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Caspase 2, apoptosis-related cysteine peptidase (neural precursor cell expressed, developmentally down-regulated 2)
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| PDB rendering based on 1pyo. | ||||||||||||||
| Available structures: 1pyo, 2p2c | ||||||||||||||
| Identifiers | ||||||||||||||
| Symbols | CASP2; CASP-2; ICH-1L; ICH-1L/1S; ICH1; NEDD2 | |||||||||||||
| External IDs | OMIM: 600639 MGI: 97295 HomoloGene: 7254 | |||||||||||||
| EC number | 3.4.22.55 | |||||||||||||
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| RNA expression pattern | ||||||||||||||
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| Orthologs | ||||||||||||||
| Human | Mouse | |||||||||||||
| Entrez | 835 | 12366 | ||||||||||||
| Ensembl | ENSG00000106144 | ENSMUSG00000029863 | ||||||||||||
| Uniprot | P42575 | P29594 | ||||||||||||
| Refseq | NM_032982 (mRNA) NP_116764 (protein) |
NM_007610 (mRNA) NP_031636 (protein) |
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| Location | Chr 7: 142.7 - 142.71 Mb | Chr 6: 42.19 - 42.21 Mb | ||||||||||||
| Pubmed search | [1] | [2] | ||||||||||||
Caspase 2 also known as CASP2 is an enzyme which in humans is encoded by the CASP2 gene.[1]
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Function
Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which 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.[2]
Caspase 2 proteolytically cleaves other proteins. It belongs to a family of cysteine proteases called caspases that only cleave proteins at an amino acid following a 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).[3] Together with RAIDD and p53-induced protein with a death domain ([PIDD])(LRDD) caspase 2 has been shown to form the so called PIDDosome,[4] which may serve as an activation platform for the protease, although it may also be activated in the absence of PIDD.[5] In addition, caspase 2 may form a complex with the catalytic subunit of DNA-PK (DNA-PKcs) and PIDD (LRDD), which is involved in DNA repair after DNA damage.[6] Overall, caspase 2 appears to be a very versatile caspase with multiple functions beyond cell death induction.[7][8]
Interactions
Caspase 2 has been shown to interact with CRADD,[4][9][10] Caspase 8[11][12] and BH3 interacting domain death agonist.[13][11]
See also
References
- ^ 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. PMID 7789948.
- ^ "Entrez Gene: CASP2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=835.
- ^ Zhivotovsky B, Orrenius S (2005). "Caspase-2 function in response to DNA damage". Biochem. Biophys. Res. Commun. 331 (3): 859–67. doi:. PMID 15865942.
- ^ a b Tinel, Antoine; Tschopp Jürg (May. 2004). "The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress". Science (United States) 304 (5672): 843-6. doi:. PMID 15073321.
- ^ 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:. PMID 19364921.
- ^ Shi M, Vivian CJ, Lee KJ, Ge C, Morotomi-Yano K, Manzl C, Bock F, Sato S, Tomomori-Sato C, Zhu R, Haug JS, Swanson SK, Washburn MP, Chen DJ, Chen BP, Villunger A, Florens L, Du C (February 2009). "DNA-PKcs-PIDDosome: a nuclear caspase-2-activating complex with role in G2/M checkpoint maintenance". Cell 136 (3): 508–20. doi:. PMID 19203584.
- ^ 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:. 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:. PMID 19023332.
- ^ Droin, N; Beauchemin M, Solary E, Bertrand R (Dec. 2000). "Identification of a caspase-2 isoform that behaves as an endogenous inhibitor of the caspase cascade". Cancer Res. (United States) 60 (24): 7039-47. ISSN 0008-5472. PMID 11156409.
- ^ Duan, H; Dixit V M (Jan. 1997). "RAIDD is a new 'death' adaptor molecule". Nature (ENGLAND) 385 (6611): 86-9. doi:. ISSN 0028-0836. PMID 8985253.
- ^ a b Guo, Yin; Srinivasula Srinivasa M, Druilhe Anne, Fernandes-Alnemri Teresa, Alnemri Emad S (Apr. 2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. (United States) 277 (16): 13430-7. doi:. ISSN 0021-9258. PMID 11832478.
- ^ Srinivasula, S M; Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri E S (Dec. 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. (UNITED STATES) 93 (25): 14486-91. ISSN 0027-8424. PMID 8962078.
- ^ Paroni, G; Henderson C, Schneider C, Brancolini C (Jun. 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. (United States) 276 (24): 21907-15. doi:. ISSN 0021-9258. PMID 11399776.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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