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CASP3 caspase 3 [ Homo sapiens (human) ]

Gene ID: 836, updated on 7-Jun-2020

Summary

Official Symbol
CASP3provided by HGNC
Official Full Name
caspase 3provided by HGNC
Primary source
HGNC:HGNC:1504
See related
Ensembl:ENSG00000164305 MIM:600636
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
The protein encoded by this gene is a cysteine-aspartic acid protease that plays a central role in the execution-phase of cell apoptosis. The encoded protein cleaves and inactivates poly(ADP-ribose) polymerase while it cleaves and activates sterol regulatory element binding proteins as well as caspases 6, 7, and 9. This 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. [provided by RefSeq, Aug 2017]
Expression
Ubiquitous expression in duodenum (RPKM 26.8), small intestine (RPKM 21.6) and 25 other tissues See more
Orthologs

Genomic context

See CASP3 in Genome Data Viewer
Location:
4q35.1
Exon count:
9
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 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 GAR1 ribonucleoprotein homolog (yeast) pseudogene Neighboring gene long intergenic non-protein coding RNA 2365 Neighboring gene primase and DNA directed polymerase Neighboring gene centromere protein U Neighboring gene acyl-CoA synthetase long chain family member 1 Neighboring gene proteoglycan 3, pro eosinophil major basic protein 2 pseudogene

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HIV-1 interactions

Replication interactions

Interaction Pubs
In vitro infection with HIV-1 subtype B activates caspase-3 in neuronal cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 Env gp120 upregulates Caspase-3 in SVGA cells PubMed
env Mutational analysis shows that HIV-1 gp120 R476K and N425R are associated with the bystander apoptosis-inducing activity of Env glycoprotein through caspase 3 PubMed
env Treatment of astrocytes with HIV-1 gp120 induces the cleavage of CASP3 as compared with untreated cells PubMed
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 surface glycoprotein gp160, precursor env HIV-1 Env from Yu-2 and primary isolates activate Caspase-3 and Caspase-7 in bystander cells of co-culture assays PubMed
env HIV-1 gp120- and gp160-induced apoptosis in cell cultures through binding to CXCR4 involves protein kinase C, basic fibroblast growth factor, caspase-3, and pro-apoptotic molecule Bax 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 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
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
Pr55(Gag) gag Monocyte-derived macrophages selectively capture and engulf HIV-1-infected CD4+ T cells as HIV-1 Gag interacts with CD3 and Caspase 3 markers, leading to efficient macrophage infection PubMed
Tat tat HIV-1 clade B and C Tat induce cleavage of both PARP and CASP3 in primary glia PubMed
tat CB1 and CB2 endocannabinoid receptors are involved in HIV-1 Tat-induced cleavage of PARP1 and CASP3 in retinal cells PubMed
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 Visualization of HIV-1 Vpr-induced cell cycle arrest in G2 phase and apoptosis in HeLa/Fucci2 cells is associated with caspase-3 activation PubMed
vpr Through activation of the caspase 9 pathway, HIV-1 Vpr also activates caspase 3 PubMed
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
Vpu vpu Caspase-8 and caspase-3 activity are required for HIV-1 Vpu-induced cleavage of IRF3 and HIV-1 infection also induces caspase-mediated IRF3 cleavage PubMed
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

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

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
 
anterior neural tube closure IEA
Inferred from Electronic Annotation
more info
 
apoptotic DNA fragmentation TAS
Traceable Author Statement
more info
 
apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
apoptotic signaling pathway TAS
Traceable Author Statement
more info
PubMed 
axonal fasciculation IEA
Inferred from Electronic Annotation
more info
 
cell fate commitment IEA
Inferred from Electronic Annotation
more info
 
cellular response to DNA damage stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to staurosporine IMP
Inferred from Mutant Phenotype
more info
PubMed 
cytokine-mediated signaling pathway TAS
Traceable Author Statement
more info
 
erythrocyte differentiation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 
execution phase of apoptosis TAS
Traceable Author Statement
more info
 
extrinsic apoptotic signaling pathway in absence of ligand TAS
Traceable Author Statement
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
 
hippocampus development IEA
Inferred from Electronic Annotation
more info
 
intrinsic apoptotic signaling pathway in response to osmotic stress IEA
Inferred from Electronic Annotation
more info
 
keratinocyte differentiation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
learning or memory IEA
Inferred from Electronic Annotation
more info
 
leukocyte apoptotic process IEA
Inferred from Electronic Annotation
more info
 
luteolysis IEA
Inferred from Electronic Annotation
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
PubMed 
neurotrophin TRK receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
platelet formation TAS
Traceable Author Statement
more info
PubMed 
positive regulation of amyloid-beta formation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of catalytic activity IEA
Inferred from Electronic Annotation
more info
 
positive regulation of neuron apoptotic process IEA
Inferred from Electronic Annotation
more info
 
protein processing IEA
Inferred from Electronic Annotation
more info
 
proteolysis IDA
Inferred from Direct Assay
more info
PubMed 
regulation of macroautophagy TAS
Traceable Author Statement
more info
PubMed 
regulation of protein stability IDA
Inferred from Direct Assay
more info
PubMed 
response to UV IEA
Inferred from Electronic Annotation
more info
 
