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FLASH GENE
Symbol CASP1 contributors: mct/pgu - updated : 18-09-2016
HGNC name caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase)
HGNC id 1499
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveesophagus   highly
 intestinesmall intestine  highly
 mouthtongue  highly
 pharynx   highly
 salivary gland   highly
 stomach   lowly
Lymphoid/Immunelymph node   lowly
 spleen   highly
Nervousnerve   lowly
Respiratoryrespiratory tractlarynx  lowly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connective   lowly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal (Fas-associating protein with DEATH domain) FADD-like death effector domain
  • one CARD domain containing 6 alpha-helices required for the interactions with the other proteins
  • a conserved QACRG pentapeptide active site motif near the C-terminus
  • secondary structure (p20/p10)2
    mono polymer heteromer , tetramer
    isoforms Precursor mature peptide leading to large (20 kDa) and small (10 kDa) subunits, that dimerize
    HOMOLOGY
    interspecies homolog to rattus Casp1 (63.25 pc)
    homolog to murine Casp1 (62.44 pc)
    Homologene
    FAMILY
  • caspase family of cysteinyl-aspartate specific proteases
  • peptidase C14A family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    text stored in the mitochondrial intermembrane space and released into cytosol after appropriate apoptotic stimuli
    basic FUNCTION
  • interleukin 1, beta-convertase
  • cysteine containing aspartate-specific protease, involved in procytokine activation
  • apical mediator of neuronal cell death during hypoxia/ischemia (after RIPK2 cleavage)
  • CASP1, CASP8, and calpain are dispensable for IL33 release by macrophages
  • cysteine protease responsible for the processing and secretion of IL1B and IL18, which are closely related to the induction of inflammation
  • plays a critical role in the cascade of events involved in the genesis of inflammatory hypernociception by promoting IL1B maturation
  • CASP1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria
  • synthesized as a proprotein, Caspase-1 undergoes autoproteolysis within multiprotein complexes called inflammasomes
  • active caspase-1 increased cellular membrane permeability and intracellular calcium levels, which facilitated lysosome exocytosis and release of host antimicrobial factors and microbial products
  • catalytic activity of caspase-1 is dispensable for necrosis induction
  • fundamental role for NLRP3/CASP1 mediated inflammation in behavioural and cognitive dysfunction in Alzheimer disease
  • in the presence of CASP1, CASP8 acts as a positive modulator of the NLRP3-dependent CASP1 signaling cascades that drive both IL1B production and pyroptotic death
  • CASP4 is upstream of CASP1 in the pathway that regulates pyroptosis and IL1B synthesis in macrophages during DENV-2 infection
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    text effector of apoptosis
    PATHWAY
    metabolism
    signaling
  • inflammasome pathway, including NLRP6, PYCARD, CASP1, and IL18
  • two conserved secretion pathways are initiated by caspase-1, lysosome exocytosis, and a parallel pathway resulting in cytokine release, and both enhance the antimicrobial nature of pyroptosis
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • activating interleukin 1 beta
  • mediator of RIPK2 cleavage in hypoxia/ischemia -stimulated neurons
  • physically interacted with full length RARRES3 (enzymatic activity of caspase-1 was necessary to control RARRES3, although it was not a substrate of proteolytic cleavage by caspase-1)
  • interacting with PANX1
  • AIM2 is a new receptor for cytoplasmic DNA, which forms an inflammasome with the ligand and PYCARD to activate CASP1
  • interaction with TIRAP (inhibitory, rather than an activating role for CASP1 in TIRAP regulation, and the caspase-1 cleavage site in TIRAP is part of a TIR-domain interaction site)
  • interacting with PYCARD, AIM2 and NLRP3 (PYCARD inflammasomes, including AIM2 and NLRP3, are critical for CASP1 activation induced by S. pneumoniae)
  • important role of CASP4 in inflammation and innate immunity through activation of CASP1
  • NLRP3 is a key component of one of several distinct cytoplasmic multiprotein complexes (inflammasomes) that mediate the maturation of the proinflammatory cytokine IL1B by activating CASP1
  • LRRFIP2 enhances the interaction between FLII and CASP1, facilitating the inhibitory effect of FLII on CASP1 activation
  • PLIN2 inhibits insulin&
  • 8209;induced glucose uptake by activating NLRP3, CASP1 and IL1B, leading to a decreased IRS1 expression
  • RAB39A binds CASP1 and is required for CASP1-dependent interleukin-1beta secretion
  • CASP1, controls pyroptosis- and ubiquitin-independent proteasomal degradation of UBE2L3 upon canonical and non-canonical inflammasome activation by sterile danger signals and bacterial infection
  • epigenetic regulation of NOS2 by CASP1 involves cleavage of the chromatin regulator PARP1 and chromatin accessibility of the NFKB1 binding sites located at the NOS2 promoter
  • endogenous NLRC3 interacts with both PYCARD and pro-caspase-1 but not with NLRP3, disrupts PYCARD speck formation through its CARD, and impairs the PYCARD and pro-caspase-1 interaction
  • CASP4 physically interacts with CASP1 and is believed to be a proinflammatory caspase that can induce the inflammatory form of programmed cell death (pyroptosis) and the release of mature interleukin IL1B
  • cell & other
    REGULATION
    activated by processed CASP8
    Other BCL2 and BCL2L1 regulate CASP1 activation by interaction with NALP1
    activation of the cysteine protease Caspase-1 is a key event in the innate immune response to infections
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    in primary prostate cancer (in progression)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneouspain 
    is a key target to control inflammatory pain
    ANIMAL & CELL MODELS
  • caspase-1-deficient mice demonstrate increased colonic epithelial cell proliferation in early stages of injury-induced tumor formation and reduced apoptosis in advanced tumors