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FLASH GENE
Symbol NLRC4 contributors: mct - updated : 04-04-2018
HGNC name NLR family, CARD domain containing 4
HGNC id 16412
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinelarge intestinecolon  
 salivary gland   highly
Endocrineadrenal gland   moderately
Lymphoid/Immunespleen   moderately Homo sapiens
Nervousbrain    
Reproductivemale systemprostate   
Respiratorylung    
Urinarybladder   moderately
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoieticbone marrow   
Connectivebone   
Lymphoid    
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticleukocyte
Blood/Hematopoieticmonocyte
cell lineage
cell lines monocyte cells lines
fluid/secretion blood
at STAGE
physiological period fetal, pregnancy
Text placenta, liver
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal CARD domain
  • a leucine rich repeat (LRR) repeat
  • a NACHT domain
  • 13 leucine rich repeat at the C terminus (LRR)
  • SAM domain
  • HOMOLOGY
    interspecies ortholog to rattus Card12
    ortholog to murine Card12
    intraspecies homolog to APAF1
    Homologene
    FAMILY
  • CED4 family
  • NOD-like receptor family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,intermed filament
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • playing a regulatory role in the processes of inflammation and cell death stimuli
  • involved in activation of CASP1 in response to proinflammatory and apoptotic stimuli
  • activator of caspase 1 in TP53-dependent apoptosis
  • playing a role in the promotion of apoptosis
  • maybe involved in sensing more than one bacterial molecule and may participate in several immune complexes
  • potential role for ubiquitination of NLRC4 that is enabled by its interaction with PSMC5, leading to caspase 8 activation and cell death
  • activates caspase 1 in response to bacterial virulence factors including type III and IV secretion systems (T3SS and T4SS)
  • redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella
  • innate immune recognition of flagellin is shared by transmembrane TLR5 and cytosolic NLRC4/NAIP
  • activates CASP1 and downstream inflammatory response upon sensing cytosolic presence of flagellin during bacterial infection
  • acts as an adaptor through which inflammasome activation signals generated from different NAIP receptors are transduced to CASP1
  • intracellular receptors, such as NLRP1, NLRP3, NLRP6 and NLRC4, which mediate the assembly of inflammasome complexes leading to the activation of procaspase-1
  • is a cytosolic NOD (nucleotide binding and oligomerization domain)-like receptor (NLR) that can trigger inflammasome formation in response to bacterial flagellin, an immunodominant antigen in the intestine
  • importance of NLRC4 not only in the innate immune response to bacterial infections but also in the genesis of inflammatory diseases
  • NLRC4-driven IL1B production is critical for the progression of Diabetic Nephropathy
  • NLRC4 and NLRP3, which normally form distinct inflammasomes, activate an lysophosphatidylcholine (LPC)-induced inflammasome and are important in astrogliosis and microgliosis
  • NLRC4 stimulation leads to CASP1 activation followed by a rapid lytic cell death known as pyroptosis
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • activating procaspase 1
  • NFKB regulators (BCL10, CARD15)
  • PYCARD
  • Nod2
  • NALP1 (NAC)
  • PSMC5 binds to AAs 91-253 of NLRC4, which is also the region that the LRR domain binds to, potentiating cell death induced by NLRC4 and LRR-domain-deleted NLRC4, and co-expression of PSMC5 and NLRC4 induces CASP8-dependent cell death
  • interacting with NAIP (NAIP regulates the apparent specificity of the NLRC4 inflammasome for distinct bacterial ligands)
  • PYCARD connects pathogen/danger sensors such as NLRP3 and NLRC4 with caspases and is involved in inflammation and cell death
  • flagellin recognition by NAIP stimulates the physical association between NAIP and NLRC4, thereby signalling downstream CASP1 activation
  • ARRB1 plays a critical role in the assembly and activation of two major canonical inflammasomes, NLRC4, NLRP3
  • activation of NLRC4 by bacterial flagellin downregulated the flagellin-induced and TLR5-mediated immune responses against flagellin
  • NLRC4 interacts with PSMC5 and induces CASP8-mediated cell death
  • IRF8 is required for optimal activation of the NLRC4 inflammasome in bone-marrow-derived macrophages infected with Salmonella Typhimurium
  • IRF8 is a critical regulator of NLR family apoptosis inhibitory proteins (NAIPs) and NLRC4 inflammasome activation for defense against bacterial infection
  • cell & other
    REGULATION
    Other is activated as part of the innate immune response to a range of intracellular bacteria, including S. typhimurium and Legionella pneumophila
    ASSOCIATED DISORDERS
    corresponding disease(s) FCAS4 , AIFEC
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    mRNA levels of NLRC4, NLRP12, and IL1B were significantly upregulated in Kawasaki disease (KD) patients compared to the controls
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyacquired 
    NLRC4 and AIM2 inflammasomes are potential therapeutic targets for stroke and provide new insights into how the inflammatory response is regulated after an acute injury to the brain
    ANIMAL & CELL MODELS
  • transgenic mice that expressed mutant Nlrc4 under the invariant chain promoter developed dermatitis and arthritis