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CASP3 caspase 3, apoptosis-related cysteine peptidase [ Homo sapiens (human) ]

Gene ID: 836, updated on 29-Sep-2014
Official Symbol
CASP3provided by HGNC
Official Full Name
caspase 3, apoptosis-related cysteine peptidaseprovided by HGNC
Primary source
HGNC:HGNC:1504
See related
Ensembl:ENSG00000164305; HPRD:02799; MIM:600636; Vega:OTTHUMG00000133681
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CPP32; SCA-1; CPP32B
Summary
This gene encodes a protein which is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 6, 7 and 9, and the protein itself is processed by caspases 8, 9 and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. Alternative splicing of this gene results in two transcript variants that encode the same protein. [provided by RefSeq, Jul 2008]
See CASP3 in Epigenomics, MapViewer
Location:
4q34
Exon count:
8
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 4 NC_000004.12 (184627696..184649475, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (185548850..185570629, complement)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC102723779 Neighboring gene GAR1 ribonucleoprotein homolog (yeast) pseudogene Neighboring gene primase and polymerase (DNA-directed) Neighboring gene centromere protein U Neighboring gene acyl-CoA synthetase long-chain family member 1 Neighboring gene proteoglycan 3 pseudogene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120/41 Envelope proteins form a complex with integrin alpha4beta7 and chemokine receptor CCR5 on the CD4-negative gamma-delta T cell membrane, which leads to activation of the p38-caspase pathway and induces the death of gamma-delta cells PubMed
env HIV-1 R5-tropic Env-mediated apoptosis of bystander cells is dependent on both CCR5 expression levels and fusogenic activity of the Env glycoprotein through the mechanism of apoptosis involved caspase-3 activation and mitochondrial depolarization PubMed
env Treatment of HIV-1 Env-pseudotyped virus-infected MDM cells with both soluble TRAIL and an agonistic anti-DR5 antibody AD5-10 induces activation of caspase-3, -8, and -9 PubMed
env HIV-1 gp120-mediated activation of caspase 8 occurs in a p53 independent manner, while HIV-1 gp120-mediated activation of caspase 3 requires p53 PubMed
env Siva-1 sensitizes CD4-positive T-cells to HIV-1 gp120/gp41-induced apoptosis. The Siva-1-mediated sensitization on CD4-positive T-cells shows significant activation of caspase-3, -8, and -9 PubMed
env Inactivation of PKR has an inhibitory effect on gp120-induced caspase-3 activation PubMed
env Gp120-mediated activation of caspase-3 is significantly reduced in cells pretreated with PDGF-B PubMed
env The combinatorial toxicity of cocaine and gp120 is accompanied by an increase in both caspase-3 activity and expression of the proapoptotic protein Bax in HIV-associated neuropathological disorders PubMed
env The cytolytic process that takes place between primary uninfected CD4+ T cells and HIV-1 infected or HIV-1 gp120-expressing cells requires the activity of caspases such as ICE and CPP32 PubMed
env The interaction of cell-associated HIV-1 gp120 with CXCR4-expressing target cells triggers apoptotic processes by activating caspase-9 and -3 PubMed
env Induction of apoptosis in cell cultures through binding of HIV-1 gp120 or gp160 to CXCR4 involves protein kinase C, basic fibroblast growth factor, caspase-3, and the pro-apoptotic molecule Bax PubMed
env Signal transducer and activator of transcription factor 1 (STAT1) partially regulates HIV-1 gp120/HCV E2-induced caspase 3 activity PubMed
Envelope transmembrane glycoprotein gp41 env HIV-1 gp120/41 Envelope proteins form a complex with integrin alpha4beta7 and chemokine receptor CCR5 on the CD4-negative gamma-delta T cell membrane, which leads to activation of the p38-caspase pathway and induces the death of gamma-delta cells PubMed
env HIV-1 gp41-dependent apoptosis involves caspase-3-dependent mitochondrial depolarization and reactive oxygen species production; HIV-1 gp41-induced mitochondrial depolarization is inhibited by the protease inhibitor nelfinavir PubMed
env HIV-1 R5-tropic Env-mediated apoptosis of bystander cells is dependent on both CCR5 expression levels and fusogenic activity of the Env glycoprotein through the mechanism of apoptosis involved caspase-3 activation and mitochondrial depolarization PubMed
