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FLASH GENE
Symbol NAIP contributors: mct/npt - updated : 01-04-2019
HGNC name NLR family, apoptosis inhibitory protein
HGNC id 7634
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • three N terminal baculovirus IAP repeats (BIR), and the BIR3 domain binds to procaspase-9
  • a C-terminal RING zinc finger domain with two transcripts NAIPL (large), NAIPS (shorter)
  • a NACHT and NAD domain
  • a Leucine Rich Repeat (LRR)
  • a NOD domain, that may interact with NOD containing molecules involved in apoptosis and integrity of this NOD domain is essential for effective inhibition of procaspase-9 and procaspase-3 cleavage by the NAIP protein, and interacts with the NOD domain of APAF1 forming a bridge between procaspase-9 and APAF1
    • HOMOLOGY
    Homologene
    FAMILY
  • baculovirus IAP related family
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    text
  • during metaphase, NAIP accumulates in the mitotic spindle poles and is shown in spindle microtubules
  • in anaphase NAIP is detected in the middle of the central spindle and at the end of cytokinesis, NAIP is localized in the outlying region of the stem body, the center of the intercellular bridge formed between daughter cells prior to cellular abscission
    • basic FUNCTION
  • maybe involved in the expression of SMA
  • regulation of cellular differentiation of neurons (inhibitor of cell death)
  • innate immune recognition of flagellin is shared by transmembrane TLR5 and cytosolic NLRC4/NAIP
  • is not only a true caspase inhibitor, but also showed that unlike XIAP it is unique in inhibiting the cleavage of procaspase-9
  • regulates the apparent specificity of the NLRC4 inflammasome for distinct bacterial ligands
  • NAIP functions to activate the inflammasome in response to flagellin
  • potential new role for NAIP in addition to anti-apoptotic and innate immunology functions
  • in contrast to murine NAIPs, promiscuous recognition of multiple bacterial ligands is conferred by a single human NAIP
  • will have broad implications for ALS symptoms
  • NAIP is abundantly expressed in M2 macrophages, while BIRC2 and BIRC3 show an inverse pattern of expression in polarized macrophages, with elevated expression levels of BIRC2 in M2 and BIRC3 preferentially expressed in M1
    • CELLULAR PROCESS cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • is a constituent of the inflammasome and a key component of the innate immune system 5)
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • flagellin recognition by NAIP stimulates the physical association between NAIP and NLRC4, thereby signalling downstream CASP1 activation
  • regulation of NAIP by TEAD1/YAP1 is at the transcriptional level
  • IRF8 is a critical regulator of NAIP and NLRC4 inflammasome activation for defense against bacterial infection
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) AMCSMA1 , SMA2 , SMA3 , SMA
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • is a risk factor and a promising prognostic biomarker in amyotrophic lateral sclerosis (ALS)
    • Therapy target
    ANIMAL & CELL MODELS