CASP8 - Caspase-8 - human protein (Function)
 
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CASP8 »  Caspase-8   [ EC 3.4.22.61 ]  (CASP-8)
 
Protein also known as:  FADD-homologous ICE/ced-3-like protease. Cleaved into:  Caspase-8 subunit p10; Caspase-8 subunit p18.
Gene name:  CASP8
Family name: Peptidase C14A
Entry whose protein(s) existence is based on evidence at protein level
extend overview
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GENE REF ISO

Function

 show evidences
Overview 
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.  
2
  • CuratedUniProtKB
Isoforms  Iso 5 , Iso 6 , Iso 7 and Iso 8   Lack the catalytic site and may interfere with the pro-apoptotic activity of the complex.  
3
  • CuratedUniProtKB
GO molecular function 
Cysteine-type endopeptidase activitydefinition[GO:0004197]  
1
  • IDAUniProtKB
Cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0097153]  
1
  • IMPUniProtKB
Cysteine-type endopeptidase activity involved in apoptotic signaling pathwaydefinition[GO:0097199]  
1
  • IMPUniProtKB
Cysteine-type peptidase activitydefinition[GO:0008234]  
1
  • TASPINC
Death effector domain bindingdefinition[GO:0035877]  
1
  • IPIUniProtKB
Peptidase activitydefinition[GO:0008233]  
1
  • IMPUniProtKB
Protein bindingdefinition[GO:0005515]  
36
  • IPIIntAct
  • IPIUniProtKB
Scaffold protein bindingdefinition[GO:0097110]  
1
  • IPIParkinsonsUK-UCL
Tumor necrosis factor receptor bindingdefinition[GO:0005164] silver  
  • IEAOrtholog Compara
Ubiquitin protein ligase bindingdefinition[GO:0031625]  
1
  • IPIUniProtKB
GO biological process 
Activation of cysteine-type endopeptidase activitydefinition[GO:0097202]  
1
  • IDABHF-UCL
Angiogenesisdefinition[GO:0001525] silver  
  • IEAOrtholog Compara
Apoptotic processdefinition[GO:0006915]  
2
  • IMPUniProtKB
  • IGIMGI
Apoptotic signaling pathwaydefinition[GO:0097190]  
1
  • IMPBHF-UCL
B cell activationdefinition[GO:0042113]  
1
  • TASUniProtKB
Cellular response to mechanical stimulusdefinition[GO:0071260]  
1
  • IEPUniProtKB
Cellular response to organic cyclic compounddefinition[GO:0071407] silver  
  • IEAOrtholog Compara
Execution phase of apoptosisdefinition[GO:0097194]  
1
  • IMPUniProtKB
Extrinsic apoptotic signaling pathwaydefinition[GO:0097191]  
1
  • IDAUniProtKB
Extrinsic apoptotic signaling pathway via death domain receptorsdefinition[GO:0008625] silver  
  • IBARefGenome
Heart developmentdefinition[GO:0007507] silver  
  • IEAOrtholog Compara
Hepatocyte apoptotic processdefinition[GO:0097284] silver  
  • IEAOrtholog Compara
Macrophage differentiationdefinition[GO:0030225]  
1
  • TASUniProtKB
Natural killer cell activationdefinition[GO:0030101]  
1
  • TASUniProtKB
Negative regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043124]  
1
  • IMPUniProtKB
Neural tube formationdefinition[GO:0001841] silver  
  • IEAOrtholog Compara
Positive regulation of extrinsic apoptotic signaling pathwaydefinition[GO:2001238] silver  
  • IEAOrtholog Compara
Positive regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043123]  
2
  • IMPUniProtKB
Positive regulation of macrophage differentiationdefinition[GO:0045651]  
1
  • IMPUniProtKB
Positive regulation of proteolysisdefinition[GO:0045862]  
1
  • IDABHF-UCL
Protein heterooligomerizationdefinition[GO:0051291] silver  
  • IEAOrtholog Compara
Proteolysisdefinition[GO:0006508]  
1
  • IDAUniProtKB
Proteolysis involved in cellular protein catabolic processdefinition[GO:0051603]  
1
  • IMPBHF-UCL
Regulation of thymocyte apoptotic processdefinition[GO:0070243] silver  
  • IEAOrtholog Compara
Response to antibioticdefinition[GO:0046677] silver  
  • IEAOrtholog Compara
Response to cobalt iondefinition[GO:0032025] silver  
  • IEAOrtholog Compara
Response to colddefinition[GO:0009409] silver  
  • IEAOrtholog Compara
Response to estradioldefinition[GO:0032355] silver  
  • IEAOrtholog Compara
Response to ethanoldefinition[GO:0045471] silver  
  • IEAOrtholog Compara
Response to lipopolysaccharidedefinition[GO:0032496] silver  
  • IEAOrtholog Compara
Response to tumor necrosis factordefinition[GO:0034612]  
1
  • IMPBHF-UCL
Syncytiotrophoblast cell differentiation involved in labyrinthine layer developmentdefinition[GO:0060715]  
1
  • TASUniProtKB
T cell activationdefinition[GO:0042110]  
1
  • TASUniProtKB
TRAIL-activated apoptotic signaling pathwaydefinition[GO:0036462]  
1
  • IDAParkinsonsUK-UCL
Viral processdefinition[GO:0016032]  
  • IEAUniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 3.4.22.61: Strict requirement for Asp at position P1 and has a preferred cleavage sequence of (Leu/Asp/Val)-Glu-Thr-Asp-|-(Gly/Ser/Ala).  
1
  • CuratedUniProtKB
It is regulated in the following manner
Probably negatively regulated by RFFL through proteasomal degradation. Inhibited by the effector protein NleF that is produced by pathogenic E.coli; this inhibits apoptosis.  
1
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Alzheimer's disease  hsa05010+841  
Apoptosis  hsa04210+841  
Chagas disease (American trypanosomiasis)  hsa05142+841  
Herpes simplex infection  hsa05168+841  
Huntington's disease  hsa05016+841  
Legionellosis  hsa05134+841  
NOD-like receptor signaling pathway  hsa04621+841  
p53 signaling pathway  hsa04115+841  
Pathways in cancer  hsa05200+841  
RIG-I-like receptor signaling pathway  hsa04622+841  
Toll-like receptor signaling pathway  hsa04620+841  
Toxoplasmosis  hsa05145+841  
Tuberculosis  hsa05152+841  
Viral myocarditis  hsa05416+841  
According to Reactome, this protein belongs to the following pathways:
Activation, myristolyation of BID and translocation to mitochondria  REACT_701  
Apoptotic cleavage of cellular proteins  REACT_107  
Apoptotic execution phase  REACT_995  
Caspase-8 activation  REACT_1503  
Caspase-mediated cleavage of cytoskeletal proteins  REACT_13541  
Dimerization of procaspase-8  REACT_832  
FasL/ CD95L signaling  REACT_900  
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10  REACT_25039  
NOD1/2 Signaling Pathway  REACT_75776  
Regulation by c-FLIP  REACT_164011  
TNF signaling  REACT_1432  
TRAIL signaling  REACT_402  
TRIF-mediated programmed cell death  REACT_150361  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Host-virus interaction  definition   [KW-0945]
Molecular function 
Hydrolase  definition   [KW-0378]
Protease  definition   [KW-0645]
Thiol protease  definition   [KW-0788]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Caspase_8
GenomeRNAi: 841
PRO: PR:Q14790
Chemistry
GuidetoPHARMACOLOGY: 1624