Caspase 2 also known as CASP2 is an enzyme that, in humans, is encoded by the CASP2gene.[5]CASP2orthologs[6] have been identified in nearly all mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts.
Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. The proteolytic cleavage of this protein is induced by a variety of apoptotic stimuli.[7]
Caspase 2 proteolytically cleaves other proteins. It belongs to a family of cysteine proteases called caspases that cleave proteins only at an amino acid following an aspartic acid residue. Within this family, caspase 2 is part of the Ich-1 subfamily. It is one of the most conserved caspases in different species of animal. Caspase 2 has a similar amino acid sequence to initiator caspases, including caspase 1, caspase 4, caspase 5, and caspase 9. It is produced as a zymogen, which contains a long pro-domain that is similar to that of caspase 9 and contains a protein interaction domain known as a CARD domain. Pro-caspase-2 contains two subunits, p19 and p12.
It has been shown to associate with several proteins involved in apoptosis using its CARD domain, including RIP-associated Ich-1/Ced-3-homologue protein with a death domain (RAIDD), apoptosis repressor with caspase recruitment domain (ARC), and death effector filament-forming Ced-4-like apoptosis protein (DEFCAP).[8] Together with RAIDD and p53-induced protein with a death domain ([PIDD])(LRDD), caspase 2 has been shown to form the so-called PIDDosome,[9] which may serve as an activation platform for the protease, although it may also be activated in the absence of PIDD.[10] Overall, caspase 2 appears to be a very versatile caspase with multiple functions beyond cell death induction.[11][12]
^Zhivotovsky B, Orrenius S (2005). "Caspase-2 function in response to DNA damage". Biochem. Biophys. Res. Commun. 331 (3): 859–67. doi:10.1016/j.bbrc.2005.03.191. PMID 15865942.
^ abTinel A, Tschopp J (May 2004). "The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress". Science. 304 (5672): 843–6. Bibcode:2004Sci...304..843T. doi:10.1126/science.1095432. PMID 15073321. S2CID 6583298.
^Manzl C, Krumschnabel G, Bock F, Sohm B, Labi V, Baumgartner F, Logette E, Tschopp J, Villunger A (April 2009). "Caspase-2 activation in the absence of PIDDosome formation". J. Cell Biol. 185 (2): 291–303. doi:10.1083/jcb.200811105. PMC2700374. PMID 19364921.
^Krumschnabel G, Manzl C, Villunger A (September 2009). "Caspase-2: killer, savior and safeguard--emerging versatile roles for an ill-defined caspase". Oncogene. 28 (35): 3093–6. doi:10.1038/onc.2009.173. PMC3272399. PMID 19581929.
^Krumschnabel G, Sohm B, Bock F, Manzl C, Villunger A (February 2009). "The enigma of caspase-2: the laymen's view". Cell Death Differ. 16 (2): 195–207. doi:10.1038/cdd.2008.170. PMC3272397. PMID 19023332.
^ abGuo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES (April 2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. 277 (16): 13430–7. doi:10.1074/jbc.M108029200. PMID 11832478.
^Paroni G, Henderson C, Schneider C, Brancolini C (June 2001). "Caspase-2-induced apoptosis is dependent on caspase-9, but its processing during UV- or tumor necrosis factor-dependent cell death requires caspase-3". J. Biol. Chem. 276 (24): 21907–15. doi:10.1074/jbc.M011565200. PMID 11399776.
^Droin N, Beauchemin M, Solary E, Bertrand R (December 2000). "Identification of a caspase-2 isoform that behaves as an endogenous inhibitor of the caspase cascade". Cancer Res. 60 (24): 7039–47. PMID 11156409.
^Duan H, Dixit VM (January 1997). "RAIDD is a new 'death' adaptor molecule" (PDF). Nature. 385 (6611): 86–9. Bibcode:1997Natur.385...86D. doi:10.1038/385086a0. hdl:2027.42/62739. PMID 8985253. S2CID 4317538.
^Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES (December 1996). "Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14486–91. Bibcode:1996PNAS...9314486S. doi:10.1073/pnas.93.25.14486. PMC26159. PMID 8962078.
caspase, also, known, casp2, enzyme, that, humans, encoded, casp2, gene, casp2, orthologs, have, been, identified, nearly, mammals, which, complete, genome, data, available, unique, orthologs, also, present, birds, lizards, lissamphibians, teleosts, casp2avail. Caspase 2 also known as CASP2 is an enzyme that in humans is encoded by the CASP2 gene 5 CASP2 orthologs 6 have been identified in nearly all mammals for which complete genome data are available Unique orthologs are also present in birds lizards lissamphibians and teleosts CASP2Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes1PYO 2P2C 3R5J 3R6G 3R6L 3R7B 3R7N 3R7S 3RJMIdentifiersAliasesCASP2 CASP 2 ICH1 NEDD 2 NEDD2 PPP1R57 caspase 2External IDsOMIM 600639 MGI 97295 HomoloGene 7254 GeneCards CASP2Gene location Human Chr Chromosome 7 human 1 Band7q34Start143 288 215 bp 1 End143 307 696 bp 1 Gene location Mouse Chr Chromosome 6 mouse 2 Band6 B2 1 6 20 54 cMStart42 241 919 bp 2 End42 259 442 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inspongy bonethymusganglionic eminencebloodoral cavitysecondary oocyteinternal globus palliduslactiferous ductvulvanippleTop expressed insacculeotic placodeendocardial cushionmaxillary prominencethymushair folliclemucous cell of stomachpyloric antrumsomiteabdominal wallMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functioncysteine type peptidase activity protein domain specific binding peptidase activity protein binding enzyme binding hydrolase activity identical protein binding cysteine type endopeptidase activity involved in apoptotic process cysteine type endopeptidase activity cysteine type endopeptidase activity involved in execution phase of apoptosisCellular componentcytoplasm cytosol membrane mitochondrion nucleusBiological processDNA damage response signal transduction by p53 class mediator resulting in cell cycle arrest execution phase of apoptosis protein processing human ageing positive regulation of apoptotic signaling pathway luteolysis cellular response to mechanical stimulus positive regulation of neuron apoptotic process brain development intrinsic apoptotic signaling pathway in response to DNA damage extrinsic apoptotic signaling pathway in absence of ligand positive regulation of apoptotic process ectopic germ cell programmed cell death apoptotic signaling pathway neural retina development apoptotic process regulation of apoptotic process proteolysis negative regulation of apoptotic processSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez83512366EnsemblENSG00000106144ENSMUSG00000029863UniProtP42575P29594RefSeq mRNA NM 032983NM 001224NM 032982NM 032984NM 007610RefSeq protein NP 001215NP 116764NP 116765NP 031636Location UCSC Chr 7 143 29 143 31 MbChr 6 42 24 42 26 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Interactions 3 See also 4 References 5 External linksFunction editSequential activation of caspases plays a central role in the execution phase of cell apoptosis Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits large and small that dimerize to form the active enzyme The proteolytic cleavage of this protein is induced by a variety of apoptotic stimuli 7 Caspase 2 proteolytically cleaves other proteins It belongs to a family of cysteine proteases called caspases that cleave proteins only at an amino acid following an aspartic acid residue Within this family caspase 2 is part of the Ich 1 subfamily It is one of the most conserved caspases in different species of animal Caspase 2 has a similar amino acid sequence to initiator caspases including caspase 1 caspase 4 caspase 5 and caspase 9 It is produced as a zymogen which contains a long pro domain that is similar to that of caspase 9 and contains a protein interaction domain known as a CARD domain Pro caspase 2 contains two subunits p19 and p12 It has been shown to associate with several proteins