CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-001449
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Caspase-8 
Protein Synonyms/Alias
 CASP-8; Caspase-8 subunit p18; Caspase-8 subunit p10 
Gene Name
 Casp8 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
226SESRTSDKVYQMKNKacetylation[1, 2]
Reference
 [1] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
 [2] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
 Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
 Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337] 
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. 
Sequence Annotation
 DOMAIN 3 80 DED 1.
 DOMAIN 101 177 DED 2.
 ACT_SITE 319 319 By similarity.
 ACT_SITE 362 362 By similarity.
 MOD_RES 188 188 Phosphoserine.
 MOD_RES 336 336 Phosphotyrosine (By similarity).
 MOD_RES 389 389 Phosphoserine; by CDK1 (By similarity).  
Keyword
 Apoptosis; Complete proteome; Hydrolase; Phosphoprotein; Protease; Reference proteome; Repeat; Thiol protease; Zymogen. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 480 AA 
Protein Sequence
MDFQSCLYAI AEELGSEDLA ALKFLCLDYI PHKKQETIED AQKLFLRLRE KGMLEEGNLS 60
FLKELLFHIS RWDLLVNFLD CNREEMVREL RDPDNAQISP YRVMLFKLSE EVSELELRSF 120
KFLLNNEIPK CKLEDDLSLL EIFVEMEKRT MLAENNLETL KSICDQVNKS LLGKIEDYER 180
SSTERRMSLE GREELPPSVL DEMSLKMAEL CDSPREQDSE SRTSDKVYQM KNKPRGYCLI 240
INNHDFSKAR EDITQLRKMK DRKGTDCDKE ALSKTFKELH FEIVSYDDCT ANEIHEILEG 300
YQSADHKNKD CFICCILSHG DKGVVYGTDG KEASIYDLTS YFTGSKCPSL SGKPKIFFIQ 360
ACQGSNFQKG VPDEAGFEQQ NHTLEVDSSS HKNYIPDEAD FLLGMATVKN CVSYRDPVNG 420
TWYIQSLCQS LRERCPQGDD ILSILTGVNY DVSNKDDRRN KGKQMPQPTF TLRKKLFFPP 480 
Gene Ontology
 GO:0031265; C:CD95 death-inducing signaling complex; IEA:Compara.
 GO:0044297; C:cell body; IEA:Compara.
 GO:0005813; C:centrosome; IEA:Compara.
 GO:0005829; C:cytosol; IEA:Compara.
 GO:0045121; C:membrane raft; IEA:Compara.
 GO:0005739; C:mitochondrion; IDA:MGI.
 GO:0043005; C:neuron projection; IEA:Compara.
 GO:0030690; C:Noc1p-Noc2p complex; IMP:MGI.
 GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; IDA:MGI.
 GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:MGI.
 GO:0001525; P:angiogenesis; IMP:MGI.
 GO:0071260; P:cellular response to mechanical stimulus; IEA:Compara.
 GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:MGI.
 GO:0007507; P:heart development; IMP:MGI.
 GO:0030225; P:macrophage differentiation; IMP:MGI.
 GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB cascade; IEA:Compara.
 GO:0001841; P:neural tube formation; IMP:MGI.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IEA:Compara.
 GO:0045651; P:positive regulation of macrophage differentiation; IEA:Compara.
 GO:0051291; P:protein heterooligomerization; IEA:Compara.
 GO:0051603; P:proteolysis involved in cellular protein catabolic process; IEA:Compara.
 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; IEA:Compara. 
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.