KEGG   ENZYME: 3.4.22.61Help
Entry
EC 3.4.22.61                Enzyme                                 

Name
caspase-8;
FLICE, FADD-like ICE;
MACH;
MORT1-associated CED-3 homolog;
Mch5;
mammalian Ced-3 homolog 5;
CASP-8;
ICE-like apoptotic protease 5;
FADD-homologous ICE/CED-3-like protease;
apoptotic cysteine protease;
apoptotic protease Mch-5;
CAP4
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 (Leu/Asp/Val)-Glu-Thr-Asp!(Gly/Ser/Ala)
Comment
Caspase-8 is an initiator caspase, as are caspase-2 (EC 3.4.22.55), caspase-9 (EC 3.4.22.62) and caspase-10 (EC 3.4.22.63) [1]. Caspase-8 is the apical activator of the extrinsic (death receptor) apoptosis pathway, triggered by death receptor ligation [2]. It contains two tandem death effector domains (DEDs) in its N-terminal prodomain, and these play a role in procaspase activation [1]. This enzyme is linked to cell surface death receptors such as Fas [1,5]. When Fas is aggregated by the Fas ligand, procaspase-8 is recruited to the death receptor where it is activated [1]. The enzyme has a preference for Glu at P3 and prefers small residues, such as Gly, Ser and Ala, at the P1' position. It has very broad P4 specificity, tolerating substrates with Asp, Val or Leu in this position [2,3,4]. Endogenous substrates for caspase-8 include procaspase-3, the pro-apoptotic Bcl-2 family member Bid, RIP, PAK2 and the caspase-8 activity modulator FLIPL [4,5]. Belongs in peptidase family C14.
History
EC 3.4.22.61 created 2007
Orthology
K04398  caspase 8
Genes
HSA: 841(CASP8)
PTR: 746477(CASP8)
PPS: 100978497(CASP8)
GGO: 101138898(CASP8)
PON: 100172115(CASP8)
NLE: 100586183(CASP8)
MCC: 702781(CASP8)
MCF: 101865354(CASP8)
CSAB: 103217637(CASP8)
RRO: 104671864(CASP8)
RBB: 108532002(CASP8)
CJC: 100395220(CASP8)
SBQ: 101053601(CASP8)
MMU: 12370(Casp8)
RNO: 64044(Casp8)
CGE: 100689369(Casp8)
NGI: 103738672(Casp8)
HGL: 101702773(Casp8)
CCAN: 109689613(Casp8)
OCU: 100348477(CASP8)
TUP: 102498355(CASP8)
CFA: 488473(CASP8)
AML: 100472842(CASP8)
UMR: 103659742(CASP8)
ORO: 101365855(CASP8)
FCA: 100142684(CASP8)
PTG: 102962460(CASP8)
AJU: 106987995(CASP8)
BTA: 507481(CASP8)
BOM: 102272602(CASP8)
BIU: 109569521(CASP8)
PHD: 102326267(CASP8)
CHX: 102169919(CASP8)
OAS: 101107334(CASP8)
SSC: 595105(CASP8)
CFR: 102508224(CASP8)
CDK: 105099181(CASP8)
BACU: 103004642(CASP8)
LVE: 103077054(CASP8)
OOR: 101281780(CASP8)
ECB: 100066502(CASP8)
EPZ: 103565685(CASP8)
EAI: 106823493(CASP8)
MYB: 102246377(CASP8)
MYD: 102761550(CASP8)
HAI: 109379228(CASP8)
RSS: 109444985(CASP8)
PALE: 102878181(CASP8)
LAV: 100660542(CASP8) 100663575
TMU: 101344302
MDO: 100017025(CASP18) 100617599(CASP8)
SHR: 100931580
OAA: 100082949(CASP8) 100087835
GGA: 395284(CASP8)
MGP: 100541513(CASP8) 100541666
APLA: 101803161(CASP8) 106014283
TGU: 100222284
PHI: 102110759
PMAJ: 107207226
CCAE: 111931990
CCW: 104693779
FPG: 101916968(CASP8) 106113022
FCH: 102056597(CASP8) 106630990
EGZ: 104130511(CASP8)
AAM: 106492412 106492473(CASP8)
AMJ: 102573591(CASP8) 102575862(CASP18)
CPIC: 101934006(CASP8) 101934828
XLA: 373559(casp8.L)
XTR: 100495471(casp8)
NPR: 108795080
DRE: 557302(casp8l2) 58022(casp8)
TRU: 101075191 101075631(casp8)
OLA: 100049400(casp8) 100125536
XMA: 111608841
LCF: 108883888
SDU: 111229030(casp8)
BPEC: 110173494(casp8) 110173519
SASA: 106569473
CMK: 103171902(casp8)
CIN: 100183123(casp8)
SPU: 585496
APLC: 110986601
DME: Dmel_CG7486(Dredd)
DER: 6555550
DSI: Dsimw501_GD16467(Dsim_Dredd)
DWI: 6644580
DYA: Dyak_GE16575(Dyak_Dredd)
MDE: 101900122
AGA: AgaP_AGAP011693(CASPL1)
AAG: 5563818
AME: 724930
BIM: 100741190
BTER: 100652115
SOC: 105205440
AEC: 105147270
ACEP: 105625685
PBAR: 105429159
HST: 105190451
DQU: 106743797
CFO: 105248277
LHU: 105678455
PGC: 109856665
PCF: 106791240
NVI: 100680000
MDL: 103579887
TCA: 661095(Dredd)
DPA: 109534720
NVL: 108556913
BMOR: 100141428(Dredd)
PMAC: 106720189
PRAP: 110996855
HAW: 110369675
PXY: 105390324
CLEC: 106661122
ZNE: 110835030
SHX: MS3_10084
EPA: 110231936
HMG: 100207763 100579132(casp8)
 » show all
Taxonomy
Reference
1  [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
2  [PMID:8681376]
  Authors
Boldin MP, Goncharov TM, Goltsev YV, Wallach D.
  Title
Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death.
  Journal
Cell 85:803-15 (1996)
DOI:10.1016/S0092-8674(00)81265-9
  Sequence
[hsa:841]
Reference
3  [PMID:8681377]
  Authors
Muzio M, Chinnaiyan AM, Kischkel FC, O'Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME, Dixit VM.
  Title
FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex.
  Journal
Cell 85:817-27 (1996)
DOI:10.1016/S0092-8674(00)81266-0
  Sequence
[hsa:841]
Reference
4
  Authors
Salvesen, G.S. and Boatright, K.M.
  Title
Caspase-8.
  Journal
In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds.), Handbook of Proteolytic Enzymes, 2nd ed., Elsevier, London, 2004, p. 1293-1296.
Reference
5  [PMID:16186808]
  Authors
Fischer U, Stroh C, Schulze-Osthoff K.
  Title
Unique and overlapping substrate specificities of caspase-8 and caspase-10.
  Journal
Oncogene 25:152-9 (2006)
DOI:10.1038/sj.onc.1209015
Reference
6  [PMID:10964557]
  Authors
Blanchard H, Donepudi M, Tschopp M, Kodandapani L, Wu JC, Grutter MG.
  Title
Caspase-8 specificity probed at subsite S(4): crystal structure of the caspase-8-Z-DEVD-cho complex.
  Journal
J Mol Biol 302:9-16 (2000)
DOI:10.1006/jmbi.2000.4041
Reference
7  [PMID:15209560]
  Authors
Boatright KM, Deis C, Denault JB, Sutherlin DP, Salvesen GS.
  Title
Activation of caspases-8 and -10 by FLIP(L).
  Journal
Biochem J 382:651-7 (2004)
DOI:10.1042/BJ20040809
Other DBs
ExplorEnz - The Enzyme Database: 3.4.22.61
IUBMB Enzyme Nomenclature: 3.4.22.61
ExPASy - ENZYME nomenclature database: 3.4.22.61
BRENDA, the Enzyme Database: 3.4.22.61
CAS: 179241-78-2

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