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FLASH GENE
Symbol CASP3 contributors: mct/ - updated : 25-11-2015
HGNC name caspase 3, apoptosis-related cysteine peptidase
HGNC id 1504
Location 4q35.1      Physical location : 185.548.851 - 185.570.629
Synonym name
  • caspase 3, apoptosis-related cysteine protease
  • Yama protein
  • apopain
  • procaspase 3
  • PARP cleavage protease
  • cysteine protease CPP32
  • SREBP cleavage activity 1
  • Synonym symbol(s) CPP32, SCA-1, CPP32B, Yama, apopain
    EC.number 3.4.22.56
    DNA
    TYPE functioning gene
    STRUCTURE 21.78 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D4S1596 - CASP3 - D14S1552 - D4S2349 ,D4S1584 - D4S254 - D4S187 ,D4S130 - D4S163 - qter
    Physical map
    BOMB 4q35.1 BH3-only member B protein CLDN22 4pter-qter claudin 22 LOC391721 4 similar to Claudin-22 LOC389245 4 LOC389245 CARF 4q35.1 LOC389245 LOC389246 4 similar to vesicle-associated soluble NSF attachment protein receptor (v-SN; vesicle-associated soluble NSF attachment protein receptor (v-SNARE; homolog of S. cerevisiae VTI1) LOC389247 4 hypothetical gene supported by BC038563 ING1L 4q35.1 inhibitor of growth family, member 1-like MGC10198 4q35.1 hypothetical protein MGC10198 FLJ12716 4q35.1 FLJ12716 protein DKFZp762K222 4q35.1 hypothetical protein DKFZp762K222 ENPP6 4q35.1 ectonucleotide pyrophosphatase/phosphodiesterase 6 LOC391722 4 similar to myosin:SUBUNIT=regulatory light chain MGC24125 4q35.1 hypothetical protein MGC24125 IRF2 4q35.1 interferon regulatory factor 2 CASP3 4q35 caspase 3, apoptosis-related cysteine protease FLJ33167 4q35.1 hypothetical protein FLJ33167 KLIP1 4q35.1 KSHV latent nuclear antigen interacting protein 1 FACL2 4q34-q35 fatty-acid-Coenzyme A ligase, long-chain 2 LOC285435 4q35.1 hypothetical LOC285435 LOC391723 4 similar to Heslike SLC25A4 4q35 solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 4 KIAA1430 4q35.1 KIAA1430 protein SNX25 4q35.1 sorting nexin 25 DKFZp761O0113 4q35.1 hypothetical protein DKFZp761O0113 Lrp2bp 4q35.1 low density lipoprotein receptor-related protein binding protein FLJ11200 4q35.1 hypothetical protein FLJ11200 MGC33607 4q35.1 hypothetical protein MGC33607 ALP LOC391724 4 similar to glycine-rich protein ARGBP2 4q35.1 similar to glycine-rich protein PRO0618 4q35.1 PRO0618 protein
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 splicing 2689 31.5 277 - 2013 23727203
    variant alpha encoding the same protein than variant beta
    7 splicing 2522 31.5 277 - 2013 23727203
  • variant beta lacking 167nt in the 5' UTR compared to variant alpha
  • encoding the same protein than variant alpha
  • - splicing - - 182 ubiquitous 2013 23727203
    attenuate apoptosis induced by proteasome inhibition
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveesophagus   highly
     liver   highly
    Hearing/Equilibriumearinnercochlea highly
    Lymphoid/Immunelymph node   highly
     spleen   highly
    Nervousbrain   moderately
    Reproductivemale systemtestis  lowly
    Respiratorylung   highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    Muscularstriatumskeletal moderately
    cells
    SystemCellPubmedSpeciesStageRna symbol
    not specificmast cell Homo sapiens
    cell lineage
    cell lines highly in cells of the immune system
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a short prodomain
  • a N terminal (Fas-associating protein with DEATH domain) FADD-like death effector domain and
  • a conserved QACXG pentapeptide active site motif
  • conjugated PhosphoP
    mono polymer heteromer , tetramer
    isoforms Precursor precursor producing two subunits, large (17kDa) and small (12kDa) that dimerize
    HOMOLOGY
    interspecies homolog to rattus Casp3 (89.17 pc)
    homolog to murine Casp3 (86.64 pc)
    Homologene
    FAMILY
  • caspase family of cysteinyl-aspartate specific proteases
  • caspase 3 subfamily
  • peptidase C14A family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text
  • procaspase 3 stored in the mitochondrial intermembrane space and released into cytosol after appropriate apoptotic stimuli
  • active caspase-3 can be stored within secretory compartments of viable mast cells
  • in viable cells, is found as a cytosolic inactive proenzyme and CASP3 activation is largely confined to processes associated with cell death (pMID: 23817418)
  • basic FUNCTION
  • effector caspase in the Fas (TNFRSF6) proapoptotic pathway
  • cleaving and activating CASP6, CASP7, CASP9
  • involved in the activation cascade of caspases responsible for apoptosis execution
  • involved in DNA repair and metabolism of PARP, SREBPs (huntingtin, APP and others)
  • attenuates XIAP (X-linked inhibitor of apoptosis protein)-mediated inhibition of caspase 9
  • predominant caspase involved in the cleavage of amyloid-beta 4A precursor
  • primary effector that executes programmed cell death, and plays an important role in the development and progression of cancer
  • CASP3 was found to be generally more promiscuous than CASP7 and appears to be the major executioner caspase during the demolition phase of apoptosis
  • CASP3 and CASP7 are considered functionally redundant proteases with similar proteolytic specificities
  • CASP3 and CASP7 exhibit differences in protease activity, specific homodimer-forming activity, and three-dimensional structural features, all of which are closely interrelated
  • with SLC30A4, MAP1LC3A and CASP3 might play a role in the pathophysiology of recurrent neonatal seizure-induced acute and long-term brain damage
  • key mediator of neuronal programmed cell death
  • CASP3 activation, a crucial event of neuronal cell death program, is also a feature of many chronic neurodegenerative diseases
  • protects stressed organs against cell death
  • active CASP3 is removed from cells by release of CASP3-enriched vesicles
  • involved in the signalling in erythroid differentiation by targeting late progenitors
  • is a main executioner of apoptotic cell death
  • key mediator of neuronal death in the acute stage of stroke
  • CASP3-dependent mechanism that constrains stroke-induced endogenous neurogenesis and should revitalize interest in targeting CASP3 for treatment of stroke
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • N terminus of the membrane bound form and the cytoplasmic form are different
  • heterotetramer consisting of two heterodimers of p12 and p17 cleaved for the preprotein form
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • cleaving abundant cytoplasmic (i.e gelsolin, fodrin..) and nuclear (lamin, U1 SnRNP-70Kd) proteins kinases
  • binding to and ubiquitinated by BIRC2
  • interacting with DSG2 (apoptotic processing of DSG2 is mediated by caspase 3 in epithelial cells)
  • presynaptic protein ATCAY is a substrate of CASP3 and CASP7
  • PAWR is a novel substrate of CASP3 during apoptosis (the novel specific CASP3 cleavage site in PAWR, and the cleaved fragment of PAWR retains proapoptotic activity)
  • ANP32B is a direct substrate for CASP3 and acted as a negative regulator for leukemic cell apoptosis
  • TRIB3 might prevent cytoplasmic activation of CASP3 by promoting proCASP3 entry into the nucleus, and thereby inhibit apoptosis
  • NUMBL could decrease the expression of TRAF6, CCND1, and MMP9 and increase the expression of CASP3
  • NEK5,is a novel substrate for CASP3, and CASP3 activity, an important factor for myogenic differentiation, was enhanced by NEK5 cleavage
  • after activation by CASP9, CASP3 inhibits ROS production and is required for efficient execution of apoptosis, while effector CASP7 is required for apoptotic cell detachment
  • negatively regulated the proliferation of neuronal precursor cells (NPCs) through reducing the phosphorylation of AKT1
  • MET can directly inhibit CASP3 by way of a novel mechanism and promote hepatocyte survival
  • CASP3, CASP9, and MAPK14 interacted with SLIT1-ROBO2 signaling
  • FANCD2 is a novel and specific substrate of CASP3 (cleavage of FANCD2 by CASP3 did not require either the FA core complex or mono-ubiquitylation of FANCD2, and was stimulated by TP53)
  • CASP3 activation was mediated by serine protease proteinase 3 (PRTN3), which is present in the cytosol of aging neutrophils (PRTN3 cleaved procaspase-3 at a site upstream of the canonical CASP9 cleavage sit
  • MTRNR2L1 protected RPE cells from oxidative stress-induced cell death by STAT3 phosphorylation and inhibiting CASP3 activation
  • cell & other
    REGULATION
    activated by CASP9, CASP8, CASP10
    LPS and rapidly released from HUVEC into the extracellular space. HUVEC escape from cell death and failure of this mechanism may result in endothelial injury/dysfunction
    inhibited by BIRC2, BIRC3,
    BIRC4 (XIAP)
    isatin sulfonamides
    Other inactive form is S-nitrosylated and denitrosylated upon Fas activation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in prostate cancer (in progression)
    tumoral somatic mutation      
    in colon and lung carcinoma
    Susceptibility
  • to lung cancer
  • to Kawasaki disease
  • Variant & Polymorphism other
  • GAGC haplotype carrying the variant allele at all of the -928A > G, 77G > A, and 17532A > C loci was associated with a significantly decreased risk of lung cancer compared to the AGGA haplotype carrying no variant alleles
  • G to A substitution of one commonly associated SNP located in the 5&
  • 8242; untranslated region of CASP3 (rs72689236) increases risk of Kawasaki disease
    Candidate gene
    Marker
    Therapy target
  • mutation V266E activates CASP3 in absence of chain cleavage and is uninhibitable, and thus may lead to novel therapeutic strategies for inducing cell death
  • ANIMAL & CELL MODELS