Caspase-9

Function

Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates effector caspases caspase-3 (CASP3) or caspase-7 (CASP7). Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP). Cleaves BIRC6 following inhibition of BIRC6-caspase binding by DIABLO/SMAC.

Classification

Family (Pfam)

PF00619 CARD, PF00656 Peptidase_C14

InterPro

CARD, CARD_CASP9, Caspase-like_dom_sf, Caspase_cys_AS, Caspase_his_AS, DEATH-like_dom_sf, Pept_C14, Pept_C14_caspase, Pept_C14_p10, Pept_C14_p20, Pept_C14A

Functional cluster

Eukaryotic Transcription Factors & related

Experimental structures · PDB · 10

• 1JXQ X-ray 2.80A
• 1NW9 X-ray 2.40A
• 2AR9 X-ray 2.80A
• 3D9T X-ray 1.50A
• 3V3K X-ray 3.49A
• 3YGS X-ray 2.50A
• 4RHW X-ray 2.10A
• 5JUY EM 4.10A
• 5WVC X-ray 2.99A
• 5WVE EM 4.40A

A predicted model is available from AlphaFold.

Gene Ontology · 35

• GO:0043293 apoptosome
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005739 mitochondrion
• GO:0005634 nucleus
• GO:0032991 protein-containing complex
• GO:0004197 cysteine-type endopeptidase activity
• GO:0008047 enzyme activator activity
• GO:0042802 identical protein binding
• GO:0008233 peptidase activity
• GO:0019901 protein kinase binding
• GO:0006915 apoptotic process
• GO:0071549 cellular response to dexamethasone stimulus
• GO:0034644 cellular response to UV
• GO:0006974 DNA damage response
• GO:0034349 glial cell apoptotic process
• GO:0097193 intrinsic apoptotic signaling pathway
• GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
• GO:0001822 kidney development
• GO:0071887 leukocyte apoptotic process
• GO:0030220 platelet formation
• GO:0043065 positive regulation of apoptotic process
• GO:1900119 positive regulation of execution phase of apoptosis
• GO:0043525 positive regulation of neuron apoptotic process
• GO:0051604 protein maturation
• GO:0016485 protein processing
• GO:0072347 response to anesthetic
• GO:0032025 response to cobalt ion
• GO:0032355 response to estradiol
• GO:0045471 response to ethanol
• GO:0001666 response to hypoxia
• GO:0071680 response to indole-3-methanol
• GO:0002931 response to ischemia
• GO:0032496 response to lipopolysaccharide
• GO:0042770 signal transduction in response to DNA damage

Drugs targeting this protein · 2

• EMRICASAN inhibitor
• NIVOCASAN inhibitor

Related proteins · sequence + function similarity

• Caspase-9 0.96
• Caspase-8 0.78
• Caspase-2 0.77
• Caspase-2 0.76
• Caspase-2 0.75
• Caspase-8 0.75
• Caspase-10 0.74
• Caspase-6 0.73
• Caspase-6 0.73
• Putative inactive caspase B 0.72
• Caspase-3 0.71
• Caspase b 0.69

Co-cited proteins · studied together in the literature

• EF-hand domain-containing protein D2 1 shared papers
• Caspase-9 1 shared papers
• Caspase-6 2 shared papers
• Effector protein NleF 1 shared papers
• Caspase-7 7 shared papers
• E3 ubiquitin-protein ligase XIAP 3 shared papers
• HCLS1-associated protein X-1 1 shared papers
• Dual E2 ubiquitin-conjugating enzyme/E3 ubiquitin-protein ligase BIRC6 3 shared papers
• Huntingtin-interacting protein 1-related protein 1 shared papers
• Diablo IAP-binding mitochondrial protein 3 shared papers
• Bcl-2-like protein 10 1 shared papers
• Serine protease HTRA2, mitochondrial 2 shared papers

Literature · 28 cited papers

• Structural basis for SMAC-mediated antagonism of caspase inhibition by the giant ubiquitin ligase BIRC6. Science · 2023
• Structural basis for regulation of apoptosis and autophagy by the BIRC6/SMAC complex. 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
• Dual site phosphorylation of caspase-7 by PAK2 blocks apoptotic activity by two distinct mechanisms. Structure · 2017
• The E. coli effector protein NleF is a caspase inhibitor. PLoS ONE · 2013
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
• HIP1R interacts with a member of Bcl-2 family, BCL2L10, and induces BAK-dependent cell death. Cell. Physiol. Biochem. · 2009
• Comparative proteomics analysis of caspase-9-protein complexes in untreated and cytochrome c/dATP stimulated lysates of NSCLC cells. J. Proteomics · 2009
• A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
• Engineered hybrid dimers: tracking the activation pathway of caspase-7. Mol. Cell · 2006
• … and 16 more in the literature graph