Version 5.4
Homo sapiens Gene: CASP8
Summary
InnateDB Gene IDBG-78534.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol CASP8
Gene Name caspase 8, apoptosis-related cysteine peptidase
Synonyms ALPS2B; CAP4; Casp-8; FLICE; MACH; MCH5
Species Homo sapiens
Ensembl Gene ENSG00000064012
Encoded Proteins
IDBP-78536
caspase 8, apoptosis-related cysteine peptidase
IDBP-78538
caspase 8, apoptosis-related cysteine peptidase
IDBP-78540
caspase 8, apoptosis-related cysteine peptidase
IDBP-78546
caspase 8, apoptosis-related cysteine peptidase
IDBP-246002
caspase 8, apoptosis-related cysteine peptidase
IDBP-246006
caspase 8, apoptosis-related cysteine peptidase
IDBP-246012
caspase 8, apoptosis-related cysteine peptidase
IDBP-388329
caspase 8, apoptosis-related cysteine peptidase
IDBP-388330
caspase 8, apoptosis-related cysteine peptidase
IDBP-388331
caspase 8, apoptosis-related cysteine peptidase
IDBP-388332
caspase 8, apoptosis-related cysteine peptidase
IDBP-388333
caspase 8, apoptosis-related cysteine peptidase
IDBP-388334
caspase 8, apoptosis-related cysteine peptidase
IDBP-388335
caspase 8, apoptosis-related cysteine peptidase
IDBP-388338
caspase 8, apoptosis-related cysteine peptidase
IDBP-388339
caspase 8, apoptosis-related cysteine peptidase
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
PMID 17213198
CASP8 has an essential role in the regulation of NF-kappaB function in response to TLR4 stimulation, whereby CASP8 recruitment to IKBKB leads to delayed NF-kappaB nuclear translocation and impaired NF-kappaB transcriptional activity.
PMID 20019748
CASP8 is involved in pro-apoptotic signalling through TLR3 and its activation is TICAM1 (TRIF)-dependent.
PMID 21419663
CASP8 restricts the RIG-I-mediated activation of IRF3 by catalytically cleaving RIPK1, and subsequently converting RIPK1 from a signalling enhancer to a signalling inhibitor.
InnateDB Annotation from Orthologs
Summary
PMID 21419663
[Mus musculus] Casp8 restricts the RIG-I-mediated activation of Irf3 by catalytically cleaving Ripk1, and subsequently converting Ripk1 from a signalling enhancer to a signalling inhibitor.
Entrez Gene
Summary This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD. This protein was detected in the insoluble fraction of the affected brain region from Huntington disease patients but not in those from normal controls, which implicated the role in neurodegenerative diseases. Many alternatively spliced transcript variants encoding different isoforms have been described, although not all variants have had their full-length sequences determined. [provided by RefSeq, Jul 2008]
Gene Information
Type Protein coding
Genomic Location Chromosome 2:201233443-201287711
Strand Forward strand
Band q33.1
Transcripts
ENST00000264275 ENSP00000264275
ENST00000323492 ENSP00000325722
ENST00000264274 ENSP00000264274
ENST00000339403
ENST00000358485 ENSP00000351273
ENST00000392266 ENSP00000376094
ENST00000392263 ENSP00000376091
ENST00000392258 ENSP00000376087
ENST00000432109 ENSP00000412523
ENST00000450491 ENSP00000391709
ENST00000440732 ENSP00000396869
ENST00000447616 ENSP00000388306
ENST00000413726 ENSP00000397528
ENST00000437283 ENSP00000407378
ENST00000429881 ENSP00000390641
ENST00000444430 ENSP00000394434
ENST00000424461 ENSP00000390346
ENST00000490682
ENST00000471383
ENST00000490412
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 219 experimentally validated interaction(s) in this database.
They are also associated with 17 interaction(s) predicted by orthology.
Experimentally validated
Total 219 [view]
Protein-Protein 208 [view]
Protein-DNA 6 [view]
Protein-RNA 0
DNA-DNA 5 [view]
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 17 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004175 endopeptidase activity
GO:0004197 cysteine-type endopeptidase activity
GO:0005123 death receptor binding
GO:0005164 tumor necrosis factor receptor binding
GO:0005515 protein binding
GO:0008233 peptidase activity
GO:0008234 cysteine-type peptidase activity
GO:0031625 ubiquitin protein ligase binding
GO:0032403 protein complex binding
GO:0035877 death effector domain binding
GO:0046982 protein heterodimerization activity
GO:0097110 scaffold protein binding
GO:0097153 cysteine-type endopeptidase activity involved in apoptotic process
GO:0097199 cysteine-type endopeptidase activity involved in apoptotic signaling pathway
Biological Process
GO:0001525 angiogenesis
GO:0001841 neural tube formation
GO:0002224 toll-like receptor signaling pathway
GO:0002756 MyD88-independent toll-like receptor signaling pathway
GO:0006508 proteolysis
GO:0006915 apoptotic process
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006921 cellular component disassembly involved in execution phase of apoptosis
GO:0007507 heart development
GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors
GO:0009409 response to cold
GO:0016032 viral process
GO:0030101 natural killer cell activation
GO:0030225 macrophage differentiation
GO:0032025 response to cobalt ion
GO:0032355 response to estradiol
GO:0032496 response to lipopolysaccharide
GO:0034138 toll-like receptor 3 signaling pathway
GO:0034142 toll-like receptor 4 signaling pathway
GO:0034612 response to tumor necrosis factor
GO:0035666 TRIF-dependent toll-like receptor signaling pathway
GO:0035872 nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0036462 TRAIL-activated apoptotic signaling pathway