response to X-ray IEA
Inferred from Electronic Annotation
more info
 
response to amino acid IEA
Inferred from Electronic Annotation
more info
 
response to cobalt ion IEA
Inferred from Electronic Annotation
more info
 
response to estradiol IEA
Inferred from Electronic Annotation
more info
 
response to glucocorticoid IEA
Inferred from Electronic Annotation
more info
 
response to glucose IEA
Inferred from Electronic Annotation
more info
 
response to hydrogen peroxide IEA
Inferred from Electronic Annotation
more info
 
response to hypoxia IEA
Inferred from Electronic Annotation
more info
 
response to lipopolysaccharide IEA
Inferred from Electronic Annotation
more info
 
response to nicotine IEA
Inferred from Electronic Annotation
more info
 
response to tumor necrosis factor TAS
Traceable Author Statement
more info
PubMed 
sensory perception of sound IEA
Inferred from Electronic Annotation
more info
 
striated muscle cell differentiation IEA
Inferred from Electronic Annotation
more info
 
wound healing IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
death-inducing signaling complex IEA
Inferred from Electronic Annotation
more info
 
membrane raft IEA
Inferred from Electronic Annotation
more info
 
neuronal cell body IEA
Inferred from Electronic Annotation
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
caspase-3
Names
CASP-3
CPP-32
PARP cleavage protease
SREBP cleavage activity 1
apopain
caspase 3, apoptosis-related cysteine peptidase
caspase 3, apoptosis-related cysteine protease
cysteine protease CPP32
procaspase3
protein Yama
NP_001341706.1
NP_001341708.1
NP_001341709.1
NP_001341710.1
NP_001341711.1
NP_001341712.1
NP_001341713.1
NP_004337.2
NP_116786.1

NCBI Reference Sequences (RefSeq)

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_001354777.1NP_001341706.1  caspase-3 isoform a preproprotein

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2, and 3 all encode the same isoform (a).
    Source sequence(s)
    AC073932, AC079257
    Consensus CDS
    CCDS3836.1
    Conserved Domains (1) summary
    smart00115
    Location:37277
    CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues
  2. NM_001354779.1NP_001341708.1  caspase-3 isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5), as well as variant 6, encodes isoform b.
    Source sequence(s)
    AC073932, AC079257
    Conserved Domains (1) summary
    smart00115
    Location:11251
    CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues
  3. NM_001354780.1NP_001341709.1  caspase-3 isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6), as well as variant 5, encodes isoform b.
    Source sequence(s)
    AC073932, AC079257
    Conserved Domains (1) summary
    smart00115
    Location:11251
    CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues
  4. NM_001354781.1NP_001341710.1  caspase-3 isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7), as well as variant 8, encodes isoform c.
    Source sequence(s)
    AC073932, AC079257
    Consensus CDS
    CCDS87283.1
    Related
    ENSP00000377213.4, ENST00000393588.8
    Conserved Domains (1) summary
    cl00042
    Location:37161
    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 ...
  5. NM_001354782.1NP_001341711.1  caspase-3 isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8), as well as variant 7, encodes isoform c.
    Source sequence(s)
    AC073932, AC079257
    Consensus CDS
    CCDS87283.1
    Related
    ENSP00000428372.1, ENST00000517513.5
    Conserved Domains (1) summary
    cl00042
    Location:37161
    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 ...
  6. NM_001354783.1NP_001341712.1  caspase-3 isoform d

    Status: REVIEWED

    Source sequence(s)
    AC073932, AC079257
    Conserved Domains (1) summary
    cl00042
    Location:46170
    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 ...
  7. NM_001354784.1NP_001341713.1  caspase-3 isoform e

    Status: REVIEWED

    Source sequence(s)
    AC073932, AC079257
    Conserved Domains (1) summary
    cl00042
    Location:11135
    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 ...
  8. NM_004346.4NP_004337.2  caspase-3 isoform a preproprotein

    See identical proteins and their annotated locations for NP_004337.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1, also known as alpha) encodes the longest isoform (a). Variants 1, 2, and 3 all encode the same isoform (a).
    Source sequence(s)
    AU127028, BC016926, BU753483
    Consensus CDS
    CCDS3836.1
    UniProtKB/Swiss-Prot
    P42574
    Related
    ENSP00000311032.4, ENST00000308394.9
    Conserved Domains (1) summary
    smart00115
    Location:37277
    CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues
  9. NM_032991.2NP_116786.1  caspase-3 isoform a preproprotein

    See identical proteins and their annotated locations for NP_116786.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2, also known as beta) differs in the 5' UTR compared to variant 1. Variants 1, 2, and 3 all encode the same isoform (a).
    Source sequence(s)
    AU127028, BC016926, BU753483
    Consensus CDS
    CCDS3836.1
    UniProtKB/Swiss-Prot
    P42574
    Related
    ENSP00000428929.1, ENST00000523916.5
    Conserved Domains (1) summary
    smart00115
    Location:37277
    CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p13 Primary Assembly

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