involved in apoptosis using its CARD domain including RIP associated Ich 1 Ced 3 homologue protein with a death domain RAIDD apoptosis repressor with caspase recruitment domain ARC and death effector filament forming Ced 4 like apoptosis protein DEFCAP 8 Together with RAIDD and p53 induced protein with a death domain PIDD LRDD caspase 2 has been shown to form the so called PIDDosome 9 which may serve as an activation platform for the protease although it may also be activated in the absence of PIDD 10 Overall caspase 2 appears to be a very versatile caspase with multiple functions beyond cell death induction 11 12 Interactions editCaspase 2 has been shown to interact with BH3 interacting domain death agonist 13 14 CRADD 9 15 16 and Caspase 8 13 17 See also editThe Proteolysis Map CaspaseReferences edit a b c GRCh38 Ensembl release 89 ENSG00000106144 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000029863 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Kumar S White DL Takai S Turczynowicz S Juttner CA Hughes TP June 1995 Apoptosis regulatory gene NEDD2 maps to human chromosome segment 7q34 35 a region frequently affected in haematological neoplasms Hum Genet 95 6 641 4 doi 10 1007 bf00209480 PMID 7789948 S2CID 22813779 OrthoMaM phylogenetic marker CASP2 coding sequence Archived from the original on 24 September 2015 Retrieved 20 December 2009 Entrez Gene CASP2 Zhivotovsky B Orrenius S 2005 Caspase 2 function in response to DNA damage Biochem Biophys Res Commun 331 3 859 67 doi 10 1016 j bbrc 2005 03 191 PMID 15865942 a b Tinel A Tschopp J May 2004 The PIDDosome a protein complex implicated in activation of caspase 2 in response to genotoxic stress Science 304 5672 843 6 Bibcode 2004Sci 304 843T doi 10 1126 science 1095432 PMID 15073321 S2CID 6583298 Manzl C Krumschnabel G Bock F Sohm B Labi V Baumgartner F Logette E Tschopp J Villunger A April 2009 Caspase 2 activation in the absence of PIDDosome formation J Cell Biol 185 2 291 303 doi 10 1083 jcb 200811105 PMC 2700374 PMID 19364921 Krumschnabel G Manzl C Villunger A September 2009 Caspase 2 killer savior and safeguard emerging versatile roles for an ill defined caspase Oncogene 28 35 3093 6 doi 10 1038 onc 2009 173 PMC 3272399 PMID 19581929 Krumschnabel G Sohm B Bock F Manzl C Villunger A February 2009 The enigma of caspase 2 the laymen s view Cell Death Differ 16 2 195 207 doi 10 1038 cdd 2008 170 PMC 3272397 PMID 19023332 a b Guo Y Srinivasula SM Druilhe A Fernandes Alnemri T Alnemri ES April 2002 Caspase 2 induces apoptosis by releasing proapoptotic proteins from mitochondria J Biol Chem 277 16 13430 7 doi 10 1074 jbc M108029200 PMID 11832478 Paroni G Henderson C Schneider C Brancolini C June 2001 Caspase 2 induced apoptosis is dependent on caspase 9 but its processing during UV or tumor necrosis factor dependent cell death requires caspase 3 J Biol Chem 276 24 21907 15 doi 10 1074 jbc M011565200 PMID 11399776 Droin N Beauchemin M Solary E Bertrand R December 2000 Identification of a caspase 2 isoform that behaves as an endogenous inhibitor of the caspase cascade Cancer Res 60 24 7039 47 PMID 11156409 Duan H Dixit VM January 1997 RAIDD is a new death adaptor molecule PDF Nature 385 6611 86 9 Bibcode 1997Natur 385 86D doi 10 1038 385086a0 hdl 2027 42 62739 PMID 8985253 S2CID 4317538 Srinivasula SM Ahmad M Fernandes Alnemri T Litwack G Alnemri ES December 1996 Molecular ordering of the Fas apoptotic pathway the Fas APO 1 protease Mch5 is a CrmA inhibitable protease that activates multiple Ced 3 ICE like cysteine proteases Proc Natl Acad Sci U S A 93 25 14486 91 Bibcode 1996PNAS 9314486S doi 10 1073 pnas 93 25 14486 PMC 26159 PMID 8962078 External links editThe MEROPS online database for peptidases and their inhibitors C14 006 permanent dead link Overview of all the structural information available in the PDB for UniProt P42575 Human Caspase 2 at the PDBe KB This article incorporates text from the United States National Library of Medicine which is in the public domain Portal nbsp Biology 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