KEGG   ENZYME: 3.4.22.61
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
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
HSA841(CASP8)
PTR746477(CASP8)
PPS100978497(CASP8)
GGO101138898(CASP8)
PON100172115(CASP8)
NLE100586183(CASP8)
MCC702781(CASP8)
MCF101865354(CASP8)
CSAB103217637(CASP8)
CATY105580035(CASP8)
PANU101009470(CASP8)
TGE112636264(CASP8)
RRO104671864(CASP8)
RBB108532002(CASP8)
TFN117094661(CASP8)
PTEH111547169(CASP8)
CJC100395220(CASP8)
SBQ101053601(CASP8)
CSYR103273365(CASP8)
MMUR105856959(CASP8)
LCAT123643895(CASP8)
OGA100965468(CASP8)
MMU12370(Casp8)
MCAL110291975(Casp8)
MPAH110321675(Casp8)
RNO64044(Casp8)
MCOC116088467(Casp8)
MUN110557662(Casp8)
CGE100689369(Casp8)
MAUA101825474(Casp8)
PLEU114704437(Casp8)
MORG121444834 121458619
AAMP119803862(Casp8)
NGI103738672(Casp8)
HGL101702773(Casp8)
CPOC100713334(Casp8)
CCAN109689613(Casp8)
DORD105981481(Casp8)
DSP122096450(Casp8)
NCAR124980441
OCU100348477(CASP8)
OPI101521762(CASP8)
TUP102498355(CASP8)
CFA488473(CASP8)
CLUD112656364(CASP8)
VVP112922873(CASP8)
VLG121480703(CASP8)
AML100472842(CASP8)
UMR103659742(CASP8)
UAH113250592(CASP8)
UAR123798200(CASP8)
ELK111141026
LLV125094998
MPUF101678102(CASP8)
ORO101365855(CASP8)
EJU114223527(CASP8)
ZCA113919983(CASP8)
MLX118012152(CASP8)
FCA100142684(CASP8)
PYU121030909(CASP8)
PBG122481641(CASP8)
PTG102962460(CASP8)
PPAD109260762(CASP8)
AJU106987995(CASP8)
HHV120220675(CASP8)
BTA507481(CASP8)
BOM102272602(CASP8)
BIU109569521(CASP8)
BBUB102412929(CASP8)
CHX102169919(CASP8)
OAS101107334(CASP8)
ODA120854621(CASP8)
CCAD122426570(CASP8)
SSC595105(CASP8)
CFR102508224(CASP8)
CBAI105082299(CASP8)
CDK105099181(CASP8)
VPC102542071(CASP8)
BACU103004642(CASP8)
LVE103077054(CASP8)
OOR101281780(CASP8)
DLE111171726(CASP8)
PCAD102988082(CASP8)
PSIU116757029(CASP8)
ECB100066502(CASP8)
EPZ103565685(CASP8)
EAI106823493(CASP8)
MYB102246377(CASP8)
MYD102761550(CASP8)
MMYO118661495(CASP8)
MLF102439369(CASP8)
MNA107533931(CASP8)
PKL118709494(CASP8)
HAI109379228(CASP8)
DRO112307787(CASP8)
SHON118985238(CASP8)
AJM119065511(CASP8)
PDIC114494575(CASP8)
PHAS123824482(CASP8)
MMF118625346(CASP8)
RFQ117025976(CASP8)
PALE102878181(CASP8)
PGIG120587528(CASP8)
PVP105298127(CASP8)
RAY107503155(CASP8)
MJV108398898(CASP8)
TOD119256101(CASP8)
SARA101543078(CASP8)
LAV100660542(CASP8) 100663575
TMU101344302
DNM101432853(CASP8)
MDO100017025(CASP18) 100617599(CASP8)
GAS123240075 123242697
SHR100931580(CASP8)
PCW110197193(CASP8)
OAA100082949(CASP8) 100087835
GGA395284(CASP8) 693266(CASP18)
PCOC116233978 116233979
MGP100541513 100541666
CJO107316523 107316524
NMEL110399293 110400694
APLA101803161(CASP8) 106014283
ACYG106040002 106040004
AFUL116490786 116491006
TGU100222284 100223333
LSR110484576(CASP8) 110484625
SCAN103814506 103814507(CASP8)
PMOA120497940 120498528
OTC121335473 121335530
PRUF121356474 121356691
GFR102044546 102044717
FAB101814031 101815602
PHI102110759
CCAE111931990
CCW104693779 120410336
CBRC103612136(CASP8)
ETL114055714 114055715
ZAB102073111(CASP8) 102073459
FPG101916968(CASP8) 106113022
FCH106630990(CASP8)
CLV102084608 102084797
EGZ104130511(CASP8)
NNI104010196(CASP8)
PLET104623365 104625043(CASP8)
PCRI104032112
ACUN113482526 113482527
TALA104356172 104357512(CASP8)
PADL103923440 103924262(CASP8)
ACHC115342550 115343326
HALD104319289 104322668
CCRI104156046(CASP8) 104158038
CSTI104549333 104555644
EHS104504336 104514809(CASP8)
CMAC104478549(CASP8) 104485083
FGA104082182
GSTE104255507(CASP8) 104262083
LDI104342577(CASP8) 104346345
MNB103772020(CASP8)
OHA104334215(CASP8)
AAM106492412 106492473(CASP8)
AROW112976408(CASP8) 112976426
NPD112956289 112956309
