EC 3.4.22.56 - Caspase-3

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IntEnz Enzyme Nomenclature
EC 3.4.22.56

Names

Accepted name:
caspase-3
Other names:
CPP32
apopain
yama protein
CASP-3
Systematic name:
-

Reaction

Comments:

Caspase-3 is an effector/executioner caspase, as are caspase-6 (EC 3.4.22.59) and caspase-7 (EC 3.4.22.60) [5]. These caspases are responsible for the proteolysis of the majority of cellular polypeptides, [e.g. poly(ADP-ribose) polymerase (PARP)], which leads to the apoptotic phenotype [3,5]. Procaspase-3 can be activated by caspase-1 (EC 3.4.22.36), caspase-8 (EC 3.4.22.61), caspase-9 (EC 3.4.22.62) and caspase-10 (EC 3.4.22.63) as well as by the serine protease granzyme B [1]. Caspase-3 can activate procaspase-2 (EC 3.4.22.55) [2]. Activation occurs by inter-domain cleavage followed by removal of the N-terminal prodomain [6]. While Asp-Glu-(Val/Ile)-Asp is thought to be the preferred cleavage sequence, the enzyme can accommodate different residues at P2 and P3 of the substrate [4]. Like caspase-2, a hydrophobic residue at P5 of caspase-3 leads to more efficient hydrolysis, e.g. (Val/Leu)-Asp-Val-Ala-Asp┼ is a better substrate than Asp-Val-Ala-Asp┼. This is not the case for caspase-7 [4]. 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: (13) [show] [UniProt]

References

  1. Krebs, J.F., Srinivasan, A., Wong, A.M., Tomaselli, K.J., Fritz, L.C. and Wu, J.C.
    Heavy membrane-associated caspase 3: identification, isolation, and characterization.
    Biochemistry 39: 16056-16063 (2000). [PMID: 11123933]
  2. 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]
  3. Nicholson, D. and Thornberry, N.A.
    Caspase-3 and caspase-7.
    In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds.) Handbook of Proteolytic Enzymes, 2nd ed., Elsevier, London, 2004, 1298-1302
  4. Fang, B., Boross, P.I., Tozser, J. and Weber, I.T.
    Structural and kinetic analysis of caspase-3 reveals role for S5 binding site in substrate recognition.
    J. Mol. Biol. 360: 654-666 (2006). [PMID: 16781734]
  5. 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]
  6. Martin, S.J., Amarante-Mendes, G.P., Shi, L., Chuang, T.-H., Casiano, C.A., O'Brien, G.A., Fitzgerald, P., Tan, E.M., Bokoch, G.M., Greenberg, A.H. and Green, D.R.
    The cytotoxic cell protease granzyme B initiates apoptosis in a cell-free system by proteolytic processing and activation of the ICE/CED-3 family protease, CPP32, via a novel two-step mechanism.
    EMBO J. 15: 2407-2416 (1996). [PMID: 8665848]

[EC 3.4.22.56 created 2007]