CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012393
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Caspase-8 
Protein Synonyms/Alias
 CASP-8; 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; Caspase-8 subunit p18; Caspase-8 subunit p10 
Gene Name
 CASP8 
Gene Synonyms/Alias
 MCH5 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
122ESNLSFLKELLFRINubiquitination[1]
180RSELRSFKFLLQEEIubiquitination[1]
189LLQEEISKCKLDDDMubiquitination[1]
215RVILGEGKLDILKRVubiquitination[1]
220EGKLDILKRVCAQINubiquitination[1]
228RVCAQINKSLLKIINubiquitination[1]
242NDYEEFSKERSSSLEubiquitination[1]
283SESQTLDKVYQMKSKubiquitination[1]
403TSQFTGLKCPSLAGKubiquitination[1]
410KCPSLAGKPKVFFIQubiquitination[1]
520DDKKNMGKQMPQPTFubiquitination[1]
531QPTFTLRKKLVFPSDubiquitination[1]
532PTFTLRKKLVFPSD*ubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Binding to the adapter molecule FADD recruits it to either receptor. The resulting aggregate called death- inducing signaling complex (DISC) performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases. Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC. Cleaves and activates CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10. May participate in the GZMB apoptotic pathways. Cleaves ADPRT. Hydrolyzes the small-molecule substrate, Ac-Asp-Glu-Val-Asp-|-AMC. Likely target for the cowpox virus CRMA death inhibitory protein. Isoform 5, isoform 6, isoform 7 and isoform 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex. 
Sequence Annotation
 DOMAIN 2 80 DED 1.
 DOMAIN 100 177 DED 2.
 ACT_SITE 317 317
 ACT_SITE 360 360
 MOD_RES 188 188 Phosphoserine (By similarity).
 MOD_RES 334 334 Phosphotyrosine.
 MOD_RES 387 387 Phosphoserine; by CDK1.  
Keyword
 3D-structure; Alternative splicing; Apoptosis; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; Host-virus interaction; Hydrolase; Phosphoprotein; Polymorphism; Protease; Reference proteome; Repeat; Thiol protease; Zymogen. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 479 AA 
Protein Sequence
MEGGRRARVV IESKRNFFLG AFPTPFPAEH VELGRLGDSE TAMVPGKGGA DYILLPFKKM 60
DFSRNLYDIG EQLDSEDLAS LKFLSLDYIP QRKQEPIKDA LMLFQRLQEK RMLEESNLSF 120
LKELLFRINR LDLLITYLNT RKEEMERELQ TPGRAQISAY RVMLYQISEE VSRSELRSFK 180
FLLQEEISKC KLDDDMNLLD IFIEMEKRVI LGEGKLDILK RVCAQINKSL LKIINDYEEF 240
SKERSSSLEG SPDEFSNGEE LCGVMTISDS PREQDSESQT LDKVYQMKSK PRGYCLIINN 300
HNFAKAREKV PKLHSIRDRN GTHLDAGALT TTFEELHFEI KPHDDCTVEQ IYEILKIYQL 360
MDHSNMDCFI CCILSHGDKG IIYGTDGQEA PIYELTSQFT GLKCPSLAGK PKVFFIQACQ 420
GDNYQKGIPV ETDSEEQPYL EMDLSSPQTR YIPDEADFLL GMATVNNCVS YRNPAEGTWY 480
IQSLCQSLRE RCPRGDDILT ILTEVNYEVS NKDDKKNMGK QMPQPTFTLR KKLVFPSD 538 
Gene Ontology
 GO:0031265; C:CD95 death-inducing signaling complex; IEA:Compara.
 GO:0044297; C:cell body; IEA:Compara.
 GO:0005813; C:centrosome; IDA:HPA.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0031264; C:death-inducing signaling complex; IDA:UniProtKB.
 GO:0045121; C:membrane raft; IEA:Compara.
 GO:0005741; C:mitochondrial outer membrane; TAS:Reactome.
 GO:0043005; C:neuron projection; IEA:Compara.
 GO:0030690; C:Noc1p-Noc2p complex; IEA:Compara.
 GO:0005634; C:nucleus; IDA:HPA.
 GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB.
 GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; TAS:Reactome.
 GO:0001525; P:angiogenesis; IEA:Compara.
 GO:0006921; P:cellular component disassembly involved in execution phase of apoptosis; TAS:Reactome.
 GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
 GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:UniProtKB.
 GO:0007507; P:heart development; IEA:Compara.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:Reactome.
 GO:0030225; P:macrophage differentiation; IEA:Compara.
 GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB cascade; IMP:UniProtKB.
 GO:0001841; P:neural tube formation; IEA:Compara.
 GO:0070423; P:nucleotide-binding oligomerization domain containing signaling pathway; TAS:Reactome.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IMP:UniProtKB.
 GO:0045651; P:positive regulation of macrophage differentiation; IMP:UniProtKB.
 GO:1900740; P:positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; TAS:Reactome.
 GO:0045862; P:positive regulation of proteolysis; IDA:BHF-UCL.
 GO:0051291; P:protein heterooligomerization; IEA:Compara.
 GO:0051603; P:proteolysis involved in cellular protein catabolic process; IMP:BHF-UCL.
 GO:0046677; P:response to antibiotic; IEA:Compara.
 GO:0032025; P:response to cobalt ion; IEA:Compara.
 GO:0009409; P:response to cold; IEA:Compara.
 GO:0032355; P:response to estradiol stimulus; IEA:Compara.
 GO:0045471; P:response to ethanol; IEA:Compara.
 GO:0032496; P:response to lipopolysaccharide; IEA:Compara.
 GO:0034612; P:response to tumor necrosis factor; IMP:BHF-UCL.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
Interpro
 IPR011029; DEATH-like_dom.
 IPR001875; DED.
 IPR011600; Pept_C14_cat.
 IPR001309; Pept_C14_ICE_p20.
 IPR016129; Pept_C14_ICE_p20_AS.
 IPR002138; Pept_C14_p10.
 IPR002398; Pept_C14_p45.
 IPR015917; Pept_C14_p45_core. 
Pfam
 PF01335; DED
 PF00656; Peptidase_C14 
SMART
 SM00115; CASc
 SM00031; DED 
PROSITE
 PS01122; CASPASE_CYS
 PS01121; CASPASE_HIS
 PS50207; CASPASE_P10
 PS50208; CASPASE_P20
 PS50168; DED 
PRINTS
 PR00376; IL1BCENZYME.