Caspase-3 (CASP3)
The protein contains 277 amino acids for an estimated molecular weight of 31608 Da.
Involved in the activation cascade of caspases responsible for apoptosis execution (PubMed:7596430). At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond (PubMed:7774019). Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9 (PubMed:7596430). Involved in the cleavage of huntingtin (PubMed:8696339). Triggers cell adhesion in sympathetic neurons through RET cleavage (PubMed:21357690). Cleaves and inhibits serine/threonine-protein kinase AKT1 in response to oxidative stress (PubMed:23152800). (updated: April 7, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs35578277 | |
| dbSNP:rs1049210 |
Biological Process
Activation of cysteine-type endopeptidase activity involved in apoptotic process
Activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c
Anterior neural tube closure
Apoptotic DNA fragmentation
Apoptotic process
Apoptotic signaling pathway
Axonal fasciculation
B cell homeostasis
Cell fate commitment
Cellular component disassembly involved in execution phase of apoptosis
Cellular response to DNA damage stimulus
Cellular response to staurosporine
Cytokine-mediated signaling pathway
Erythrocyte differentiation
Execution phase of apoptosis
Extracellular matrix disassembly
Extracellular matrix organization
Extrinsic apoptotic signaling pathway in absence of ligand
Extrinsic apoptotic signaling pathway via death domain receptors
Glial cell apoptotic process
Heart development
Hippo signaling
Hippocampus development
Intrinsic apoptotic signaling pathway
Intrinsic apoptotic signaling pathway in response to osmotic stress
Intrinsic apoptotic signaling pathway in response to oxidative stress
Keratinocyte differentiation
Learning or memory
Leukocyte apoptotic process
Luteolysis
Negative regulation of activated T cell proliferation
Negative regulation of apoptotic process
Negative regulation of B cell proliferation
Negative regulation of cyclin-dependent protein serine/threonine kinase activity
Neuron apoptotic process
Neuron differentiation
Neurotrophin TRK receptor signaling pathway
Platelet formation
Positive regulation of amyloid-beta formation
Positive regulation of apoptotic process
Positive regulation of neuron apoptotic process
Protein processing
Proteolysis
Regulation of apoptotic DNA fragmentation
Regulation of cysteine-type endopeptidase activity involved in apoptotic process
Regulation of macroautophagy
Regulation of protein stability
Release of cytochrome c from mitochondria
Response to amino acid
Response to antibiotic
Response to cobalt ion
Response to drug
Response to estradiol
Response to glucocorticoid
Response to glucose
Response to hydrogen peroxide
Response to hypoxia
Response to lipopolysaccharide
Response to nicotine
Response to tumor necrosis factor
Response to UV
Response to wounding
Response to X-ray
Sensory perception of sound
Striated muscle cell differentiation
T cell homeostasis
Wound healing
Cellular Component
Cytoplasm
Cytosol
Death-inducing signaling complex
Membrane raft
Neuronal cell body
Nucleoplasm
Nucleus
Plasma membrane
Molecular Function
Aspartic-type endopeptidase activity
Cyclin-dependent protein serine/threonine kinase inhibitor activity
Cysteine-type endopeptidase activator activity involved in apoptotic process
Cysteine-type endopeptidase activity
Cysteine-type endopeptidase activity involved in apoptotic process
Cysteine-type endopeptidase activity involved in apoptotic signaling pathway
Cysteine-type endopeptidase activity involved in execution phase of apoptosis
Death receptor binding
Peptidase activity
Phospholipase A2 activator activity
Protease binding
Protein complex binding
Protein-containing complex binding
The reference OMIM entry for this protein is 600636
Caspase 3, apoptosis-related cysteine protease; casp3
Parp cleavage protease
Apopain
Cpp32
Yama
DESCRIPTION
Cysteinyl aspartate-specific proteases, or caspases, such as CASP3, cleave substrates directly after an aspartic acid residue and play essential roles in programmed cell death. Caspases are synthesized in a dormant form with an N-terminal prodomain followed by a large subunit and a small subunit. Proteolytic processing releases the caspase large and small subunits, resulting in activation (summary by Parker et al., 2010).CLONING
Fernandes-Alnemri et al. (1994) cloned a gene encoding a 277-amino acid, 32-kD putative cysteine protease that they designated CPP32 from human Jurkat T cells. The CPP32 proenzyme undergoes proteolytic cleavage to produce 2 subunits, termed p20 and p11, which dimerize to form the active enzyme. CPP32 shares significant homology with mammalian ICE (CASP1; 147678), mouse Nedd2 (CASP2; 600639), and the Caenorhabditis elegans cell death protein Ced3. CPP32 showed highest expression in cell lines of lymphocytic origin. By searching EST databases for sequences encoding the pentapeptide motif QACRG, which encompasses the catalytic cysteine of ICE, followed by screening an umbilical vein endothelial cell cDNA library, Tewari et al. (1995) cloned CASP3, which they called Yama after the Hindu god of death. Huang et al. (2001) identified and cloned a short CASP3 splice variant, which they called CASP3s, from a human carcinoma cell line. CASP3s appeared to result from a deletion of exon 6 that shifts the reading frame in the C terminus, leading to an altered amino acid sequence and a truncated polypeptide. The deduced 182-amino acid protein contains the complete N terminus but is missing 95 residues at the C terminus, including the conserved QACRG sequence at the catalytic site. PCR analysis of 16 human tissues revealed expression of full-length CASP3, as well as CASP3s at somewhat lower levels, in all tissues tested. Western blot analysis of 3 cell lines revealed the prominent CASP3 band at 32 kD and CASP3s at 20 kD. Several human cancer cell lines showed coexpression of both variants at the mRNA and protein levels. Overexpression of the catalytically inactive CASP3s by human kidney cells offered some resistance to inducers of apoptosis, and CASP3s accumulation could be enhanced with addition of proteasome inhibitors.GENE FUNCTION
Fernandes-Alnemri et al. (1994) found that overexpression of CPP32 in insect cells induced apoptosis. Coexpression of the 2 CPP32 subunits in insect cells also resulted in apoptosis. An early event that occurs concomitantly with the onset of apoptosis is the proteolytic breakdown of poly(ADP-ribose) polymerase (PARP; 173870) by a protease with properties resembling those of caspase-1. The resulting cleavage, between asp216 and gly217, separates the N-terminal DNA-nick sensor of PARP from its C-terminal catalytic domain. To identify the enzyme responsible for PARP inactivation in mammalian cells during apoptosis, Nicholson et al. (1995) purified the activity to homogeneity from cultured human cells of malignant cell lines with relatively high levels of this proteolytic activity. This enzyme, which they named apopain, was composed of 2 subunits of relative molecular masses 17 and 12 kD derived from a common proenzyme identified as CPP32. Nicholson et al. (1995) developed a potent peptide aldehyde inhibitor and showed that it prevented apoptotic events in vitro, suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death. Tewar ... More on the omim web site
April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600636 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed