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Symbol PIDD1 contributors: mct - updated : 18-11-2013
HGNC name p53-induced death domain protein 1
HGNC id 16491
Location 11p15.5      Physical location : -
Synonym name
  • leucine-rich repeats and death domain containing
  • Synonym symbol(s) MGC16925, LRDD, PIDD
    TYPE functioning gene
    STRUCTURE 6.07 kb     16 Exon(s)
    MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 splicing 3022 99 910 detected in high abundance in kidney, and heart but only barely in testis 2011 21371439
  • PIDD1
  • molecular switch between the cellular survival pathway and the apoptosis pathway under conditions as damage DNA
  • 16 splicing 3046 83 753 expressed in heart 2011 21371439
  • containing multiple differences in the 5' UTR and coding region compared to variant 1
  • interacts with two other death domain-containing proteins FADD and MADD through their leucine-rich repeats (LRRs)
  • protects cells and inhibits apoptosis induced by PIDD1
  • 16 - 2971 - 893 - 2011 21371439
  • lacking an in-frame coding segment compared to variant 1
  • PIDD3
  • deletion of 17 AAs starting from AA 705, and it cannot induce apoptosis independently, only showing an augmentative pro-apoptotic effect when co-expressed with PIDD1
  • - - - - - . only isoform which is expressed in skeletal muscle, also expressed in testis, ovary, colon, bladder and spleen at high levels . high expression level of mRNA in the testis, ovary, colon, bladder and spleen, not in the heart 2011 21371439
  • contains intron 3 and a 60 bp insert at the 5prime of exon 3
  • lacks the 32 KD N-terminal peptide, missing the LRR domain found in the other three isoforms
  • mainly localizes in the cytoplasm, and produces a relatively higher proportion of PIDD-CC fragment
  • its overexpression independently promotes apoptosis
    Type widely
    constitutive of
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Homo sapiens
    Reproductivemale systemtestis  lowly Homo sapiens
    Urinarykidney   highly Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • 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
    interspecies ortholog to rattus Lrdd_predicted
    ortholog to murine Lrdd
    CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     intracellular
    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
    signaling signal transduction
    a component
    small molecule
  • 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
    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
    corresponding disease(s)
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • 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