env Siva-1 sensitizes CD4-positive T-cells to HIV-1 gp120/gp41-induced apoptosis. The Siva-1-mediated sensitization on CD4-positive T-cells shows significant activation of caspase-3, -8, and -9 PubMed
env A point mutation (V38E) in the gp41 region of HIV-1 abolishes HIV-1-mediated apoptosis by CASP3 and minimizes CD4 loss in humanized mice without altering viral replication PubMed
Nef nef Stable expression of HIV-1 Nef in CEM T cells activates caspase-3 and enhances apoptosis through mechanisms unrelated to Fas PubMed
nef Stable expression of HIV-1 Nef in Jurkat T cells confers resistance to Fas-mediated apoptosis through inactivation of caspase-3 and caspase-8 PubMed
nef Microarray and Western blot analyses have shown HIV-1 Nef-induced apoptosis in human brain micro vascular endothelial cells requires the involvement of caspase-3 and caspase-9 PubMed
Tat tat FasL-induced activation of caspase-3 and -8 proteins is inhibited in HIV-1 Tat101-expressing Jurkat cells PubMed
tat HIV-1 Tat induces apoptosis through activation of caspase-3 PubMed
tat The levels of caspase-3 protein are reduced after Caco-2 cells exposure to HIV-1 Tat compared with control PubMed
tat PDGF-BB prevents caspase-3 activation induced by HIV-1 Tat and morphine in neuroblastoma cells PubMed
tat Tat-triggered PKCdelta and PKCtheta activation results in the downstream signaling through the apoptosis pathways mediated by both ERK1/2 and caspase-3 PubMed
tat Co-administration of morphine and HIV-1 Tat significantly increases the percentage of neurons expressing active caspase-3 PubMed
tat HIV-1 Tat-induced apoptosis through increased expression of anti-apoptotic protein Bcl-2, proapoptotic protein Bax and activation of caspases CASP3 and CASP9 is inhibited by estrogen receptor beta (ER)-mediated estrogen treatment PubMed
tat A p53 fusion protein with the HIV-1 Tat basic domain at its N terminus activates the expression of p21and downregulates the levels of caspase-3 and Bcl-2 PubMed
Vpr vpr Induction of G2 cell cycle arrest by Vpr is upregulated under caspase 3-inhibition and induction of apoptosis by Vpr is downregulated by caspase 3-inhibition PubMed
vpr Inhibition of caspase 3 by compound Z-DEVD-fmk causes accumulation of HIV-1 Vpr at the nuclear envelope. VprL23F and VprP35A mutants abrogate the sensitivity to caspase 3-inhibition PubMed
vpr HIV-1 Vpr increases the activity of caspase-3 and caspase-9, but not of caspase-8 in human HeLa cells; Vpr-induced apoptosis can be inhibited by inhibitors of caspase-3 and caspase-9, but not by inhibitors of caspase-8 PubMed
vpr HIV-1 Vpr-induced apoptosis results in caspase 3 cleavage PubMed
vpr HIV-1 Vpr segments with mutation at the positions 70, 85, 86, or 94 show lower apoptosis-inducing capabilities by the attenuation of Caspase-3 activity PubMed
vpr Virion-associated Vpr activates caspase 3/7, 8, and 9 in Fas-mediated apoptosis in Jurkat T cells and human activated PBMCs PubMed
vpr Virion-associated Vpr triggers apoptosis through caspases 3/7 and 9 in human T cells independently of other HIV de novo-expressed proteins and also activates caspase 8, the initiator caspase of the death receptor pathway PubMed
vpr HIV-1 Vpr-induced apoptosis through caspase activation and Smac release from mitochondria is dependent on G2 cell cycle arrest , but is lost in cells synchronized in G1/S PubMed
vpr Overproduction of EEF2 blocks HIV-1 Vpr-induced cell death both in fission yeast and human cells, suppresses caspase 9 and caspase 3-mediated apoptosis induced by Vpr, and reduces cytochrome c release induced by Vpr PubMed
vpr Through activation of the caspase 9 pathway, HIV-1 Vpr also activates caspase 3 PubMed
Vpu vpu Levels of active caspase-3 are elevated in T cells as a result of HIV-1 Vpu-mediated inhibition of NF-kappa B activation PubMed
retropepsin gag-pol HIV-1 PR cleaves CASP3 to result in three processed products, Myr-lyn signal peptide, p17 and p12 proteins PubMed
gag-pol HIV-1 protease directly cleaves and activates procaspase 8 in T cells which is associated with cleavage of BID, mitochondrial release of cytochrome c, activation of the downstream caspases 9 and 3, and cleavage of DFF and PARP PubMed

