Protein: Caspase-3 (CASP-3) (EC 3.4.22.56) (Apopain) (Cysteine protease CPP32) (CPP-32) (Protein Yama) (SREBP cleavage activity 1) (SCA-1) [Cleaved into: Caspase-3 subunit p17; Caspase-3 subunit p12] (P42574)
Organism: Homo sapiens (Human)
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. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage. 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.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:15003516}.
Sequence: MENTENSVDSKSIKNLEPKIIHGSESMDSGISLDNSYKMDYPEMGLCIIINNKNFHKSTGMTSRSGTDVDAANLRETFRNLKYEVRNKNDLTREEIVELMRDVSKEDHSKRSSFVCVLLSHGEEGIIFGTNGPVDLKKITNFFRGDRCRSLTGKPKLFIIQACRGTELDCGIETDSGVDDDMACHKIPVEADFLYAYSTAPGYYSWRNSKDGSWFIQSLCAMLKQYADKLEFMHILTRVNRKVATEFESFSFDATFHAKKQIPCIVSMLTKELYFYH
InterPro domains: - IPR011600: Peptidase C14, caspase domain (domain) [45-274]
- IPR015917: Peptidase C14A, caspase catalytic domain (domain) [36-277]
- IPR016129: Peptidase family C14A, His active site (active_site) [108-122]
- IPR002398: Peptidase C14 family (family) [7-275]
- IPR002138: Peptidase C14, caspase non-catalytic subunit p10 (domain) [183-277]
- IPR033139: Peptidase family C14A, cysteine active site (active_site) [154-165]
- IPR029030: Caspase-like domain superfamily (homologous_superfamily) [36-276]
- IPR001309: Peptidase C14, p20 domain (domain) [43-167]
Interaction partners: - Caspase-8
- E3 ubiquitin-protein ligase XIAP
- Poly [ADP-ribose] polymerase 1
- Caspase-9
- Apoptotic protease-activating factor 1
- Baculoviral IAP repeat-containing protein 2
- Cytochrome c
- Baculoviral IAP repeat-containing protein 3
- Cyclin-dependent kinase inhibitor 1
- DNA fragmentation factor subunit alpha
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:1901363 (heterocyclic compound binding), GO:0016787 (hydrolase activity), GO:0097159 (organic cyclic compound binding), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0008233 (peptidase activity), GO:0003723 (RNA binding), GO:0008234 (cysteine-type peptidase activity), GO:0004175 (endopeptidase activity), GO:0004197 (cysteine-type endopeptidase activity), GO:0097153 (cysteine-type endopeptidase activity involved in apoptotic process)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0008152 (metabolic process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0002376 (immune system process), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0023057 (negative regulation of signaling), GO:0042221 (response to chemical), GO:0006955 (immune response), GO:0051240 (positive regulation of multicellular organismal process), GO:0002684 (positive regulation of immune system process), GO:0006807 (nitrogen compound metabolic process), GO:0051239 (regulation of multicellular organismal process), GO:0009892 (negative regulation of metabolic process), GO:0009607 (response to biotic stimulus), GO:0008219 (cell death), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0002253 (activation of immune response), GO:0048523 (negative regulation of cellular process), GO:0051707 (response to other organism), GO:0007165 (signal transduction), GO:0009628 (response to abiotic stimulus), GO:0023056 (positive regulation of signaling), GO:0048584 (positive regulation of response to stimulus), GO:0019222 (regulation of metabolic process), GO:0002682 (regulation of immune system process), GO:0071704 (organic substance metabolic process), GO:0009893 (positive regulation of metabolic process), GO:0065009 (regulation of molecular function), GO:0006950 (response to stress), GO:0048585 (negative regulation of response to stimulus), GO:0007154 (cell communication), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:0009968 (negative regulation of signal transduction), GO:0032103 (positive regulation of response to external stimulus), GO:0012501 (programmed cell death), GO:0043207 (response to external biotic stimulus), GO:0060548 (negative regulation of cell death), GO:0080134 (regulation of response to stress), GO:0009966 (regulation of signal transduction), GO:0060255 (regulation of macromolecule metabolic process), GO:0032101 (regulation of response to external stimulus), GO:0001817 (regulation of cytokine production), GO:0002218 (activation of innate immune response), GO:2001021 (negative regulation of response to DNA damage stimulus), GO:0010035 (response to inorganic substance), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0097190 (apoptotic signaling pathway), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0050778 (positive regulation of immune response), GO:0001819 (positive regulation of cytokine production), GO:0031349 (positive regulation of defense response), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0002764 (immune response-regulating signaling pathway), GO:0009967 (positive regulation of signal transduction), GO:0050790 (regulation of catalytic activity), GO:0010648 (negative regulation of cell communication), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0044093 (positive regulation of molecular function), GO:1901564 (organonitrogen compound metabolic process), GO:0035556 (intracellular signal transduction), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0006979 (response to oxidative stress), GO:0019538 (protein metabolic process), GO:0006952 (defense response), GO:1901700 (response to oxygen-containing compound), GO:0030522 (intracellular receptor signaling pathway), GO:0031324 (negative regulation of cellular metabolic process), GO:0043170 (macromolecule metabolic process), GO:0010033 (response to organic substance), GO:0045087 (innate immune response), GO:0098542 (defense response to other organism), GO:0002831 (regulation of response to biotic stimulus), GO:0050776 (regulation of immune response), GO:0002757 (immune response-activating signaling pathway), GO:0010941 (regulation of cell death), GO:0010646 (regulation of cell communication), GO:0031325 (positive regulation of cellular metabolic process), GO:0070887 (cellular response to chemical stimulus), GO:0002833 (positive regulation of response to biotic stimulus), GO:0009617 (response to bacterium), GO:0051090 (regulation of DNA-binding transcription factor activity), GO:0009889 (regulation of biosynthetic process), GO:0010647 (positive regulation of cell communication), GO:0031323 (regulation of cellular metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0034599 (cellular response to oxidative stress), GO:0031347 (regulation of defense response), GO:0045089 (positive regulation of innate immune response), GO:0002758 (innate immune response-activating signaling pathway), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0043069 (negative regulation of programmed cell death), GO:0051246 (regulation of protein metabolic process), GO:0043067 (regulation of programmed cell death), GO:0010468 (regulation of gene expression), GO:0048660 (regulation of smooth muscle cell proliferation), GO:0043412 (macromolecule modification), GO:0038061 (NIK/NF-kappaB signaling), GO:0002753 (cytosolic pattern recognition receptor signaling pathway), GO:1902533 (positive regulation of intracellular signal transduction), GO:0051252 (regulation of RNA metabolic process), GO:0043085 (positive regulation of catalytic activity), GO:1901701 (cellular response to oxygen-containing compound), GO:0000302 (response to reactive oxygen species), GO:0051091 (positive regulation of DNA-binding transcription factor activity), GO:0034097 (response to cytokine), GO:0045088 (regulation of innate immune response), GO:0006508 (proteolysis), GO:2000377 (regulation of reactive oxygen species metabolic process), GO:0071310 (cellular response to organic substance), GO:0051336 (regulation of hydrolase activity), GO:0043068 (positive regulation of programmed cell death), GO:0062197 (cellular response to chemical stress), GO:0051248 (negative regulation of protein metabolic process), GO:0010506 (regulation of autophagy), GO:1902532 (negative regulation of intracellular signal transduction), GO:2001233 (regulation of apoptotic signaling pathway), GO:0010939 (regulation of necrotic cell death), GO:0043433 (negative regulation of DNA-binding transcription factor activity), GO:0036211 (protein modification process), GO:0050727 (regulation of inflammatory response), GO:0033993 (response to lipid), GO:0006915 (apoptotic process), GO:0031326 (regulation of cellular biosynthetic process), GO:0051247 (positive regulation of protein metabolic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0042542 (response to hydrogen peroxide), GO:0000302 (response to reactive oxygen species), GO:1902531 (regulation of intracellular signal transduction), GO:0042981 (regulation of apoptotic process), GO:0030162 (regulation of proteolysis), GO:0002221 (pattern recognition receptor signaling pathway), GO:0052547 (regulation of peptidase activity), GO:2001141 (regulation of RNA biosynthetic process), GO:0071345 (cellular response to cytokine stimulus), GO:0043549 (regulation of kinase activity), GO:0009411 (response to UV), GO:0034614 (cellular response to reactive oxygen species), GO:0051345 (positive regulation of hydrolase activity), GO:0034614 (cellular response to reactive oxygen species), GO:0043065 (positive regulation of apoptotic process), GO:0043066 (negative regulation of apoptotic process), GO:0070647 (protein modification by small protein conjugation or removal), GO:0006355 (regulation of DNA-templated transcription), GO:0033209 (tumor necrosis factor-mediated signaling pathway), GO:0071482 (cellular response to light stimulus), GO:0071396 (cellular response to lipid), GO:0045862 (positive regulation of proteolysis), GO:0043122 (regulation of I-kappaB kinase/NF-kappaB signaling), GO:0010803 (regulation of tumor necrosis factor-mediated signaling pathway), GO:0043123 (positive regulation of I-kappaB kinase/NF-kappaB signaling), GO:0070301 (cellular response to hydrogen peroxide), GO:0052548 (regulation of endopeptidase activity), GO:0010466 (negative regulation of peptidase activity), GO:0043154 (negative regulation of cysteine-type endopeptidase activity involved in apoptotic process), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0032446 (protein modification by small protein conjugation), GO:0034644 (cellular response to UV), GO:2000116 (regulation of cysteine-type endopeptidase activity), GO:0016567 (protein ubiquitination), GO:0010951 (negative regulation of endopeptidase activity), GO:0000209 (protein polyubiquitination), GO:0043281 (regulation of cysteine-type endopeptidase activity involved in apoptotic process), GO:2000117 (negative regulation of cysteine-type endopeptidase activity)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0016020 (membrane), GO:0044297 (cell body), GO:0005829 (cytosol), GO:1902494 (catalytic complex), GO:0036477 (somatodendritic compartment), GO:0005737 (cytoplasm), GO:0071944 (cell periphery), GO:0098796 (membrane protein complex), GO:0098797 (plasma membrane protein complex), GO:0043025 (neuronal cell body), GO:0098857 (membrane microdomain), GO:1905368 (peptidase complex), GO:0005886 (plasma membrane), GO:0045121 (membrane raft), GO:1905369 (endopeptidase complex), GO:0008303 (caspase complex)