KEGG   ENZYME: 3.4.22.55Help
Entry
EC 3.4.22.55                Enzyme                                 

Name
caspase-2;
ICH-1;
NEDD-2;
caspase-2L;
caspase-2S;
neural precursor cell expressed developmentally down-regulated protein 2;
CASP-2;
NEDD2 protein
Class
Hydrolases;
Acting on peptide bonds (peptidases);
Cysteine endopeptidases
BRITE hierarchy
Reaction(IUBMB)
Strict requirement for an Asp residue at P1, with Asp316 being essential for proteolytic activity and has a preferred cleavage sequence of Val-Asp-Val-Ala-Asp!
Comment
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 with antagonistic effects exist: 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]. alphaII-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.
History
EC 3.4.22.55 created 2007
Orthology
K02186  
caspase 2
Genes
HSA: 
835(CASP2)
PTR: 
463804(CASP2)
PPS: 
100984572(CASP2)
GGO: 
101128958(CASP2)
PON: 
100454928(CASP2)
NLE: 
100599260(CASP2)
MCC: 
704339(CASP2)
MCF: 
102128712(CASP2)
RRO: 
104674919(CASP2)
CJC: 
100402493(CASP2)
MMU: 
12366(Casp2)
RNO: 
64314(Casp2)
CGE: 
100689445(Casp2)
NGI: 
103730398(Casp2)
HGL: 
101712106(Casp2)
OCU: 
100101590(CASP2)
TUP: 
102498970(CASP2)
CFA: 
482737(CASP2)
AML: 
100474060(CASP2)
UMR: 
103668980(CASP2)
FCA: 
101088318(CASP2)
PTG: 
102948856(CASP2)
BTA: 
531419(CASP2)
BOM: 
102272786(CASP2)
PHD: 
102317813(CASP2)
CHX: 
102183569(CASP2)
OAS: 
101115025(CASP2)
SSC: 
100521118(CASP2)
CFR: 
102508934(CASP2)
BACU: 
103017857(CASP2)
LVE: 
103085195(CASP2)
ECB: 
100050611(CASP2)
MYB: 
102264102(CASP2)
MYD: 
102774985(CASP2)
PALE: 
102895485(CASP2)
MDO: 
100011923(CASP2)
SHR: 
100919881(CASP2)
OAA: 
100074924(CASP2)
GGA: 
395857(CASP2)
MGP: 
100544010(CASP2)
CJO: 
107319105(CASP2)
APLA: 
101794734(CASP2)
TGU: 
100221143(CASP2)
GFR: 
102043378(CASP2)
FAB: 
101805629(CASP2)
PHI: 
102108085(CASP2)
CCW: 
104687148(CASP2)
FPG: 
101915905(CASP2)
FCH: 
102048179(CASP2)
CLV: 
102095337(CASP2)
AAM: 
106497280(CASP2)
ASN: 
102377638(CASP2)
AMJ: 
102558644(CASP2)
PSS: 
102463164(CASP2)
CMY: 
102929343(CASP2)
ACS: 
100567806(casp2)
PBI: 
103051794(CASP2)
GJA: 
107115535(CASP2)
XLA: 
397817(casp2) 398436
XTR: 
100486813(casp2)
DRE: 
373118(casp2)
TRU: 
101072588(casp2)
MZE: 
101470507(casp2)
OLA: 
101171774(casp2)
XMA: 
102216745(casp2)
LCM: 
102349624(CASP2)
BFO: 
CIN: 
API: 
BMY: 
LOA: 
HRO: 
LGI: 
CRG: 
105318727(Caspase-6) 105322339(Caspase-2) 105340308 105343974(caspase-2)
OBI: 
SMM: 
 » show all
Taxonomy
Reference
1  [PMID:7958843]
  Authors
Kumar S, Kinoshita M, Noda M, Copeland NG, Jenkins NA.
  Title
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 beta-converting enzyme.
  Journal
Genes. Dev. 8 (1994) 1613-26.
  Sequence
[mmu:12366]
Reference
2  [PMID:8087842]
  Authors
Wang L, Miura M, Bergeron L, Zhu H, Yuan J.
  Title
Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death.
  Journal
Cell. 78 (1994) 739-50.
  Sequence
[hsa:835]
Reference
3  [PMID:9261102]
  Authors
Li H, Bergeron L, Cryns V, Pasternack MS, Zhu H, Shi L, Greenberg A, Yuan J.
  Title
Activation of caspase-2 in apoptosis.
  Journal
J. Biol. Chem. 272 (1997) 21010-7.
Reference
4  [PMID:10791974]
  Authors
Mancini M, Machamer CE, Roy S, Nicholson DW, Thornberry NA, Casciola-Rosen LA, Rosen A.
  Title
Caspase-2 is localized at the Golgi complex and cleaves golgin-160 during apoptosis.
  Journal
J. Cell. Biol. 149 (2000) 603-12.
  Sequence
[hsa:2802]
Reference
5  [PMID:15865942]
  Authors
Zhivotovsky B, Orrenius S.
  Title
Caspase-2 function in response to DNA damage.
  Journal
Biochem. Biophys. Res. Commun. 331 (2005) 859-67.
Reference
6  [PMID:11104820]
  Authors
Chang HY, Yang X.
  Title
Proteases for cell suicide: functions and regulation of caspases.
  Journal
Microbiol. Mol. Biol. Rev. 64 (2000) 821-46.
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 
CAS: 
182372-14-1

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