GO:0042110 T cell activation
GO:0042113 B cell activation
GO:0042981 regulation of apoptotic process
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043124 negative regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045087 innate immune response (InnateDB)
GO:0045471 response to ethanol
GO:0045651 positive regulation of macrophage differentiation
GO:0045862 positive regulation of proteolysis
GO:0046677 response to antibiotic
GO:0051291 protein heterooligomerization
GO:0051603 proteolysis involved in cellular protein catabolic process
GO:0060546 negative regulation of necroptotic process
GO:0060715 syncytiotrophoblast cell differentiation involved in labyrinthine layer development
GO:0070243 regulation of thymocyte apoptotic process
GO:0070423 nucleotide-binding oligomerization domain containing signaling pathway
GO:0071260 cellular response to mechanical stimulus
GO:0071407 cellular response to organic cyclic compound
GO:0097190 apoptotic signaling pathway
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097193 intrinsic apoptotic signaling pathway
GO:0097194 execution phase of apoptosis
GO:0097202 activation of cysteine-type endopeptidase activity
GO:0097284 hepatocyte apoptotic process
GO:1900740 positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
GO:2001233 regulation of apoptotic signaling pathway
GO:2001238 positive regulation of extrinsic apoptotic signaling pathway
GO:2001239 regulation of extrinsic apoptotic signaling pathway in absence of ligand
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005741 mitochondrial outer membrane
GO:0005815 microtubule organizing center
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0030690 Noc1p-Noc2p complex
GO:0031264 death-inducing signaling complex
GO:0031265 CD95 death-inducing signaling complex
GO:0043005 neuron projection
GO:0043234 protein complex
GO:0044297 cell body
GO:0045121 membrane raft
GO:0097342 ripoptosome
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
ENSMUSG00000026029
View Gene Order
ENSBTAG00000015718
Not yet available
Pathways
NETPATH
NetPath_2
AndrogenReceptor pathway
NetPath_9
TNFalpha pathway
NetPath_26
TWEAK pathway
REACTOME
REACT_25039
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 pathway
REACT_25359
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
REACT_150361
TRIF-mediated programmed cell death pathway
REACT_6809
MyD88-independent cascade pathway
REACT_6783
Toll Like Receptor 3 (TLR3) Cascade pathway
REACT_6894
Toll Like Receptor 4 (TLR4) Cascade pathway
REACT_75776
NOD1/2 Signaling Pathway pathway
REACT_832
Dimerization of procaspase-8 pathway
REACT_1503
Caspase-8 activation by cleavage pathway
REACT_701
Activation, myristolyation of BID and translocation to mitochondria pathway
REACT_900
FasL/ CD95L signaling pathway
REACT_402
TRAIL signaling pathway
REACT_13541
Caspase-mediated cleavage of cytoskeletal proteins pathway
REACT_107
Apoptotic cleavage of cellular proteins pathway
REACT_995
Apoptotic execution phase pathway
REACT_1059
Extrinsic Pathway for Apoptosis pathway
REACT_6802
Innate Immune System pathway
REACT_6966
Toll-Like Receptors Cascades pathway
REACT_578
Apoptosis pathway
REACT_75913
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways pathway
REACT_6900
Immune System pathway
REACT_6890
Activated TLR4 signalling pathway
REACT_964
Intrinsic Pathway for Apoptosis pathway
REACT_25281
TRIF-mediated TLR3/TLR4 signaling pathway
REACT_164011
Regulation by c-FLIP pathway
REACT_1619
Death Receptor Signalling pathway
KEGG
hsa04210
Apoptosis pathway
hsa05010
Alzheimer's disease pathway
hsa04620
Toll-like receptor signaling pathway pathway
hsa04115
p53 signaling pathway pathway
hsa05016
Huntington's disease pathway
hsa05200
Pathways in cancer pathway
hsa04622
RIG-I-like receptor signaling pathway pathway
hsa04621
NOD-like receptor signaling pathway pathway
hsa05416
Viral myocarditis pathway
hsa05142
Chagas disease (American trypanosomiasis) pathway
hsa05145
Toxoplasmosis pathway
INOH
INOH website
TNFR1 signaling pathway pathway
INOH website
Fas signaling pathway pathway
PID NCI
ceramide_pathway
Ceramide signaling pathway
caspase_pathway
Caspase Cascade in Apoptosis
ar_pathway
Coregulation of Androgen receptor activity
avb3_integrin_pathway
Integrins in angiogenesis
tnfpathway
TNF receptor signaling pathway
trail_pathway
TRAIL signaling pathway
hivnefpathway
HIV-1 Nef: Negative effector of Fas and TNF-alpha
faspathway
FAS (CD95) signaling pathway
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene Hs.599762 Hs.715120
RefSeq NM_001080124 NM_001080125 NM_001228 NM_033355 NM_033356 NM_033358 XM_005246885 XM_005246886 XM_005246887 XM_005246888 XM_005246889 XM_005246890 XM_005246891 XM_005246892 XM_005246896 XM_006712789 XM_006712790 XM_006712791 XM_006712793
HUGO
OMIM
CCDS CCDS2342 CCDS2343 CCDS2345 CCDS42798 CCDS42799
HPRD 03459
IMGT
EMBL
GenPept
RNA Seq Atlas

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

InnateDB is being developed jointly by the Brinkman Laboratory (Simon Fraser University, British Columbia, Canada), the Hancock Laboratory (University of British Columbia, Vancouver, British Columbia) and the Lynn EMBL Australia Group (South Australian Health & Medical Research Institute and Flinders University, Adelaide, Australia).

Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca