Caspase-3
Also known as: CASP3, CPP32
Function
Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis. Following cleavage and activation by initiator caspases (CASP8, CASP9 and/or CASP10), mediates execution of apoptosis by catalyzing cleavage of many proteins. At the onset of apoptosis, it proteolytically cleaves poly(ADP-ribose) polymerase PARP1 at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain (By similarity). Cleaves and activates caspase-6, -7 and -9 (CASP6, CASP7 and CASP9, respectively). Cleaves and inactivates interleukin-18 (IL18). Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage. Also involved in axon pruning during brain development (By similarity). Cleaves DSG2 in response to apoptosis resulting in a loss of full length DSG2 at desmosome cell junctions and subsequent loss of cell-cell adhesion. Also cleaves JUP in response to apoptosis. Cleaves and inhibits serine/threonine-protein kinase AKT1 in response to oxidative stress. Acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine overproduction. Also involved in pyroptosis by mediating cleavage and activation of gasdermin-E (GSDME). Cleaves XRCC4 and phospholipid scramblase proteins XKR4, XKR8 and XKR9, leading to promote phosphatidylserine exposure on apoptotic cell surface. Cleaves BIRC6 following inhibition of BIRC6-caspase binding by DIABLO/SMAC.
Classification
- Family (Pfam)
- PF00656 Peptidase_C14
- InterPro
- Caspase-like_dom_sf, Caspase_cys_AS, Caspase_his_AS, Pept_C14, Pept_C14_caspase, Pept_C14_p10, Pept_C14_p20, Pept_C14A
- Functional cluster
- Ribosome-Recycling & Clp Protease Factors
Experimental structures · PDB · 135
- 1CP3 X-ray 2.30A
- 1GFW X-ray 2.80A
- 1I3O X-ray 2.70A
- 1NME X-ray 1.60A
- 1NMQ X-ray 2.40A
- 1NMS X-ray 1.70A
- 1PAU X-ray 2.50A
- 1QX3 X-ray 1.90A
- 1RE1 X-ray 2.50A
- 1RHJ X-ray 2.20A
- 1RHK X-ray 2.50A
- 1RHM X-ray 2.50A
- … and 123 more
A predicted model is available from AlphaFold.
Gene Ontology · 64
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0031264 death-inducing signaling complex
- GO:0098978 glutamatergic synapse
- GO:0043025 neuronal cell body
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0014069 postsynaptic density
- GO:0004190 aspartic-type endopeptidase activity
- GO:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity
- GO:0004197 cysteine-type endopeptidase activity
- GO:0005123 death receptor binding
- GO:0008047 enzyme activator activity
- GO:0008233 peptidase activity
- GO:0016005 phospholipase A2 activator activity
- GO:0002020 protease binding
- GO:0044877 protein-containing complex binding
- GO:0006915 apoptotic process
- GO:0097190 apoptotic signaling pathway
- GO:0007413 axonal fasciculation
- GO:0072734 cellular response to staurosporine
- GO:0030218 erythrocyte differentiation
- GO:0097194 execution phase of apoptosis
- GO:0034349 glial cell apoptotic process
- GO:0021766 hippocampus development
- GO:0097193 intrinsic apoptotic signaling pathway
- GO:0008627 intrinsic apoptotic signaling pathway in response to osmotic stress
- GO:0030216 keratinocyte differentiation
- GO:0007611 learning or memory
- GO:0071887 leukocyte apoptotic process
- GO:0001554 luteolysis
- GO:0001818 negative regulation of cytokine production
- GO:0030182 neuron differentiation
- GO:0048011 neurotrophin TRK receptor signaling pathway
- GO:0030220 platelet formation
- GO:1902004 positive regulation of amyloid-beta formation
- GO:0043525 positive regulation of neuron apoptotic process
- GO:0140639 positive regulation of pyroptotic inflammatory response
- GO:0030163 protein catabolic process
- GO:0051604 protein maturation
- GO:0016485 protein processing
- GO:0006508 proteolysis
- GO:0070269 pyroptotic inflammatory response
- GO:0016241 regulation of macroautophagy
- GO:0031647 regulation of protein stability
- GO:0098693 regulation of synaptic vesicle cycle
- GO:0043200 response to amino acid
- GO:0072347 response to anesthetic
- GO:0032025 response to cobalt ion
- GO:0032355 response to estradiol
- GO:0045471 response to ethanol
- GO:0051384 response to glucocorticoid
- GO:0009749 response to glucose
- GO:0042542 response to hydrogen peroxide
- GO:0001666 response to hypoxia
- GO:1990418 response to insulin-like growth factor stimulus
- GO:0032496 response to lipopolysaccharide
- GO:0035094 response to nicotine
- GO:0034612 response to tumor necrosis factor
- GO:0010165 response to X-ray
- GO:0009410 response to xenobiotic stimulus
- GO:0051146 striated muscle cell differentiation
- GO:0036269 swimming behavior
- GO:0098883 synapse pruning
Drugs targeting this protein · 1
- EMRICASAN inhibitor
Related proteins · sequence + function similarity
Co-cited proteins · studied together in the literature
- Caspase-7 12 shared papers
- Gasdermin-E 2 shared papers
- 2-oxoglutarate dehydrogenase-like, mitochondrial 1 shared papers
- Gasdermin-E 2 shared papers
- Poly [ADP-ribose] polymerase 1 3 shared papers
- Arginine ADP-riboxanase CopC 3 shared papers
- Huntingtin 1 shared papers
- Dual E2 ubiquitin-conjugating enzyme/E3 ubiquitin-protein ligase BIRC6 3 shared papers
- Diablo IAP-binding mitochondrial protein 3 shared papers
- Proto-oncogene tyrosine-protein kinase receptor Ret 1 shared papers
- Interleukin-18 2 shared papers
- Caspase-9 4 shared papers
Literature · 37 cited papers
- Recognition and maturation of IL-18 by caspase-4 noncanonical inflammasome. Nature · 2023
- Structural basis for SMAC-mediated antagonism of caspase inhibition by the giant ubiquitin ligase BIRC6. Science · 2023
- Structures of BIRC6-client complexes provide a mechanism of SMAC-mediated release of caspases. Science · 2023
- Structural insights into caspase ADPR deacylization catalyzed by a bacterial effector and host calmodulin. Mol. Cell · 2022
- Calmodulin binding activates chromobacterium CopC effector to ADP-riboxanate host apoptotic caspases. MBio · 2022
- Pathogen hijacks programmed cell death signaling by arginine ADPR-deacylization of caspases. Mol. Cell · 2022
- Caspase cleavage releases a nuclear protein fragment that stimulates phospholipid scrambling at the plasma membrane. Mol. Cell · 2021
- Apoptotic caspases suppress type i interferon production via the cleavage of cGAS, MAVS, and IRF3. Mol. Cell · 2019
- Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature · 2017
- Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic/pyroptotic cell death. Nat. Commun. · 2017
- Xk-Related protein 8 and CED-8 promote phosphatidylserine exposure in apoptotic cells. Science · 2013
- Structural snapshots reveal distinct mechanisms of procaspase-3 and -7 activation. Proc. Natl. Acad. Sci. U.S.A. · 2013
- … and 25 more in the literature graph