Go to the HIV-1, Human Interaction Database

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    SMAC-mediated apoptotic response, organism-specific biosystemOnce released from the mitochondria, SMAC binds to IAP family proteins displacing them from Caspase:IAP complexes liberating the active caspases.
  • SMAC-mediated dissociation of IAP:caspase complexes, organism-specific biosystem (from REACTOME)
    SMAC-mediated dissociation of IAP:caspase complexes, organism-specific biosystemSmac/DIABLO regulates IAP function. Residues 56-59 of Smac/DIABLO are homologous to the amino-terminal motif that is used by caspase-9 to bind to the BIR3 domain of XIAP. Binding of Smac/DIABLO to ...
  • Serotonergic synapse, organism-specific biosystem (from KEGG)
    Serotonergic synapse, organism-specific biosystemSerotonin (5-Hydroxytryptamine, 5-HT) is a monoamine neurotransmitter that plays important roles in physiological functions such as learning and memory, emotion, sleep, pain, motor function and endoc...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by Hippo, organism-specific biosystem (from REACTOME)
    Signaling by Hippo, organism-specific biosystemHuman Hippo signaling is a network of reactions that regulates cell proliferation and apoptosis, centered on a three-step kinase cascade. The cascade was discovered by analysis of Drosophila mutation...
  • Signalling by NGF, organism-specific biosystem (from REACTOME)
    Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
  • Spinal Cord Injury, organism-specific biosystem (from WikiPathways)
    Spinal Cord Injury, organism-specific biosystemThis pathway provides an overview of cell types, therapeutic targets, drugs, new proposed targets and pathways implicated in spinal cord injury. Spinal cord injury is a complex multistep process that...
  • Stimulation of the cell death response by PAK-2p34, organism-specific biosystem (from REACTOME)
    Stimulation of the cell death response by PAK-2p34, organism-specific biosystemIn response to stress signals, the p21-activated protein kinase PAK-2 stimulates a cell death response characterized by increased cell rounding and apoptotic chromatin condensation (see Jakobi et al...
  • Syndecan-2-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    Syndecan-2-mediated signaling events, organism-specific biosystem
    Syndecan-2-mediated signaling events
  • TNF signaling pathway, organism-specific biosystem (from KEGG)
    TNF signaling pathway, organism-specific biosystemTumor necrosis factor (TNF), as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. Activated TNF...
  • TNF signaling pathway, conserved biosystem (from KEGG)
    TNF signaling pathway, conserved biosystemTumor necrosis factor (TNF), as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. Activated TNF...
  • TNF-alpha/NF-kB Signaling Pathway, organism-specific biosystem (from WikiPathways)
    TNF-alpha/NF-kB Signaling Pathway, organism-specific biosystem"The Tumor Necrosis Factor alpha is a proinflammatory cytokine belonging to the TNF superfamily. It signals through 2 separate receptors - TNFRSF1A and TNFRSF1B, both members of the TNF receptor supe...
  • TWEAK Signaling Pathway, organism-specific biosystem (from WikiPathways)
    TWEAK Signaling Pathway, organism-specific biosystemTNF related weak inducer of apoptosis (TWEAK) is a small pleiotropic cytokine of the TNF super family and its gene is located at chromosome 17p13.1. TWEAK has been reported to be expressed in tissues...
  • Toxoplasmosis, organism-specific biosystem (from KEGG)
    Toxoplasmosis, organism-specific biosystemToxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechan...
  • Toxoplasmosis, conserved biosystem (from KEGG)
    Toxoplasmosis, conserved biosystemToxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechan...
  • Tuberculosis, organism-specific biosystem (from KEGG)
    Tuberculosis, organism-specific biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
  • Tuberculosis, conserved biosystem (from KEGG)
    Tuberculosis, conserved biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
  • Viral carcinogenesis, organism-specific biosystem (from KEGG)
    Viral carcinogenesis, organism-specific biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...
  • Viral carcinogenesis, conserved biosystem (from KEGG)
    Viral carcinogenesis, conserved biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...
  • Viral myocarditis, organism-specific biosystem (from KEGG)
    Viral myocarditis, organism-specific biosystemMyocarditis is a cardiac disease associated with inflammation and injury of the myocardium. It results from various etiologies, both noninfectious and infectious, but coxsackievirus B3 (CVB3) is stil...
  • p53 signaling pathway, organism-specific biosystem (from KEGG)
    p53 signaling pathway, organism-specific biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...
  • p53 signaling pathway, conserved biosystem (from KEGG)
    p53 signaling pathway, conserved biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...
  • p75 NTR receptor-mediated signalling, organism-specific biosystem (from REACTOME)
    p75 NTR receptor-mediated signalling, organism-specific biosystemBesides signalling through the tyrosine kinase receptors TRK A, B, and C, the mature neurotrophins NGF, BDNF, and NT3/4 signal through their common receptor p75NTR. NGF binding to p75NTR activates a ...
  • p75(NTR)-mediated signaling, organism-specific biosystem (from Pathway Interaction Database)
    p75(NTR)-mediated signaling, organism-specific biosystem
    p75(NTR)-mediated signaling
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Process Evidence Code Pubs
B cell homeostasis IEA
Inferred from Electronic Annotation
more info
 
