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FLASH GENE
Symbol PELI3 contributors: mct/npt - updated : 11-03-2015
HGNC name pellino homolog 3 (Drosophila)
HGNC id 30010
Location 11q13.2      Physical location : 66.234.335 - 66.244.807
Synonym name pellino 3 alpha
Synonym symbol(s) MGC35521
DNA
TYPE functioning gene
STRUCTURE 11.01 kb     8 Exon(s)
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
8 - 2763 50.7 469 - 2008 18326498
pellino3A
7 - 2691 - 445 - 2008 18326498
  • pellino3B
  • missing an exon (exon 3, 24 amino acids)/ Pellino3A
  • acting as a negative regulator for IL1 signaling by regulating IRAK degradation through its E3 ligase activity
  • being a RING-like E3 Ubiquitin Ligase
  • plays a negative role in IL1B-induced NR2C2-dependent NFKB activation
  • acts as a negative regulator for IL1 signaling by regulating IRAK1 degradation through its ubiquitin protein ligase activity.
  • 7 - 2530 - 406 - 2008 18326498
    6 - 2538 - 362 - 2008 18326498
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineneuroendocrinepituitary  highly
    Nervousnerve   highly
    Reproductivefemale systemovary  highly
     female systemuteruscervix highly
    Respiratorylung    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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