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FLASH GENE
Symbol PIDD1 contributors: mct - updated : 18-11-2013
HGNC name p53-induced death domain protein 1
HGNC id 16491
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • six leucine rich repeats (LRR) at N terminus
  • a death domain (DD) at C terminus processed in two fragments containing LRR (33kDa) and DD (55kDa), fragment containing the PIDD death domain that shuttles into the nucleoli, and ATM phosphorylation of the PIDD DD enables a binary switch through which cells elect to survive or die upon DNA injury
  • a CARD domain
  • HOMOLOGY
    interspecies ortholog to rattus Lrdd_predicted
    ortholog to murine Lrdd
    Homologene
    FAMILY
    CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • may function as an adaptor protein in cell death-related signaling processes
  • acting as a molecular switch, controlling the balance between life and death upon DNA damage
  • playing a role in the activation of NF-kappaB upon genotoxic stress
  • PIDD with CRADD, is implicated in the activation of pro-caspase-2 in a high molecular weight complex called the PIDDosome during apoptosis induction after DNA damage
  • does not play an essential role for all TP53-mediated or TP53-independent apoptotic pathways
  • implicated in survival and apoptotic pathways in response to DNA damage, and having a role in non-homologous end-joining (NHEJ) repair induced by gamma-irradiation
  • orchestrates translesion DNA synthesis in response to UV irradiation
  • has been implicated in TP53-mediated cell death in response to DNA damage but also in DNA repair and nuclear factor kappa-light-chain enhancer (NFKB1) activation upon genotoxic stress
  • death-domain (DD) protein implicated as a molecular switch capable of signaling cell survival or death in response to genotoxic stress
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • FADD and MADD (death domain containing proteins)
  • death receptor
  • caspase 2 via the CARD domain
  • TPp53 target gene whose main role is to execute apoptosis in a TP53-dependent manner
  • interacting with HSP90AA1 (HSP90AA1 has a major role in controlling PIDD functional activity)
  • cell & other
    REGULATION
    induced by TP53, and was able to promote apoptosis
    Phosphorylated by ATM that phosphorylates PIDD1 on Thr788 within the DD domain
    Other auto-proteolysis of PIDD might participate in the orchestration of the DNA damage-induced life and death signaling pathways
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Pidd-deficient mice undergo apoptosis normally not only in response to DNA damage, but also in response to various Tp53-independent stress signals and to death receptor (DR) engagement