Caspase-2

Function

Is a regulator of the cascade of caspases responsible for apoptosis execution. Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival. Associates with PIDD1 and CRADD to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis in response to genotoxic stress.

Classification

Family (Pfam)

PF00619 CARD, PF00656 Peptidase_C14

InterPro

CARD, CASP2_CARD, 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 · 17

• 1PYO X-ray 1.65A
• 2P2C X-ray 3.24A
• 3R5J X-ray 1.77A
• 3R6G X-ray 2.07A
• 3R6L X-ray 1.90A
• 3R7B X-ray 1.80A
• 3R7N X-ray 2.33A
• 3R7S X-ray 2.25A
• 3RJM X-ray 2.55A
• 6GKF X-ray 2.60A
• 6GKG X-ray 2.85A
• 6S9K X-ray 1.60A
• … and 5 more

A predicted model is available from AlphaFold.

Gene Ontology · 23

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005739 mitochondrion
• GO:0005730 nucleolus
• GO:0005634 nucleus
• GO:0004197 cysteine-type endopeptidase activity
• GO:0019899 enzyme binding
• GO:0042802 identical protein binding
• GO:0019904 protein domain specific binding
• GO:0006915 apoptotic process
• GO:0097190 apoptotic signaling pathway
• GO:0071260 cellular response to mechanical stimulus
• GO:0006974 DNA damage response
• GO:0030330 DNA damage response, signal transduction by p53 class mediator
• GO:0097194 execution phase of apoptosis
• GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
• GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
• GO:0001554 luteolysis
• GO:0043066 negative regulation of apoptotic process
• GO:0003407 neural retina development
• GO:0043065 positive regulation of apoptotic process
• GO:0043525 positive regulation of neuron apoptotic process
• GO:0016485 protein processing

Disease associations

• intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly MONDO:0957999

Drugs targeting this protein · 1

• EMRICASAN inhibitor

Related proteins · sequence + function similarity

• Caspase-2 0.99
• Caspase-2 0.99
• Caspase-2 0.92
• CASP8 and FADD-like apoptosis regulator 0.79
• Caspase-10 0.79
• Caspase-8 0.79
• CASP8 and FADD-like apoptosis regulator 0.78
• CASP8 and FADD-like apoptosis regulator 0.78
• Caspase-8 0.76
• Caspase-14 0.75
• Caspase-9 0.75
• Caspase-9 0.75

Co-cited proteins · studied together in the literature

• IML2-like protein YKR018C 1 shared papers
• Death domain-containing protein CRADD 4 shared papers
• Nucleolar protein 3 1 shared papers
• p53-induced death domain-containing protein 1 2 shared papers
• Cell death protein 3 1 shared papers
• Receptor-interacting serine/threonine-protein kinase 1 1 shared papers

Literature · 17 cited papers

• Bi-allelic truncating variants in CASP2 underlie a neurodevelopmental disorder with lissencephaly. Eur. J. Hum. Genet. · 2024
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
• Functional connection between p53 and caspase-2 is essential for apoptosis induced by DNA damage. Oncogene · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress. Science · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• Crystal structure of caspase-2, apical initiator of the intrinsic apoptotic pathway. J. Biol. Chem. · 2003
• The DNA sequence of human chromosome 7. Nature · 2003
• Identification of a caspase-2 isoform that behaves as an endogenous inhibitor of the caspase cascade. Cancer Res. · 2000
• … and 5 more in the literature graph