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FLASH GENE
Symbol ID4 contributors: SGE - updated : 06-09-2015
HGNC name inhibitor of DNA binding 4, dominant negative helix-loop-helix protein
HGNC id 5363
PROTEIN
PHYSICAL PROPERTIES basic
STRUCTURE
motifs/domains
basic helix-loop-helix (bHLH) motif, lacking the DNA binding basic domain
conjugated PhosphoP
mono polymer heteromer , dimer
HOMOLOGY
interspecies homolog to murine Id4 (98.1pc)
homolog to rattus Id4 (95.7pc)
Homologene
FAMILY
  • basic-helix-loop-helix (BHLH) family of transcription factor
  • inhibitor of DNA-binding (ID) family
    • CATEGORY regulatory , tumor suppressor , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • antagonist of MyoD activity or creatine kinase enhancer
  • may play an important suppressive role in tumor progression, and its silencing by hypermethylation may increase the risk of regional lymph node metastasis
  • promotes osteoblast differentiation by releasing HES1 from HES1-HES2 complexes, thus stabilizing RUNX2 (a key molecule differentiation) (Tokuzawa 2010)
  • inhibiting binding to DNA and transcriptional transactivation by heterodimerization with bHLH proteins (Pagliuca 1995)
  • tumor suppressor in normal breast tissue and epigenetically silenced during cancer development, indicating increased risk for tumor relapse (Noetzel 2008)
  • decreased MMP2 expression by a direct inhibitory interaction with TWIST1, a basic helix-loop-helix transcription factor known to increase MMP2 expression
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
  • binding to and stabilizing mRNAs encoding pro-angiogenic factors IL8 and GRO-alpha (Fontemaggi 2009)
    • small molecule
    protein
  • PRMT5 is required for maintaining the methylation status of CpG islands of ID2 and ID4 leading to gene silencing during glial cell differentiation
  • KCNK10 hyperpolarizes IB4 binding C-nociceptors and limits pathological spontaneous pain
    • cell & other
    REGULATION
    repressed by ZBTB18, repressing ID1, ID2, ID3, ID4 genes during corticogenesis
    Other regulated by BRCA1
    down-regulated by CDC42 through an epigenetic mechanism (Gomez Del Pulzar 2008)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    by promoter hypermethylation in acute myeloid leukemia
    tumoral     --other  
    dysregulated in breast and ovarian carcinomas with BRCA1
    tumoral     --low  
    in breast cancer by aberrant hypermethylation of the promoter region, increasing risk of lymph node metastasis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • ID4 could be efficacious for identifying previously unrecognized human spermatogonial subpopulations in conjunction with other putative human stem cell markers
    • Therapy target
  • ID4 methylation could serve as a prognostic biomarker in breast cancer (Noetzel 2008)
  • may be a therapeutic target in myelodysplastic syndrome (MDS) (Wang 2010)
    • ANIMAL & CELL MODELS