KEGG   ENZYME: 3.4.22.59Help
Entry
EC 3.4.22.59                Enzyme                                 

Name
caspase-6;
CASP-6;
apoptotic protease Mch-2;
Mch2
Class
Hydrolases;
Acting on peptide bonds (peptidases);
Cysteine endopeptidases
BRITE hierarchy
Reaction(IUBMB)
Strict requirement for Asp at position P1 and has a preferred cleavage sequence of Val-Glu-His-Asp!
Comment
Caspase-6 is an effector/executioner caspase, as are caspase-3 (EC 3.4.22.56) and caspase-7 (EC 3.4.22.60) [2]. 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 [2]. Caspase-6 can cleave its prodomain to produce mature caspase-6, which directly activates caspase-8 (EC 3.4.22.61) and leads to the release of cytochrome c from the mitochondria. The release of cytochrome c is an essential component of the intrinsic apoptosis pathway [1]. The enzyme can also cleave and inactivate lamins, the intermediate filament scaffold proteins of the nuclear envelope, leading to nuclear fragmentation in the final phases of apoptosis [2,4,5,6]. Belongs in peptidase family C14.
History
EC 3.4.22.59 created 2007
Orthology
K04396  
caspase 6
Genes
HSA: 
839(CASP6)
PTR: 
736606(CASP6)
PPS: 
100973393(CASP6)
GGO: 
101149243(CASP6)
PON: 
100450330(CASP6)
NLE: 
100591774(CASP6)
MCC: 
MCF: 
CJC: 
100394331(CASP6)
MMU: 
12368(Casp6)
RNO: 
83584(Casp6)
CGE: 
100766458(Casp6)
HGL: 
101707090(Casp6)
TUP: 
102481080(CASP6)
CFA: 
487899(CASP6)
AML: 
UMR: 
103661832(CASP6)
FCA: 
768261(CASP6)
PTG: 
BTA: 
538409(CASP6)
BOM: 
102288095(CASP6)
PHD: 
102327519(CASP6)
CHX: 
102184605(CASP6)
OAS: 
101119820(CASP6)
SSC: 
100517293(CASP6)
CFR: 
102521752(CASP6)
BACU: 
103001713(CASP6)
LVE: 
103075936(CASP6)
ECB: 
100072861(CASP6)
MYB: 
102253010(CASP6)
MYD: 
102755758(CASP6)
PALE: 
102890010(CASP6)
MDO: 
100009858(CASP6)
SHR: 
100930545(CASP6)
OAA: 
100074650(CASP6)
GGA: 
395477(CASP6)
MGP: 
APLA: 
101794069(CASP6)
TGU: 
100232257(CASP6)
FAB: 
101808850(CASP6)
PHI: 
102111062(CASP6)
FPG: 
101917586(CASP6)
FCH: 
102049956(CASP6)
CLV: 
102092805(CASP6)
ASN: 
102387853(CASP6)
AMJ: 
102572507(CASP6)
PSS: 
102455131(CASP6)
CMY: 
102945769(CASP6)
ACS: 
100564002(casp6)
PBI: 
103055774(CASP6)
XLA: 
397818(casp6)
XTR: 
496478(casp6)
DRE: 
552927(casp6)
TRU: 
MZE: 
OLA: 
XMA: 
LCM: 
102356934(CASP6)
CMK: 
103189377(casp6)
BFO: 
CIN: 
SPU: 
TCA: 
 » show all
Taxonomy
Reference
1  [PMID:12232792]
  Authors
Cowling V, Downward J.
  Title
Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis pathway: absolute requirement for removal of caspase-6 prodomain.
  Journal
Cell. Death. Differ. 9 (2002) 1046-56.
Reference
2  [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.
Reference
3  [PMID:12049625]
  Authors
Kang BH, Ko E, Kwon OK, Choi KY.
  Title
The structure of procaspase 6 is similar to that of active mature caspase 6.
  Journal
Biochem. J. 364 (2002) 629-34.
Reference
4  [PMID:16518869]
  Authors
Lee SC, Chan J, Clement MV, Pervaiz S.
  Title
Functional proteomics of resveratrol-induced colon cancer cell apoptosis: caspase-6-mediated cleavage of lamin A is a major signaling loop.
  Journal
Proteomics. 6 (2006) 2386-94.
Reference
5  [PMID:12089322]
  Authors
MacLachlan TK, El-Deiry WS.
  Title
Apoptotic threshold is lowered by p53 transactivation of caspase-6.
  Journal
Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 9492-7.
Reference
6  [PMID:8710882]
  Authors
Takahashi A, Alnemri ES, Lazebnik YA, Fernandes-Alnemri T, Litwack G, Moir RD, Goldman RD, Poirier GG, Kaufmann SH, Earnshaw WC.
  Title
Cleavage of lamin A by Mch2 alpha but not CPP32: multiple interleukin 1 beta-converting enzyme-related proteases with distinct substrate recognition properties are active in apoptosis.
  Journal
Proc. Natl. Acad. Sci. U. S. A. 93 (1996) 8395-400.
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 
CAS: 
182372-15-2

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