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: 698788(CASP6)
MCF: 101867077(CASP6)
CSAB: 103236104(CASP6)
RRO: 104671841(CASP6)
RBB: 108541015(CASP6)
CJC: 100394331(CASP6)
SBQ: 101046319(CASP6)
MMU: 12368(Casp6)
RNO: 103689977 83584(Casp6)
CGE: 100766458(Casp6)
NGI: 103742454(Casp6)
HGL: 101707090(Casp6)
CCAN: 109694926(Casp6)
OCU: 100341546(CASP6)
TUP: 102481080(CASP6)
CFA: 487899(CASP6)
AML: 100476854(CASP6)
UMR: 103661832(CASP6)
ORO: 101375690(CASP6)
FCA: 768261(PLA2G12A)
PTG: 102964120
AJU: 106983648
BTA: 538409(CASP6)
BOM: 102288095(CASP6)
BIU: 109560257(CASP6)
PHD: 102327519(CASP6)
CHX: 102184605(CASP6)
OAS: 101119820(CASP6)
SSC: 100517293(CASP6)
CFR: 102521752(CASP6)
CDK: 105089897(CASP6)
BACU: 103001713(CASP6)
LVE: 103075936(CASP6)
OOR: 101275780 101285172(CASP6)
ECB: 100072861(CASP6)
EPZ: 103562386(CASP6)
EAI: 106829803(CASP6)
MYB: 102253010(CASP6)
MYD: 102755758(CASP6)
HAI: 109379418(CASP6)
RSS: 109452780(CASP6)
PALE: 102890010(CASP6)
LAV: 100668723(CASP6)
TMU: 101347761
MDO: 100009858(CASP6) 100019753
OAA: 100074650(CASP6)
GGA: 395477(CASP6)
MGP: 100544078(CASP6)
CJO: 107313602(CASP6)
APLA: 101794069(CASP6)
ACYG: 106038643(CASP6)
TGU: 100232257(CASP6)
GFR: 102034936(CASP6)
FAB: 101808850(CASP6)
PHI: 102111062(CASP6)
PMAJ: 107203274(CASP6)
CCW: 104697124(CASP6)
FPG: 101917586(CASP6)
FCH: 102049956(CASP6)
CLV: 102092805(CASP6)
EGZ: 104135531(CASP6)
AAM: 106492034(CASP6)
ASN: 102387853(CASP6)
AMJ: 102572507(CASP6)
PSS: 102455131(CASP6)
CMY: 102945769(CASP6)
CPIC: 101932940(CASP6)
ACS: 100564002(casp6)
PVT: 110087283(CASP6)
PBI: 103055774(CASP6)
GJA: 107123241(CASP6)
XLA: 397818(casp6.L)
XTR: 496478(casp6)
NPR: 108798289(CASP6)
DRE: 552927(casp6)
TRU: 101075398(casp6)
LCO: 104927260(casp6)
NCC: 104941008(casp6)
OLA: 101157998 101164455(casp6)
XMA: 102225519(casp6)
PRET: 103472834(casp6)
NFU: 107375324(casp6)
CSEM: 103383854(casp6)
LCF: 108888249(casp6)
HCQ: 109511079(casp6)
BPEC: 110165342(casp6)
ELS: 105020987(casp6)
SFM: 108936646(casp6) 108936647
LCM: 102356934(CASP6)
CMK: 103189377(casp6)
CIN: 100183628
SPU: 584221
APLC: 110990159
SKO: 100368637
TCA: 100142180
 » 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 9:1046-56 (2002)
DOI:10.1038/sj.cdd.4401065
Reference
2  [PMID:11104820]
  Authors
Chang HY, Yang X.
  Title
Proteases for cell suicide: functions and regulation of caspases.
  Journal
Microbiol Mol Biol Rev 64:821-46 (2000)
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 364:629-34 (2002)
DOI:10.1042/BJ20011787
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 6:2386-94 (2006)
DOI:10.1002/pmic.200500366
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 99:9492-7 (2002)
DOI:10.1073/pnas.132241599
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 93:8395-400 (1996)
DOI:10.1073/pnas.93.16.8395
Other DBs
ExplorEnz - The Enzyme Database: 3.4.22.59
IUBMB Enzyme Nomenclature: 3.4.22.59
ExPASy - ENZYME nomenclature database: 3.4.22.59
BRENDA, the Enzyme Database: 3.4.22.59
CAS: 182372-15-2

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