T cell homeostasis IEA
Inferred from Electronic Annotation
more info
 
activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c TAS
Traceable Author Statement
more info
 
apoptotic DNA fragmentation TAS
Traceable Author Statement
more info
 
apoptotic process TAS
Traceable Author Statement
more info
 
apoptotic signaling pathway TAS
Traceable Author Statement
more info
PubMed 
cell fate commitment IEA
Inferred from Electronic Annotation
more info
 
cellular component disassembly involved in execution phase of apoptosis TAS
Traceable Author Statement
more info
 
cellular response to DNA damage stimulus IEA
Inferred from Electronic Annotation
more info
 
erythrocyte differentiation IDA
Inferred from Direct Assay
more info
PubMed 
erythrocyte differentiation TAS
Traceable Author Statement
more info
PubMed 
execution phase of apoptosis IDA
Inferred from Direct Assay
more info
PubMed 
execution phase of apoptosis IMP
Inferred from Mutant Phenotype
more info
PubMed 
extracellular matrix disassembly TAS
Traceable Author Statement
more info
 
extracellular matrix organization TAS
Traceable Author Statement
more info
 
extrinsic apoptotic signaling pathway in absence of ligand IEA
Inferred from Electronic Annotation
more info
 
extrinsic apoptotic signaling pathway via death domain receptors IEA
Inferred from Electronic Annotation
more info
 
glial cell apoptotic process IEA
Inferred from Electronic Annotation
more info
 
heart development IEA
Inferred from Electronic Annotation
more info
 
hippo signaling TAS
Traceable Author Statement
more info
 
intrinsic apoptotic signaling pathway TAS
Traceable Author Statement
more info
 
intrinsic apoptotic signaling pathway in response to oxidative stress IEA
Inferred from Electronic Annotation
more info
 
keratinocyte differentiation IBA
Inferred from Biological aspect of Ancestor
more info
 
negative regulation of B cell proliferation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of activated T cell proliferation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of apoptotic process IGI
Inferred from Genetic Interaction
more info
PubMed 
negative regulation of cyclin-dependent protein serine/threonine kinase activity IEA
Inferred from Electronic Annotation
more info
 
neuron apoptotic process IEA
Inferred from Electronic Annotation
more info
 
neuron differentiation IBA
Inferred from Biological aspect of Ancestor
more info
 
neurotrophin TRK receptor signaling pathway TAS
Traceable Author Statement
more info
 
platelet formation TAS
Traceable Author Statement
more info
PubMed 
positive regulation of apoptotic process TAS
Traceable Author Statement
more info
 
positive regulation of neuron apoptotic process IEA
Inferred from Electronic Annotation
more info
 
proteolysis IDA
Inferred from Direct Assay
more info
PubMed 
regulation of apoptotic DNA fragmentation IEA
Inferred from Electronic Annotation
more info
 
regulation of apoptotic process TAS
Traceable Author Statement
more info
 
regulation of cysteine-type endopeptidase activity involved in apoptotic process TAS
Traceable Author Statement
more info
 
release of cytochrome c from mitochondria IEA
Inferred from Electronic Annotation
more info
 
response to UV IEA
Inferred from Electronic Annotation
more info
 
response to tumor necrosis factor TAS
Traceable Author Statement
more info
PubMed 
response to wounding IEA
Inferred from Electronic Annotation
more info
 
sensory perception of sound IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytosol IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
Preferred Names
caspase-3
Names
caspase-3
CASP-3
CPP-32
apopain
procaspase3
protein Yama
PARP cleavage protease
cysteine protease CPP32
SREBP cleavage activity 1
caspase 3, apoptosis-related cysteine protease
NP_004337.2
NP_116786.1

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_004346.3NP_004337.2  caspase-3 preproprotein

    See proteins identical to NP_004337.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (alpha) represents the longer transcript.
    Source sequence(s)
    AU127028, BC016926, BU753483
    Consensus CDS
    CCDS3836.1
    UniProtKB/Swiss-Prot
    P42574
    Related
    ENSP00000311032, OTTHUMP00000165052, ENST00000308394, OTTHUMT00000257885
    Conserved Domains (1) summary
    cd00032
    Location:37275
    CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
  2. NM_032991.2NP_116786.1  caspase-3 preproprotein

    See proteins identical to NP_116786.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (beta) differs in the 5' UTR, compared to variant alpha.
    Source sequence(s)
    AU127028, BC016926, BU753483
    Consensus CDS
    CCDS3836.1
    UniProtKB/Swiss-Prot
    P42574
    Related
    ENSP00000428929, OTTHUMP00000165054, ENST00000523916, OTTHUMT00000257887
    Conserved Domains (1) summary
    cd00032
    Location:37275
    CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000004.12 

    Range
    184627696..184649475
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

  1. AC_000136.1 

    Range
    181303305..181324956
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018915.2 

    Range
    185525377..185547156
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)