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FLASH GENE
Symbol PELI1 contributors: mct/npt/pgu - updated : 15-12-2017
HGNC name pellino E3 ubiquitin protein ligase 1
HGNC id 8827
Location 2p15      Physical location : 64.319.787 - 64.371.605
Synonym name
  • Pelle-interacting protein 1
  • Pellino-related intracellular- signaling molecule
  • Synonym symbol(s) MGC50990, DKFZp686C18116, PRISM
    EC.number 2.3.2.27
    DNA
    TYPE functioning gene
    STRUCTURE 51.82 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC391376 2 similar to 60S ribosomal protein L14 (CAG-ISL 7) FLJ13305 2p15 hypothetical protein FLJ13305 CCT4 2p13.3 chaperonin containing TCP1, subunit 4 (delta) C2orf5 2p15 chromosome 2 open reading frame 5 (MURR1) LOC388954 2 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) (Colon carcinoma laminin-binding protein) (NEM/1CHD4) (Multidrug resistance-associated protein MGr1-Ag) B3GNT1 2p14 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 1 FLJ34583 KIAA0903 2p15 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 1 OTX1 2p13 orthodenticle homolog 1 (Drosophila) LOC51057 2p15 hypothetical protein LOC51057 MDH1 2p16 malate dehydrogenase 1, NAD (soluble) LOC388955 2 similar to Px19-like protein (25 kDa protein of relevant evolutionary and lymphoid interest) (PRELI) (CGI-106) (SBBI12) LOC391377 2 similar to ribosomal protein S4 LOC391378 2 similar to Heterogeneous nuclear ribonucleoprotein A1 (Helix-destabilizing protein) (Single-strand binding protein) (hnRNP core protein A1) (HDP-1) (Topoisomerase-inhibitor suppressed) UGP2 2p14-p13 UDP-glucose pyrophosphorylase 2 VPS54 2p13-p14 vacuolar protein sorting 54 (yeast) PELI1 2p13.3 pellino homolog 1 (Drosophila) LOC130773 2p15 similar to 60S ribosomal protein L23a HSPC159 2p15 HSPC159 protein FLJ20080 2p15 hypothetical protein FLJ20080 TRIP-Br2 2p15 transcriptional regulator interacting with the PHS-bromodomain 2 SLC1A4 2p13.3 solute carrier family 1 (glutamate/neutral amino acid transporter), member 4 LOC200731 2p14 hypothetical LOC200731 KIAA0582 2p14 hypothetical LOC200731 RAB1A 2p14 RAB1A, member RAS oncogene family LOC150984 2p14 similar to voltage-dependent anion channel isoform 2 ACTR2 2p14 ARP2 actin-related protein 2 homolog (yeast) SPRED2 2p14 sprouty-related, EVH1 domain containing 2 LOC388956 2 LOC388956 LOC391379 2 similar to DnaJ homolog subfamily B member 12 LOC391380 2 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 3780 - 418 - 2007 17675297
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen    
    Cardiovascularheart    
    Lymphoid/Immunelymph node   highly
    Nervousnerve   highly
    Reproductivemale systemprostate   
    Respiratoryrespiratory tracttrachea  highly
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a partial zinc finger (C3HC4 type or RING finger)
  • a new RING-like motif
  • IRAK1-binding region consists largely of a previously unidentified forkhead-associated (FHA) domain, a well-characterized phosphothreonine-binding modules
  • a putative C terminal nuclear localization signal (NLS)
  • HOMOLOGY
    interspecies homolog to murine Peli1
    ortholog to Drosophila pli
    homolog to C.elegans f25b4.2
    Homologene
    FAMILY
  • Pellino family
  • CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text translocate in the nucleus
    basic FUNCTION
  • ubiquitin-protein isopeptide ligase, required for NF kappa B activation and IL-8 gene expression in response to IL-1, probably through its signal-dependent interaction with IRAK4, IRAK, TRAF6
  • 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
  • RING E3 ubiquitin ligases involved in signaling events downstream of the Toll and interleukin-1 (IL1) receptors, key initiators of innate immune and inflammatory responses
  • induce IRAK1 polyubiquitination in a RING-dependent manner
  • PELI1 and PELI2 appear to function as positive regulators for NFKB activation
  • ubiquitin ligase needed for the transmission of TICAM1-dependent TLR signals
  • 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
  • Pellino1 is a novel component of the signal transduction network by which viral double-stranded RNA stimulates IFNB1 gene transcription
  • PELI1 interacts with the transcription factor DEAF1, and this interaction is independent of the E3 ligase activity of PELI1, but weakened by the phosphorylation of PELI1
  • 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
  • promotes lymphomagenesis by deregulating BCL6 polyubiquitination
  • previously unrecognized role of PELI1 in extracellular matrix deposition and cardiac fibroblast activation in response to mechanical stress
  • is an innate immune regulator in the CNS that modulates the threshold of IFN1 responses against viral infections
  • play a pivotal role in inflammatory processes through the activation of Toll-like receptor signaling and the NFKB1 pathway
  • might participate in B-cell maturation or oncogenic activation of aggressive B-cell lymphomas, both during and after germinal center stages
  • PELI1 is a key modulator of RIPK1 that differentially controls the activation of necroptosis and apoptosis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • associate with and ubiquitinate proteins, including the interleukin-1 receptor associated kinase-1 (IRAK1)
  • IRAK1-binding region of PELI1, PELI2, PELI3 proteins consists largely of a previously unidentified forkhead-associated (FHA) domain
  • binds constitutively with IL1R and forms an lL1-induced complex with IRAK4-IRAK1-TRAF6
  • targeting of PELI1 by MIR21 could potentially provide the basis for a negative feedback cycle regulating NF-kappaB signaling
  • (IRAK)-interacting proteins that possess RING-like domains
  • IRF3-dependent gene
  • interacting with IKBKE/TBK1 (IKBKE/TBK1 mediate the activation of PELI1 E3 ligase activity, as well as inducing the transcription of its gene and protein expression in response to TLR3 and TLR4 agonists)
  • directly interacted with the oncoprotein B cell chronic lymphocytic leukemia (BCL6) and induced lysine 63-mediated BCL6 polyubiquitination
  • E3 ubiquitin ligase PELI1 is a negative regulator of IFN1 induction in microglia, innate immune cells of the central nervous system (CNS)
  • ubiquitination of RIPK1 by PELI1 promotes the formation of necrosome and execution of necroptosis
  • cell & other
    REGULATION
    activated by dephosphorylation of multiple sites (required to inactivate Pellino 1, which could be a device for prolonging Pellino's E3 ubiquitin ligase activity)
    IKBKE/TBK1 that mediate the activation of PELI1 E3 ligase activity, as well as inducing the transcription of its gene and protein expression in response to TLR3 and TLR4 agonists
    Other phosphorylated at multiple sites by IRAK1 and IRAK4 and activation can be achieved by phosphorylating any one of several sites or a combination of other sites
    post-translationally modified by small-ubiquitin-related modifier-1 (SUMO1)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    deficiency of Pellino 1 (PELI1), an E3 ubiquitin ligase, blocked necroptosis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularaquiredheart failure
    target for treatment of cardiac fibrosis and heart failure
    ANIMAL & CELL MODELS