Caspase 2

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.{{cite web | title = Entrez Gene: CASP2 | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=835}}

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).{{cite journal | vauthors = Zhivotovsky B, Orrenius S | title = Caspase-2 function in response to DNA damage | journal = Biochem. Biophys. Res. Commun. | volume = 331 | issue = 3 | pages = 859–67 | year = 2005 | pmid = 15865942 | doi = 10.1016/j.bbrc.2005.03.191 | doi-access = free }} Together with RAIDD and p53-induced protein with a death domain ([PIDD])(LRDD), caspase 2 has been shown to form the so-called PIDDosome,{{cite journal | vauthors = Tinel A, Tschopp J | title = The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress | journal = Science | volume = 304 | issue = 5672 | pages = 843–6 | date = May 2004 | pmid = 15073321 | doi = 10.1126/science.1095432 | bibcode = 2004Sci...304..843T | s2cid = 6583298 }} which may serve as an activation platform for the protease, although it may also be activated in the absence of PIDD.{{cite journal | vauthors = Manzl C, Krumschnabel G, Bock F, Sohm B, Labi V, Baumgartner F, Logette E, Tschopp J, Villunger A | title = Caspase-2 activation in the absence of PIDDosome formation | journal = J. Cell Biol. | volume = 185 | issue = 2 | pages = 291–303 | date = April 2009 | pmid = 19364921 | pmc = 2700374 | doi = 10.1083/jcb.200811105 | url = https://serval.unil.ch/resource/serval:BIB_ED9C5C0DC6DE.P001/REF }} Overall, caspase 2 appears to be a very versatile caspase with multiple functions beyond cell death induction.{{cite journal | vauthors = Krumschnabel G, Manzl C, Villunger A | title = Caspase-2: killer, savior and safeguard--emerging versatile roles for an ill-defined caspase | journal = Oncogene | volume = 28 | issue = 35 | pages = 3093–6 | date = September 2009 | pmid = 19581929 | pmc = 3272399 | doi = 10.1038/onc.2009.173 }}{{cite journal | vauthors = Krumschnabel G, Sohm B, Bock F, Manzl C, Villunger A | title = The enigma of caspase-2: the laymen's view | journal = Cell Death Differ. | volume = 16 | issue = 2 | pages = 195–207 | date = February 2009 | pmid = 19023332 | pmc = 3272397 | doi = 10.1038/cdd.2008.170 }}

Caspase 2 has been shown to interact with:

• BH3 interacting domain death agonist,{{cite journal | vauthors = Paroni G, Henderson C, Schneider C, Brancolini C | title = Caspase-2-induced apoptosis is dependent on caspase-9, but its processing during UV- or tumor necrosis factor-dependent cell death requires caspase-3 | journal = J. Biol. Chem. | volume = 276 | issue = 24 | pages = 21907–15 | date = June 2001 | pmid = 11399776 | doi = 10.1074/jbc.M011565200 | doi-access = free }}
• CRADD,{{cite journal | vauthors = Droin N, Beauchemin M, Solary E, Bertrand R | title = Identification of a caspase-2 isoform that behaves as an endogenous inhibitor of the caspase cascade | journal = Cancer Res. | volume = 60 | issue = 24 | pages = 7039–47 | date = December 2000 | pmid = 11156409 }}{{cite journal | vauthors = Duan H, Dixit VM | title = RAIDD is a new 'death' adaptor molecule | journal = Nature | volume = 385 | issue = 6611 | pages = 86–9 | date = January 1997 | pmid = 8985253 | doi = 10.1038/385086a0 | bibcode = 1997Natur.385...86D | hdl = 2027.42/62739 | s2cid = 4317538 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/62739/1/385086a0.pdf | hdl-access = free }} and
• Caspase 8.{{cite journal | vauthors = Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES | title = Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria | journal = J. Biol. Chem. | volume = 277 | issue = 16 | pages = 13430–7 | date = April 2002 | pmid = 11832478 | doi = 10.1074/jbc.M108029200 | doi-access = free }}{{cite journal | vauthors = Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES | title = 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 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 25 | pages = 14486–91 | date = December 1996 | pmid = 8962078 | pmc = 26159 | doi = 10.1073/pnas.93.25.14486| bibcode = 1996PNAS...9314486S | doi-access = free }}

• The Proteolysis Map
• Caspase

{{reflist}}

• The MEROPS online database for peptidases and their inhibitors: [https://archive.today/20121223140546/http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=C14.006 C14.006]
• {{PDBe-KB2|P42575|Human Caspase-2}}

{{NLM content}}

{{Cysteine proteases}}

{{Enzymes}}

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Category:EC 3.4.22

Category:Caspases