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
EXPRESSION
Type
widely
constitutive of
expressed in
(based on citations)
organ(s)
System
Organ level 1
Organ level 2
Organ level 3
Organ level 4
Level
Pubmed
Species
Stage
Rna symbol
Cardiovascular
heart
highly
Homo sapiens
Reproductive
male system
testis
lowly
Homo sapiens
Urinary
kidney
highly
Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
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
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
