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FLASH GENE
Symbol LRRFIP2 contributors: mct - updated : 29-03-2023
HGNC name leucine rich repeat (in FLII) interacting protein 2
HGNC id 6703
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • coiled motifs interacting with the LRR domain of FLI
  • HOMOLOGY
    Homologene
    FAMILY
  • LRRFIP family
  • CATEGORY unknown/unspecified
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    text
  • by promoting the translocation of LRRFIP2 into cytoplasmic aggregates, UBD might block its recruitment to the membrane and its subsequent role in NFKB1 activation through TLR4 stimulation
  • basic FUNCTION
  • plays an important role in transducing Wnt signals
  • positively regulate cytokine production in macrophages, suggesting a functional role in TLR4-mediated inflammatory response
  • positively regulates NFKB and macrophage cytokine production after lipopolysaccharide
  • signal regulator, that modulates the time course-dependent changes in NFKB activity through its dynamic interaction with the TLR adaptor protein, MYD88
  • FLII and LRRFIP2 repress caspase-1 activation, which could be restored through the severing of actin filaments in a Ca2+-dependent process
  • both LRRFIP2 and FLII control the localization of NLRP3 with F-actin as well as the activity of NLRP3 inflammasome
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • FLI binding
  • interacts with DVL3 to increase the cellular levels of beta-catenin and activate beta-catenin/LEF/TCF-dependent transcriptional activity
  • MYD88 interacting with LRRFIP2 and LRRFIP1, and both are positive regulators of NF-kappaB activity
  • binds to MYD88 through its serine-rich domain (phosphorylation at serine 202 was found to regulate the dynamics of the LRRFIP2-MYD88 interaction, which in turn modulated the strength and duration of TLR4 signaling)
  • LRRFIP2 is involved in NFKB1 activation following stimulation of TLR4
  • LRRFIP2 and TOR1AIP2 are FATylation substrates
  • LRRFIP2 enhances the interaction between FLII and CASP1, facilitating the inhibitory effect of FLII on CASP1 activation
  • FLII is recruited to the NLRP3 inflammasome by leucine-rich repeat FliI-interaction protein 2 (LRRFIP2), an NLRP3-associated protein
  • LRRFIP2 and FLII is required for the co-localization of the NLRP3 and F-actin as well as for the inhibition of NLRP3 inflammasome activity
  • LRRFIP2 is regulated by epithelial splicing regulatory protein 1 (ESRP1) and this is correlated with metastatic potential of gastric cancer cells
  • epithelial LRRFIP2 isoform (variant 2) inhibited the oncogenic function of coactivator-associated arginine methyltransferase 1 (CARM1) through interaction
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    deletion, comprising exons 17-19 of the MLH1 gene and exons 26-29 of the LRRFIP2 gene in Lynch syndrome
    tumoral fusion      
    LRRFIP2-RAF1 fusion identified in an acral melanoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS