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FLASH GENE
Symbol RAD17 contributors: mct - updated : 30-10-2015
HGNC name RAD17 homolog (S. pombe)
HGNC id 9807
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • potential a N terminal P-loop binding consensus sequence
  • a Walker B motif
  • HOMOLOGY
    interspecies homolog to yeast S.pombe RAD17
    homolog to yeast S.cerevisiae RAD24
    homolog to murine Rad24
    homolog to murine Rad17
    Homologene
    FAMILY
  • rad17/RAD24 family
  • CATEGORY regulatory , DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • cell cycle G2 checkpoint control gene, required for S-phase and G2/M arrest in response to DNA damage or incomplete DNA replication
  • centrally involved in the activation of cell-cycle checkpoints by genotoxic agents or replication stress
  • phosphorylation-dependent function of RAD17 in an ATR-RAD17-Claspin-CHEK1-signaling cascade that responds to specific replication stress
  • similarly to other human genes involved in checkpoint mechanisms, plays a role in control of tumor growth
  • critical for the ATR-dependent activation of CHEK1 during checkpoint responses
  • exhibiting a distinctive pattern of upregulation followed by subsequent degradation after exposure to UV radiation in primary cells
  • its stabilization prevents the termination of checkpoint signalling, which in turn attenuates the cellular re-entry into cell-cycle progression
  • CELLULAR PROCESS cell cycle, checkpoint
    nucleotide, repair
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • RAD17/RAD3/RAD1, is the 9-1-1 complex
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with RAD1 (interaction protein-protein in the cell cycle checkpoint machinery)
  • MCM7, a core component of the DNA replication apparatus, is a novel RAD17-interacting protein
  • phosphorylated RAD17 interacts with Claspin and regulates its phosphorylation
  • plays a central role in establishment of the interaction between TOPBP1 and the RAD9A-HUS1-RAD1 complex at stalled replication forks
  • Claspin and RAD17 are reportedly involved in the DNA damage-induced phosphorylation of CHEK1, a hallmark of checkpoint activation
  • RAD9A is loaded by RAD17 onto damaged chromatin
  • USP20 is required for RAD17 protein stability in the steady-state and post DNA damage
  • gain of function mutant TP53 proteins cooperate with E2F4 to transcriptionally downregulate RAD17 and BRCA1 gene expression
  • cell & other
    REGULATION
    Other phosphorylation by ATR is important for genomic stability and restraint of S phase but is not essential for cell survival
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    in head and neck cancer, is often due to genomic deletion, and may facilitate genomic instability in head and neck cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS