Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
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
Location 11q22.3      Physical location : 104.896.245 - 104.972.158
Synonym name
  • caspase 1, apoptosis-related cysteine protease (interleukin 1, beta, convertase)
  • caspase-1
  • interleukin 1-beta convertase
  • Synonym symbol(s) FCE, IL1BC, ICE, P45, IL1BCE, CASP-1
    EC.number 3.4.22.36
    DNA
    TYPE functioning gene
    STRUCTURE 9.62 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    Map cen - (PGR ,D11S35 ,D11S898 ,D11S940 ) - D11S1339 - MMP10 ,MMP1 - D11S1167 ,MMP3 ,MMP13 - D11S611 - D11S2020 - D11S1886 - D11S1302 - CASP1 - D11S2000 - D11S1325 ,GRIA4 - qter
    Physical map
    LOC390248 11 similar to matrix metalloproteinase 1 precursor MMP10 11q22.2-q22.3 matrix metalloproteinase 10 (stromelysin 2) MMP1 11q22.2-q22.3 matrix metalloproteinase 1 (interstitial collagenase) LOC120321 11q22.2 similar to casein kinase 1, alpha 1 MMP3 11q22.2-q22.3 matrix metalloproteinase 3 (stromelysin 1, progelatinase) MMP12 11q22.3 matrix metalloproteinase 12 (macrophage elastase) MMP13 11q22.2-q22.3 matrix metalloproteinase 13 (collagenase 3) MGC2714 11q22.2 hypothetical protein MGC2714 DNCH2 11q21-q22.1 dynein, cytoplasmic, heavy polypeptide 2 SCDGF-B CASP12P1 11q22.3 caspase 12 pseudogene 1 CASP4 11q22.2-q22.3 caspase 4, apoptosis-related cysteine protease CASP5 11q22.2-q22.3 caspase 5, apoptosis-related cysteine protease CASP1 11q22.2-q22.3 caspase 1, apoptosis-related cysteine protease (interleukin 1, beta, convertase) COP  clathrin-ordered protein ICEBERG 11q21-q22 ICEBERG caspase-1 inhibitor OR2AL1P 11q23.3 olfactory receptor, family 2, subfamily AL, member 1 pseudogene GRIA4 11q22.3 glutamate receptor, ionotrophic, AMPA 4 KIAA1826 11q22 KIAA1826 protein KBTBD3 11q22.3 kelch repeat and BTB (POZ) domain containing 3 AASDHPPT 11q22 aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase GUCY1A2 11q21-q22 guanylate cyclase 1, soluble, alpha 2 LOC341230 11q23.1 similar to argininosuccinate synthetase
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 splicing 1364 45.16 404 - 1995 7876192
  • also called CASP1-Alpha
  • a 10 exons variant
  • containing exon 2a (longer than 2b)
  • encoding for the longest product
  • mature peptide leading to p10 and p20 subunits
  • having 6 alpha helices
  • inducing apoptosis
  • 9 splicing 1301 42.76 383 - 1995 7876192
  • also called CASP1-BÍta
  • a 9 exons variant
  • containing exon 2a (longer than 2b)
  • lacking exon 3
  • mature peptide leading to p10 and p20 subunits
  • inducing apoptosis
  • intact CARD domain
  • 9 splicing 1085 34.89 311 - 1995 7876192
  • also called CASP1-Gamma
  • a 9 exons variant
  • containing exon 2b (shorter than 2a)
  • lacking exon 3
  • mature peptide leading to p10 and p20 subunits
  • inducing apoptosis
  • 8 splicing 941 29.69 263 - 1995 7876192
  • also called CASP1-Delta
  • a 8 exons variant
  • containing exon 2b (shorter than 2a)
  • lacking exons 3 & 7
  • mature peptide leading to incomplete p10 and p20 subunits
  • not inducing apoptosis
  • 5 splicing 416 10.29 88 - 1995 7876192
  • also called CASP1-Epsilon
  • a 5 exons variant
  • containing exon 2b (shorter than 2a)
  • lacking exons 3 to 7
  • homolog to p10 subunit
  • not inducing apoptosis
  • - - 1189 - 365 in many tissues 1995 7876192
  • also called CASP1-Zeta
  • lacking the major portion of the CARD domain (helix alpha 1, alpha2, and part of alpha3)
  • alternative splicing of part of exon 2
  • inducing apoptosis
  • 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
  • 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)
  • 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
  • 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