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FLASH GENE
Symbol WHSC1 contributors: mct/pgu - updated : 18-02-2012
HGNC name Wolf-Hirschhorn syndrome candidate 1
HGNC id 12766
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo
Text preferentially in rapidly growing tissues
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a nuclear localization signal (NLS)
  • two PWWP (proline-2 tryptophan-proline)domains (one in N-terminus)
  • a HMG2 box, four PHD-type zinc fingers and a multifunctional chromatin regulator (130 AA) SET domain (Suvar, Enhancer of zest, Trithorax)
  • C-terminal SET domain characteristic of histone methyltransferases
  • HOMOLOGY
    interspecies homolog to Drosophila dysmorphy gene ash
    homolog to murine Whsc1l
    Homologene
    FAMILY
  • histone-lysine methyltransferase family
  • SET2 subfamily
  • nuclear receptor binding SET domain (NSD) protein family
  • CATEGORY enzyme , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • having ubiquitin-protein ligase activity
  • could be implicated in tumor emergence and/or progression
  • potentially acts as a pathogenic agent in many cancers
  • by acting directly as a modifier of chromatin as well as through binding of other chromatin modifying enzymes, may influence gene expression and potentially acts as a pathogenic agent in multiple myeloma
  • major regulator of chromatin structure and transcription in t(4;14) multiple myeloma cells
  • has a role in the DNA damage response
  • critical role of WHSC1 in regulating the assembly of TP53BP1 foci at DNA lesions
  • required for proliferation of neuroblastoma cells and brain-derived neural stem cells
  • critical in maintaining the chromatin integrity
  • dimethylation of histone H3 at lysine 36 (H3K36me2) is the principal chromatin-regulatory activity of WHSC1
  • EZH2 mediates histone H3K27 trimethylation and is associated with gene silencing, coordinately expressed and function upstream of WHSC1, which mediates H3K36 dimethylation and is associated with active transcription
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
  • pathway involving H2AFX–MDC1–WHSC1 regulates the induction of H4K20 methylation on histones around DSBs, which, in turn, facilitates TP53BP1 recruitment
  • a component
  • component of transcription co-repressor complexes (HDAC1 and HDAC2, SIN3A and the histone demethylase AOF2)
  • EZH2-WHSC1 HMTase axis coordinately functions as a master regulator of transcriptional repression, activation, and oncogenesis
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • IL5 (suppression of transcription)
  • upstream regulator of TP53BP1
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) WHS , WHSCR
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    fused to IgH in multiple myeloma with translocation t(4;14)((p16.3;q32) with FGFR3 overexpression
    tumoral     --over  
    in multiple myeloma with poor prognosis, in patients with the translocation t(4;14)
    tumoral somatic mutation      
    in acute myeloid leukemia
    tumoral     --other  
    aberrant expression in glioblastoma multiform
    constitutional     --low  
    resulted in cellular hypersensitivity to ionizing radiation
    tumoral     --over  
    in neuroblastoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene Wolf-Hirschhorn syndrome candidate gene 1
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerbrainglioma/neuroblstoma
    might be a strong candidate therapeutic target in a subset of neuroblastomas with unfavorable prognosis
    ANIMAL & CELL MODELS