EC 3.4.22.55 - Caspase-2

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IntEnz Enzyme Nomenclature
EC 3.4.22.55

Names

Accepted name:
caspase-2
Other names:
ICH-1
NEDD-2
caspase-2L
caspase-2S
neural precursor cell expressed developmentally down-regulated protein 2
CASP-2
NEDD2 protein
Systematic name:
-

Reaction

Comments:

Caspase-2 is an initiator caspase, as are caspase-8 (EC 3.4.22.61), caspase-9 (EC 3.4.22.62) and caspase-10 (EC 3.4.22.63) [6]. Contains a caspase-recruitment domain (CARD) in its N-terminal prodomain, which plays a role in procaspase activation [6]. Two forms of caspase-2 exist that have antagonistic effects: caspase-2L induces programmed cell death and caspase-2S suppresses cell death [2,3,5]. Caspase-2 is activated by caspase-3 (EC 3.4.22.56), or by a caspase-3-like protease. Activation involves cleavage of the N-terminal prodomain, followed by self-proteolysis between the large and small subunits of pro-caspase-2 and further proteolysis into smaller fragments [3]. Proteolysis occurs at Asp residues and the preferred substrate for this enzyme is a pentapeptide rather than a tetrapeptide [5]. Apart from itself, the enzyme can cleave golgin-16, which is present in the Golgi complex and has a cleavage site that is unique for caspase-2 [4,5]. αII-Spectrin, a component of the membrane cytoskeleton, is a substrate of the large isoform of pro-caspase-2 (caspase-2L) but not of the short isoform (caspase-2S). Belongs in peptidase family C14.

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , MEROPS , UniPathway
Protein domains and families: PROSITE:PDOC00864
Structural data: CSA , EC2PDB
UniProtKB/Swiss-Prot:

References

  1. Kumar, S., Kinoshita, M., Noda, M., Copeland, N.G. and Jenkins, N.A.
    Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1 β-converting enzyme.
    Genes Dev. 8: 1613-1626 (1994). [PMID: 7958843]
  2. Wang, L., Miura, M., Bergeron, L., Zhu, H. and Yuan, J.
    Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death.
    Cell 78: 739-750 (1994). [PMID: 8087842]
  3. Li, H., Bergeron, L., Cryns, V., Pasternack, M.S., Zhu, H., Shi, L., Greenberg, A. and Yuan, J.
    Activation of caspase-2 in apoptosis.
    J. Biol. Chem. 272: 21010-21017 (1997). [PMID: 9261102]
  4. Mancini, M., Machamer, C.E., Roy, S., Nicholson, D.W., Thornberry, N.A., Casciola-Rosen, L.A. and Rosen, A.
    Caspase-2 is localized at the Golgi complex and cleaves golgin-160 during apoptosis.
    J. Cell Biol. 149: 603-612 (2000). [PMID: 10791974]
  5. Zhivotovsky, B. and Orrenius, S.
    Caspase-2 function in response to DNA damage.
    Biochem. Biophys. Res. Commun. 331: 859-867 (2005). [PMID: 15865942]
  6. Chang, H.Y. and Yang, X.
    Proteases for cell suicide: functions and regulation of caspases.
    Microbiol. Mol. Biol. Rev. 64: 821-846 (2000). [PMID: 11104820]

[EC 3.4.22.55 created 2007]