeodomain transcription factor MSX1/MSXB, which functions downstream of multiple signalling and developmental pathways
  • Phf8 deficient mice neither display obvious developmental defects nor signs of cognitive impairment, but a striking resiliency to stress-induced anxiety- and depression-like behaviour on loss of Phf8