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FLASH GENE
Symbol RFWD3 contributors: mct - updated : 01-03-2012
HGNC name ring finger and WD repeat domain 3
HGNC id 25539
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an SQ-rich region in the N terminus
  • a coil-coil domain
  • a RING domain functioning as E3 ubiquitin ligase
  • C terminus of RFWD3, which encompass the coiled-coil domain and the three WD40 domains, is necessary for binding to RPA
    • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • TP53 E3 ubiquitin ligase and RFWD3-MDM2 complex restricts the polyubiquitination of TP53 by MDM2
  • positive regulator of TP53 stability when the G(1) cell cycle checkpoint is activated
  • novel replication protein A (RPA)-associated protein
  • important for ATR-dependent CHEK1 activation in response to replication stress
  • new player involved in DNA replication checkpoint control
  • recruited to stalled replication forks and co-localizes with RPA2 in response to replication stress
  • recruited to sites of DNA damage and facilitates RPA-mediated DNA damage signaling and repair
  • may play a more direct role in DNA damage repair through its interaction with RPA, suggesting RFWD3 acts as a potential tumor suppressor
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • forms a complex with MDM2 and TP53 to synergistically ubiquitinate TP53 and is required to stabilize TP53 in the late response to DNA damage
  • direct interaction between RPA2 and RFWD3 (RFWD3 is recruited to stalled replication forks and co-localizes with RPA2 in response to replication stress)
  • physically associated with RPA and rapidly localizes to sites of DNA damage in a RPA-dependent manner
    • cell & other
    REGULATION
    Phosphorylated by ATM/ATR kinases
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS