Caspase-8 (CASP-8) (EC 3.4.22.61) (Apoptotic cysteine protease) (Apoptotic protease Mch-5) (CAP4) (FADD-homologous ICE/ced-3-like protease) (FADD-like ICE) (FLICE) (ICE-like apoptotic protease 5) (MORT1-associated ced-3 homolog) (MACH) [Cleaved into: Caspase-8 subunit p18; Caspase-8 subunit p10]
1_MDFSR 6_ NLYDI 11_ GEQLD 16_ SEDLA 21_ SLKFL 26_ SLDYI 31_ PQRKQ 36_ EPIKD 41_ ALMLF 46_ QRLQE 51_ KRMLE 56_ ESNLS 61_ FLKEL 66_ LFRIN 71_ RLDLL 76_ ITYLN 81_ TRKEE 86_ MEREL 91_ QTPGR 96_ AQISA 101_ YRVML 106_ YQISE 111_ EVSRS 116_ ELRSF 121_ KFLLQ 126_ EEISK 131_ CKLDD 136_ DMNLL 141_ DIFIE 146_ MEKRV 151_ ILGEG 156_ KLDIL 161_ KRVCA 166_ QINKS 171_ LLKII 176_ NDYEE 181_ FSKER 186_ SSSLE 191_ GSPDE 196_ FSNGE 201_ ELCGV 206_ MTISD 211_ SPREQ 216_ DSESQ 221_ TLDKV 226_ YQMKS 231_ KPRGY 236_ CLIIN 241_ NHNFA 246_ KAREK 251_ VPKLH 256_ SIRDR 261_ NGTHL 266_ DAGAL 271_ TTTFE 276_ ELHFE 281_ IKPHD 286_ DCTVE 291_ QIYEI 296_ LKIYQ 301_ LMDHS 306_ NMDCF 311_ ICCIL 316_ SHGDK 321_ GIIYG 326_ TDGQE 331_ APIYE 336_ LTSQF 341_ TGLKC 346_ PSLAG 351_ KPKVF 356_ FIQAC 361_ QGDNY 366_ QKGIP 371_ VETDS 376_ EEQPY 381_ LEMDL 386_ SSPQT 391_ RYIPD 396_ EADFL 401_ LGMAT 406_ VNNCV 411_ SYRNP 416_ AEGTW 421_ YIQSL 426_ CQSLR 431_ ERCPR 436_ GDDIL 441_ TILTE 446_ VNYEV 451_ SNKDD 456_ KKNMG 461_ KQMPQ 466_ PTFTL 471_RKKLV
1: Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood (PubMed:23516580, PubMed:35338844, PubMed:35446120, PubMed:8681376, PubMed:8681377, PubMed:8962078, PubMed:9006941, PubMed:9184224). Initiator protease that induces extrinsic apoptosis by mediating cleavage and activation of effector caspases responsible for FAS/CD95-mediated and TNFRSF1A-induced cell death (PubMed:23516580, PubMed:35338844, PubMed:35446120, PubMed:8681376, PubMed:8681377, PubMed:8962078, PubMed:9006941, PubMed:9184224). Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10 (PubMed:16916640, PubMed:8962078, PubMed:9006941). Binding to the adapter molecule FADD recruits it to either receptor FAS/TNFRSF6 or TNFRSF1A (PubMed:8681376, PubMed:8681377). The resulting aggregate called the death-inducing signaling complex (DISC) performs CASP8 proteolytic activation (PubMed:9184224). The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases (PubMed:9184224). Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC (PubMed:9184224). In addition to extrinsic apoptosis, also acts as a negative regulator of necroptosis: acts by cleaving RIPK1 at 'Asp-324', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed:31827280, PubMed:31827281). Also able to initiate pyroptosis by mediating cleavage and activation of gasdermin-C and -D (GSDMC and GSDMD, respectively): gasdermin cleavage promotes release of the N-terminal moiety that binds to membranes and forms pores, triggering pyroptosis (PubMed:32929201, PubMed:34012073). Initiates pyroptosis following inactivation of MAP3K7/TAK1 (By similarity). Also acts as a regulator of innate immunity by mediating cleavage and inactivation of N4BP1 downstream of TLR3 or TLR4, thereby promoting cytokine production (By similarity). May participate in the Granzyme B (GZMB) cell death pathways (PubMed:8755496). Cleaves PARP1 and PARP2 (PubMed:8681376). Independent of its protease activity, promotes cell migration following phosphorylation at Tyr-380 (PubMed:18216014, PubMed:27109099)
2: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex
3: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex
4: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex (Probable). Acts as an inhibitor of the caspase cascade (PubMed:12010809)
5: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex