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FLASH GENE
Symbol CASP2 contributors: mct - updated : 19-03-2015
HGNC name caspase 2, apoptosis-related cysteine peptidase
HGNC id 1503
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 , tetramer
    isoforms Precursor precursor producing two subunits,large (18kDa) and small (12kDa),that dimerize
    HOMOLOGY
    interspecies ortholog to murine Nedd 2
    intraspecies paralog to CASP1
    Homologene
    FAMILY
  • caspase family of cysteinyl-aspartate specific proteases
  • peptidase C14 family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • procaspase 2 stored in the mitochondrial intermembrane space and released into cytosol after appropriate apoptotic stimuli
  • has a unique ability to localize to the nucleus
  • basic FUNCTION
  • cysteine containing aspartate-specific protease, mammalian interleukin 1 beta convertase, promoting apoptosis
  • splicing regulation of CASP-2L/CASP-2S may play an important role in neural development
  • required in stress induced apoptosis for permeabilization of mitochondria
  • potent inducer of NF-kappaB and p38 MAPK activation in a TRAF2-mediated way
  • required for apoptosis induced by cytoskeletal disruption, having a context-dependent function
  • role of caspase-2 as a tumor suppressor appears to be unique among mammalian caspases
  • functions as an endogenous inhibitor of NFkappaB-dependent cell survival and this mechanism may contribute to tumor suppression
  • changes of CASP2 and CASP5 activities could be indicative of their involvement in the cervical malignancy mechanisms
  • its expression promotes growth arrest and chemotherapy resistance by a mechanism that depends on CASP2 and wild-type TP53
  • initiator caspase, which has been implicated to function in apoptotic and non-apoptotic signalling pathways, including cell-cycle regulation, DNA-damage signalling and tumour suppression
  • neuronally expressed developmentally down-regulated gene required for neuronal death induced by several stimuli, including NGF (nerve growth factor) deprivation and APP (
  • highly conserved CASP2 is required for pore-forming toxins (PFT)-mediated apoptosis
  • obligatory role as an initiator caspase during PFT-mediated apoptosis
  • CELLULAR PROCESS cell life, cell death/apoptosis
    cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS
    text apoptotic or antiapoptotic depending upon cell lineage and stage of development
    PATHWAY
    metabolism
    signaling
    a component
  • complex with TRAF2, and RALBP1 that activates NF-kappaB and p38 MAPK through the caspase recruitment domain of caspase-2 independently of its proteolytic activity
  • PIDDosome, which is an oligomeric signaling complex composed of PIDD1, CRADD and CASP2, can induce proximity-based dimerization and activation of CASP2
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with NALP1
  • interacts with TRAF1, TRAF2, and RALBP1
  • MDM2 is a cleavage target of Caspase-2 and provide insight into a mechanism of Mdm2 inhibition that impacts TP53 dynamics upon genotoxic stress
  • cell & other
    REGULATION
    activated by the TP53 target gene product PIDD (also known as LRDD) in a complex called the Caspase-2-PIDDosome
    repressed by RAS (RAS-induced down-regulation of CASP2 represents a novel mechanism by which oncogenic RAS protects malignant intestinal epithelial cells from anoikis, promotes their anchorage-independent growth, and allows them to form tumors)
    Other developmentally downregulated
    rgulated by RBM5 (CASP2 splicing regulation by RBM5 may contribute to its tumor suppressor activity)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    results in an increased ability of cells to acquire a transformed phenotype and become malignant, indicating that it is a tumor suppressor
    constitutional       loss of function
    promotes aberrant DNA-damage response and genetic instability, leading to defective TP53-mediated signalling and decreased trans-activation of TP53 target genes upon DNA damage
    constitutional       loss of function
    may play a role in promoting marrow adiposity under stress or disease conditions, but it is not required for T1-diabetes induced bone loss
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    caspase-2(-/-) mouse embryonic fibroblasts (MEFs) show increased proliferation