Caspase-7
Also known as: CASP7, MCH3
Function
Thiol protease involved in different programmed cell death processes, such as apoptosis, pyroptosis or granzyme-mediated programmed cell death, by proteolytically cleaving target proteins. Has a marked preference for Asp-Glu-Val-Asp (DEVD) consensus sequences, with some plasticity for alternate non-canonical sequences. Its involvement in the different programmed cell death processes is probably determined by upstream proteases that activate CASP7 (By similarity). Acts as an 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 proteins, such as CLSPN, PARP1, PTGES3 and YY1. Compared to CASP3, acts as a minor executioner caspase and cleaves a limited set of target proteins. Acts as a key regulator of the inflammatory response in response to bacterial infection by catalyzing cleavage and activation of the sphingomyelin phosphodiesterase SMPD1 in the extracellular milieu, thereby promoting membrane repair. Regulates pyroptosis in intestinal epithelial cells: cleaved and activated by CASP1 in response to S.typhimurium infection, promoting its secretion to the extracellular milieu, where it catalyzes activation of SMPD1, generating ceramides that repair membranes and counteract the action of gasdermin-D (GSDMD) pores (By similarity). Regulates granzyme-mediated programmed cell death in hepatocytes: cleaved and activated by granzyme B (GZMB) in response to bacterial infection, promoting its secretion to the extracellular milieu, where it catalyzes activation of SMPD1, generating ceramides that repair membranes and counteract the action of perforin (PRF1) pores (By similarity). Following cleavage by CASP1 in response to inflammasome activation, catalyzes processing and inactivation of PARP1, alleviating the transcription repressor activity of PARP1. 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 (By similarity). Cleaves and activates sterol regulatory element binding proteins (SREBPs). Cleaves phospholipid scramblase proteins XKR4, XKR8 and XKR9 (By similarity). In case of infection, catalyzes cleavage of Kaposi sarcoma-associated herpesvirus protein ORF57, thereby preventing expression of viral lytic genes. 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 · 47
- 1F1J X-ray 2.35A
- 1GQF X-ray 2.90A
- 1I4O X-ray 2.40A
- 1I51 X-ray 2.45A
- 1K86 X-ray 2.60A
- 1K88 X-ray 2.70A
- 1KMC X-ray 2.90A
- 1SHJ X-ray 2.80A
- 1SHL X-ray 3.00A
- 2QL5 X-ray 2.34A
- 2QL7 X-ray 2.40A
- 2QL9 X-ray 2.14A
- … and 35 more
A predicted model is available from AlphaFold.
Gene Ontology · 20
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0005615 extracellular space
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0004190 aspartic-type endopeptidase activity
- GO:0004197 cysteine-type endopeptidase activity
- GO:0008234 cysteine-type peptidase activity
- GO:0008233 peptidase activity
- GO:0003723 RNA binding
- GO:0006915 apoptotic process
- GO:0071222 cellular response to lipopolysaccharide
- GO:0072734 cellular response to staurosporine
- GO:0097194 execution phase of apoptosis
- GO:0070227 lymphocyte apoptotic process
- GO:0043525 positive regulation of neuron apoptotic process
- GO:0030163 protein catabolic process
- GO:0051604 protein maturation
- GO:0006508 proteolysis
- GO:0051146 striated muscle cell differentiation
Drugs targeting this protein · 1
- EMRICASAN inhibitor
Related proteins · sequence + function similarity
Co-cited proteins · studied together in the literature
- Caspase-3 12 shared papers
- Caspase-7 1 shared papers
- Endosome/lysosome-associated apoptosis and autophagy regulator 1 1 shared papers
- Calpain-1 catalytic subunit 1 shared papers
- Prostaglandin E synthase 3 2 shared papers
- Caspase-9 7 shared papers
- Ataxin-7 1 shared papers
- Post-transcriptional regulator MTA 1 shared papers
- E3 ubiquitin-protein ligase XIAP 4 shared papers
- Serine/threonine-protein kinase PAK 2 2 shared papers
- Caspase-7 2 shared papers
- Sphingomyelin phosphodiesterase 1 shared papers
Literature · 54 cited papers
- 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
- 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
- Characterization of caspase-7 interaction with RNA. Biochem. J. · 2021
- Caspase-7 uses RNA to enhance proteolysis of poly(ADP-ribose) polymerase 1 and other RNA-binding proteins. Proc. Natl. Acad. Sci. U.S.A. · 2019
- Physiological and pathophysiological characteristics of ataxin-3 isoforms. J. Biol. Chem. · 2019
- Characterization of Hsp90 co-chaperone p23 cleavage by caspase-7 uncovers a peptidase-substrate interaction involving intrinsically disordered regions. Biochemistry · 2017
- Dual site phosphorylation of caspase-7 by PAK2 blocks apoptotic activity by two distinct mechanisms. Structure · 2017
- Reprogramming caspase-7 specificity by regio-specific mutations and selection provides alternate solutions for substrate recognition. ACS Chem. Biol. · 2016
- KIAA1324 Suppresses Gastric Cancer Progression by Inhibiting the Oncoprotein GRP78. Cancer Res. · 2015
- Combined inhibition of caspase 3 and caspase 7 by two highly selective DARPins slows down cellular demise. Biochem. J. · 2014
- … and 42 more in the literature graph