DNE112988234(CASP8) 112988375
ASN102384848 102385102
AMJ102573591(CASP8) 102575862(CASP18)
CPOO109323090
GGN109301903
PSS102446244 102447455
CMY102931356 102934251
CPIC101934006 101934828
TST117884831 117885137
CABI116836075(CASP8) 116836078
MRV120374759(CASP8) 120374760
XLA373559(casp8.L)
XTR100495471(casp8)
NPR108795080
RTEM120943730
BBUF121008461
BGAR122945081
DRE100049706(casp8l1) 557302(casp8l2) 561021(casp22) 58022(casp8)
SRX107705601 107747226 107748560 107748577 107756543
SANH107660005 107660083 107660089 107670339 107672910 107680357 107688858 107688860 107689487
SGH107555418 107555445 107560797 107566313 107597346
CCAR109052822 109053966 109053967 109053969 109064153 109083181 109090355
CAUA113048839 113050791 113050793 113088368 113093418 113093474 113108941
PPRM120469557(casp10) 120470089(casp22) 120491686
MAMB125266561(casp22) 125268421 125269841(casp10) 125274320(casp8l1) 125274321
IPU100304635 108266930(casp10) 108273098(casp8) 108273129
PHYP113524385 113525919 113538271
SMEO124382628(casp8) 124382766(casp10)
TFD113634469(casp8) 113654221(casp10)
AMEX103021896 103036076 103036379 103037118
EEE113574024 113582334 113588302
TRU101061322 101075191 101075631
TNGGSTEN00031473G001
LCO104924422 104938225 104938227
NCC104948647 104966261
CGOB115022634 115022799 115026772
ELY117249157(casp10) 117271493(casp8) 117271616
EFO125899933(casp10) 125902003(casp8) 125902004
PLEP121939222 121949527(casp10) 121951363(casp8) 121951365
SLUC116048004(casp10) 116055058 116055079(casp8)
ECRA117953418(casp10) 117954805(casp8) 117954806
PFLV114563975 114565779 114565858
GAT100653426(casp8) 100653427(casp10) 120816322
PPUG119209177(casp8) 119209185 119209565 119209566 119229023(casp10)
MSAM119902446 119902447 119902448 119904125(casp10)
CUD121520232 121520520 121520654 121522126(casp10)
ALAT119010726 119011511 119026092(casp10)
MZE101470036 101475706 101478827 101481407 106674852 106676518 112430088 112430089
ONL100702139 100702676 102079913 109194206
OAU116321529 116321530 116321532 116321534 116321548 116322912(casp10)
OLA100049400(casp8) 100125536
OML112147424(casp8) 112147426
XMA102237443 102237850 111608841
XCO114147136 114147142 114147894 114151637
XHE116721891 116722140 116722737
PRET103459939 103478931 103478932 108167062
PFOR103134398 103151557 103151574
PLAI106958504 106961428
PMEI106924075 106924079 106926427 106934087
GAF122840130(casp10) 122840676 122840680 122840684 122840687 122841345
CVG107082055 107086818 107086824
CTUL119779267 119779311 119780252(casp10)
GMU124869876 124870505(casp8) 124871764(casp10)
NFU107384290 107384292 107389982
KMR108238317(casp8) 108238318 108239714(casp10)
ALIM106512618 106512902 106517939
NWH119414875(casp8) 119414876 119418871(casp10)
AOCE111586360 111588089 111588095 111588107
MCEP125018228(casp10)
CSEM103396237 103396239
POV109631024 109637364 109641073
SSEN122760804(casp10) 122761240(casp8) 122775595
HHIP117755099(casp10) 117778078(casp8) 117778299
HSP118117212 118117657(casp8) 118120504(prkra) 118120505
LCF108881527 108883888
SDU111218362 111229030(casp8)
SLAL111648895 111666542(casp8)
XGL120799083(casp8) 120799085 120801861(casp10)
HCQ109520533
BPEC110166585 110173494(casp8) 110173519
MALB109958094
BSPL114844036(casp8) 114844038 114847689(casp10)
SASA106569473 106582462 106586254
OTW112225661(casp10) 112226687(casp8) 112245958 112247430
OMY101268911(casp8) 110502170 110508466 110520142 110530629
OGO124009734 124041578(casp8) 124043892
ONE115102767 115109425 115114693 115119721
SALP111956905 111957166 111959935 111975582 111979249 111979568
SNH120020199(casp8) 120056102 120058267 120063683
CCLU121536756(casp10) 121554909 121581147
ELS105006190 105009870 105021259 105021271 105024762
SFM108918550 108918555 108920617 108920619(casp8) 108932283
PKI111852220 111852221 111859671 111859672
AANG118214013 118222448
LOC102697443(casp8) 102697635 102697829
PSPA121321941 121322097 121322099 121322100 121322854 121322856 121323064 121323616
ARUT117408587 117414260 117426351 117426603 117426878
LCM102349989 102355925 102356202
CMK103171902
RTP109915462 109929740 109932037
BFO118406076 118419602 118420396 118420457 118428976 118430951
BBEL109470585 109473442 109476237 109476238 109481944
CIN100183123
SCLV120339721
SPU105445989 585496
APLC110982622 110986601
SKO100369664 100375416
DMEDmel_CG7486(Dredd)
DER6555550
DSE6615883
DSIDsimw501_GD16467(Dsim_Dredd)
DYADyak_GE16575(Dyak_Dredd)
DAN6504896
DSR110182574
DPO4816060
DPE6599948
DMN108153528
DWI6644580
DGR6565876
DMODmoj_GI21675
DAZ108619540
DNV108656798
DHE111592986
DVI6633308
CCAT101452999
BOD106618890
MDE101900122
SCAC106085869
LCQ111685143 111685144
LSQ119606412 119614517 119614518
AGAAgaP_AGAP011693(CASPL1)
ACOZ120958709
AARA120903661
ASTE118505920
AAG5563818
AALB115262725
CQUCpipJ_CPIJ014995
CPII120417982
CNS116339550
BCOO119074810
AME724930
ACER107999646
ALAB122718768
BIM100741190
BBIF117214682
BVK117233219
BVAN117166605
BTER100652115
BPYO122568216
CCAL108627268
OBB114878450
NMEA116429669
CGIG122403524
SOC105205440
MPHA105828235
AEC105147270
ACEP105625685
PBAR105429159
VEM105558011
HST105190451
DQU106743797
CFO105248277
FEX115238151
LHU105678455
PGC109856665
OBO105280305
PCF106791240
PFUC122515454
VPS122635758
NVI100680000
CSOL105360146
MDL103579887
CGLO123267651
FAS105274222
DAM107048127
AGIF122861074
CCIN107273653
TCA661095(Dredd)
DPA109534720
SOY115878704
ATD109598530
CSET123312727
AGB108903568
LDC111513505
NVL108556913
APLN108732887
PPYR116164321 116164534
OTU111420306 111421814
BMOR100141428(Dredd)
BMAN114248879
MSEX115442338 115442360 119188347
DPLKGM_212093
BANY112043434
PMAC106720189
PPOT106109353
PXU106127201
PRAP110996855
ZCE119835017
HAW110369675
TNL113491750
OFU114354995
PXY105390324
CLEC106661122
NLU111054479
PHUPhum_PHUM574530
FOC113202554
TPAL117639241 117654141
ZNE110835030
CSEC111866938
DMK116930618
PVM113822604
PJA122245041 122251197 122251198 122266756
PCHN125025732 125041108 125044277 125044384
HAME121855632 121871725
PCLA123765010 123765863 123765865
PTRU123508576 123508705 123518818
HAZT108668981 108675143
EAF111715246
PPOI119093108 119093774
DSV119466258
RSAN119371744
RMP119179927
CSCU111615099
PCAN112560982
BGT106054001 106078261 106078428
GAE121372573 121384420 121387437 121387656 121387773
HRF124110723 124110963 124111376 124111841 124112816 124116383 124125281 124132113 124134993 124143787 124149539 124151584 124152864 124152865
HRJ124257135 124262809 124265296 124267644 124273512 124273718 124275672 124277624 124279661 124279734 124280614 124284330 124288477
CRG105318843 105332613 105340890 105346084 117691806 117691813 117692646
MYI110449259
PMAX117317156 117317363 117327557 117328816 117328818
MMER123527736 123538317 123551007 123553922 123553927 123557524
LAK106152179 106171044
SMMSmp_141270
NVE5505811
EPA110231936
ATEN116289374 116297720 116298542 116298545
ADF107335805
AMIL114961919
PDAM113682606
SPIS111335203
DGT114530339 114534211 114539385
XEN124458193
HMG100203004 100207763 100579132(casp8) 105843821 105846973
AQU100638885 105313668 105315966 105316143 105316853 109581722 109584594
 » show all
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)
DOI:10.1128/mmbr.64.4.821-846.2000
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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