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FLASH GENE
Symbol CASP2 contributors: mct - updated : 19-03-2013
HGNC name caspase 2, apoptosis-related cysteine peptidase
HGNC id 1503
Location 7q34      Physical location : 142.985.401 - 143.004.784
Synonym name
  • caspase 2, apoptosis-related cysteine protease (neural precursor cell expressed, developmentally down-regulated 2)
  • NEDD2 apoptosis regulatory gene
  • caspase 2, apoptosis-related cysteine protease
  • ICH-1 protease
  • Synonym symbol(s) ICH1, NEDD2, CASP-2, ICH-1L, ICH-1L/1S, PPP1R57
    EC.number 3.4.22.55
    DNA
    TYPE functioning gene
    SPECIAL FEATURE
    text an element in 9, containing a decoy 3-acceptor site, inhibiting the inclusion of exon 9
    STRUCTURE 19.38 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    EPHB6 7q33-q35 EphB6 TRPV6 7q33-q34 transient receptor potential cation channel, subfamily V, member 6 TRPV5 7q35 transient receptor potential cation channel, subfamily V, member 5 C7orf34 7q35 chromosome 7 open reading frame 34 KEL 7q33 Kell blood group LOC135924 7q35 similar to Olfactory receptor 9A2 LOC346517 7q35 similar to Olfactory receptor 6V1 sdolf 7q35 olfactory receptor sdolf PIP 7q34 prolactin-induced protein TAS2R39 7q35 taste receptor, type 2, member 39 TAS2R40 7q35 taste receptor, type 2, member 40 LOC51064 7q35 glutathione S-transferase subunit 13 homolog FLJ90586 7q35 hypothetical protein FLJ90586 CASP2 7q34-q35 caspase 2, apoptosis-related cysteine protease (neural precursor cell expressed, developmentally down-regulated 2) LOC346521 7q35 similar to Histidine triad nucleotide-binding protein 1 (Adenosine 5-monophosphoramidase) (Protein kinase C inhibitor 1) (Protein kinase C-interacting protein 1) (PKCI-1) CLCN1 7q35 chloride channel 1, skeletal muscle (Thomsen disease, autosomal dominant) KIAA0773 7q35 chloride channel 1, skeletal muscle (Thomsen disease, autosomal dominant) LOC202775 7q35 hypothetical LOC202775 ZYX 7q34-q35 zyxin EPHA1 7q32-q34 EphA1 TAS2R62P 7q35 taste receptor, type 2, member 62 pseudogene TAS2R60 7q35 taste receptor, type 2, member 60 TAS2R41 7q35 taste receptor, type 2, member 41 LOC392132 7 similar to olfactory receptor MOR257-1 LOC392133 7 similar to seven transmembrane helix receptor LOC392134 7 similar to 60S ribosomal protein L26 LOC392135 7 similar to Multifunctional protein ADE2 FLJ40722 7q35 hypothetical protein FLJ40722
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 4145 50.55 452 ubiquitous 1994 8087842
  • also called variant 1, ICH-1L, CASP2L
  • pro-apoptotic excluding exon 9
  • promotes apoptosis
  • RBM5 enhances the formation of proapoptotic Casp-2L
  • 10 - 3927 12 108 - 1994 8087842
    - - 2650 - 77 - 1994 8087842
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   highly
     thymus   highly
    Respiratoryrespiratory tractlarynx  highly
    cell lineage neural precursor cell
    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 , 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
  • 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