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FLASH GENE
Symbol PELI3 contributors: mct/npt - updated : 11-03-2015
HGNC name pellino homolog 3 (Drosophila)
HGNC id 30010
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a new RING-like motif
  • a noncanonical forkhead-associated (FHA) domain, a well-characterized phosphothreonine-binding module
    • HOMOLOGY
    intraspecies homolog to PELI1, PELI3
    Homologene
    FAMILY
  • Pellino protein family
    • CATEGORY immunity/defense , structural protein
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • promoting activation of C-Jun and ELK-1 and may be acting as a scaffolding protein
  • playing an important role in the innate immune response
  • implicated as evolutionary conserved scaffold proteins in TLR/IL-1R signaling leading to nuclear factor-kappaB and mitogen activated protein kinase-dependent gene expression
  • E3 ligases that can catalyze Lys(63)-linked polyubiquitination but also shows bidirectional signaling between the IRAK and Pellino families and highlights a novel function for IRAK kinase activity
  • PELI1, PELI2, PELI3 are novel RING E3 ubiquitin ligases involved in IRAK1 polyubiquitination and degradation
  • PELI2, PELI3 (to a much lesser degree Pellino 1) carry the E3 ubiquitin ligase activity and promote polyubiquitination on IRAK1
  • induce IRAK1 polyubiquitination in a RING-dependent manner
  • is a novel regulator of TNF signalling and an important determining factor in dictating whether TNF induces cell survival or death
  • PELI1, PELI2, PELI3 E3 ubiquitin ligases are emerging as critical mediators for a variety of immune signaling pathways, including those activated by Toll-like receptors, the T-cell receptor, and NOD2
  • nonredundant roles that PELI1, PELI2, PELI3 play in immune signaling are in part due to their divergent substrate specificities
  • E3 ubiquitin ligase and scaffold protein in TLR4-signaling, impacted by autophagy in macrophages after LPS stimulation
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with IL-1R-associated kinase-1, TNF receptor-associated factor-6, TGF-beta-activated kinase-1, and NF-kappaB-inducing kinase in an IL-1-dependent manner
  • strong activator of MAPK14 (upstream regulator of the p38 MAPK pathway but also probes the mechanistic basis underlying the ability of PELI3 to promote activation of this pathway)
  • IRAK1-binding region of PELI1, PELI2, PELI3 proteins consists largely of a previously unidentified forkhead-associated (FHA) domain
  • regulatory impact of IRAK1/4 and PELI3 on the TICAM1-dependent TLR4-signaling cascade, which might be of general importance for disease conditions associated with macrophage pathologies such as atherosclerosis
  • targets the IRF7 pathway and facilitates autoregulation of TLR3- and viral-induced expression of type I interferons
  • RIPK2 is a substrate for PELI3 and PELI3 is an important mediator in the NOD2 pathway and regulator of intestinal inflammation
  • PELI3 targets RIPK1, in a TNF-dependent manner, to inhibit TNF-induced complex II formation
  • autophagy-dependent PELI3 degradation inhibits proinflammatory IL1B expression
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS