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FLASH GENE
Symbol CASP4 contributors: shn/npt/pgu - updated : 02-06-2013
HGNC name caspase 4, apoptosis-related cysteine peptidase
HGNC id 1505
Location 11q22.3      Physical location : 104.813.593 - 104.839.325
Synonym name
  • apoptotic cysteine protease Mih1/TX
  • caspase 4, apoptosis-related cysteine protease
  • ICH-2 protease
  • caspase-4
  • protease ICH-2
  • protease TX
  • caspase 11
  • Synonym symbol(s) TX, ICH-2, Mih1/TX, ICEREL-II, ICE(rel)II, ICE(rel)-II, CASP-4
    EC.number 3.4.22.57, 3.4.22.36
    DNA
    TYPE functioning gene
    STRUCTURE 25.73 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure colocalizes with a cluster of functionally related genes CASP1, 5 and 12 and CASP1 pseudo genes ICE-BERG, COP and INCA
    MAPPING cloned Y linked N status provisional
    Map cen - D11S4951 - D11S1886 - CASP4 - D11S1781 - D11S2017 - 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
    9 splicing 1352 - 321 - 1999 9931493
  • transcript variant gamma
  • 9 splicing 1319 - 377 - 1999 9931493
  • transcript variant alpha
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   lowly
    Digestiveintestinelarge intestinecolon lowly
     intestinesmall intestine  highly
     liver   moderately
    Endocrinepancreas   lowly
    Lymphoid/Immunespleen   highly
     thymus   lowly
    Reproductivefemale systemovary  highly
     female systemplacenta  highly
     male systemprostate  lowly
     male systemtestis  lowly
    Respiratorylung   moderately
    Urinarykidney   lowly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    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
  • a conserved QACXG pentapeptide active site motif
  • mono polymer heteromer , dimer
    isoforms Precursor precursor producing two subunits,large and small,that dimerize
    HOMOLOGY
    interspecies homolog to mammalian interleukin 1 beta convertase (IL1BC)
    ortholog to Casp4, Mus musculus
    ortholog to Casp4, Rattus norvegicus
    ortholog to CASP4, Pan troglodytes
    Homologene
    FAMILY
  • cysteine-aspartic acid protease (caspase) family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • stored in the mitochondrial intermembrane space and released into cytosol after appropriate apoptotic stimuli
  • ocalized to the ER membrane
  • basic FUNCTION
  • involved in Fas-mediated apoptosis
  • cysteine containing aspartate-specific protease, potentially involved in procytokine activation
  • promoting apoptosis
  • a key mediator of apoptosis and inflammation in human retinal pigment epithelial cells
  • required for non-canonical inflammasome-triggered macrophage cell death, indicating that caspase-11 (CASP4) orchestrates both caspase-1-dependent and -independent outputs
  • a unique pro-inflammatory role for caspase-11 in the innate immune response to clinically significant bacterial infections
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS inflammation
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
  • direct interaction of APBB1 and TSHZ3 with the promoter region of CASP4
  • RNA
    small molecule
    protein
  • cleaving and activating CASP1
  • NALP1
  • Caspase-14, CASP14 (Hu et al, 1998)
  • TNF receptor-associated factor 6, TRAF6
  • cell & other
    REGULATION
    inhibited by inhibitor 9, PI9
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • knock-down of CASP4 by siRNA reduces NF-kappaB activation and nuclear translocation
  • Casp11(-/-) mice, exhibited defects in IL-1&
  • 946; production and harboured a mutation in the Casp11 locus that attenuated caspase-11 expression
  • loss of caspase-11 rather than caspase-1 protected mice from a lethal dose of lipopolysaccharide