CASP8
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].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| caspase 8 | MIM:601763 | Ensembl:ENSG00000064012 | HGNC:HGNC:1509 | PA26092 | 2q33.1 |
GO terms in CASP8
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| MF | IDA | GO:0004197 | cysteine-type endopeptidase activity |
| MF | TAS | GO:0004197 | cysteine-type endopeptidase activity |
| MF | IEA | GO:0005123 | death receptor binding |
| MF | IEA | GO:0005164 | tumor necrosis factor receptor binding |
| MF | IPI | GO:0005515 | protein binding |
| MF | IDA | GO:0008233 | peptidase activity |
| MF | IMP | GO:0008233 | peptidase activity |
| MF | TAS | GO:0008234 | cysteine-type peptidase activity |
| MF | IPI | GO:0031625 | ubiquitin protein ligase binding |
| MF | IBA | GO:0035877 | death effector domain binding |
| MF | IPI | GO:0035877 | death effector domain binding |
| MF | IPI | GO:0042802 | identical protein binding |
| MF | IEA | GO:0044877 | protein-containing complex binding |
| MF | IPI | GO:0097110 | scaffold protein binding |
| MF | IBA | GO:0097153 | cysteine-type endopeptidase activity involved in apoptotic process |
| MF | IMP | GO:0097153 | cysteine-type endopeptidase activity involved in apoptotic process |
| MF | IBA | GO:0097199 | cysteine-type endopeptidase activity involved in apoptotic signaling pathway |
| MF | IMP | GO:0097199 | cysteine-type endopeptidase activity involved in apoptotic signaling pathway |
| MF | IBA | GO:0097200 | cysteine-type endopeptidase activity involved in execution phase of apoptosis |
| BP | IDA | GO:0006508 | proteolysis |
| BP | IBA | GO:0006915 | apoptotic process |
| BP | IGI | GO:0006915 | apoptotic process |
| BP | IMP | GO:0006915 | apoptotic process |
| BP | IBA | GO:0006919 | activation of cysteine-type endopeptidase activity involved in apoptotic process |
| BP | TAS | GO:0006919 | activation of cysteine-type endopeptidase activity involved in apoptotic process |
| BP | TAS | GO:0007166 | cell surface receptor signaling pathway |
| BP | IBA | GO:0008625 | extrinsic apoptotic signaling pathway via death domain receptors |
| BP | IEA | GO:0009409 | response to cold |
| BP | TAS | GO:0010803 | regulation of tumor necrosis factor-mediated signaling pathway |
| BP | TAS | GO:0030101 | natural killer cell activation |
| BP | IBA | GO:0030225 | macrophage differentiation |
| BP | TAS | GO:0030225 | macrophage differentiation |
| BP | IEA | GO:0032025 | response to cobalt ion |
| BP | IEA | GO:0032355 | response to estradiol |
| BP | IEA | GO:0032496 | response to lipopolysaccharide |
| BP | TAS | GO:0034138 | toll-like receptor 3 signaling pathway |
| BP | IMP | GO:0034612 | response to tumor necrosis factor |
| BP | TAS | GO:0035666 | TRIF-dependent toll-like receptor signaling pathway |
| BP | IDA | GO:0036462 | TRAIL-activated apoptotic signaling pathway |
| BP | TAS | GO:0039650 | suppression by virus of host cysteine-type endopeptidase activity involved in apoptotic process |
| BP | TAS | GO:0042110 | T cell activation |
| BP | TAS | GO:0042113 | B cell activation |
| BP | IEP | GO:0043123 | positive regulation of I-kappaB kinase/NF-kappaB signaling |
| BP | IMP | GO:0043123 | positive regulation of I-kappaB kinase/NF-kappaB signaling |
| BP | IMP | GO:0043124 | negative regulation of I-kappaB kinase/NF-kappaB signaling |
| BP | IEA | GO:0045471 | response to ethanol |
| BP | IMP | GO:0045651 | positive regulation of macrophage differentiation |
| BP | IDA | GO:0045862 | positive regulation of proteolysis |
| BP | IMP | GO:0051603 | proteolysis involved in cellular protein catabolic process |
| BP | TAS | GO:0060544 | regulation of necroptotic process |
| BP | TAS | GO:0060715 | syncytiotrophoblast cell differentiation involved in labyrinthine layer development |
| BP | TAS | GO:0070423 | nucleotide-binding oligomerization domain containing signaling pathway |
| BP | IEP | GO:0071260 | cellular response to mechanical stimulus |
| BP | IEA | GO:0071407 | cellular response to organic cyclic compound |
| BP | TAS | GO:0071550 | death-inducing signaling complex assembly |
| BP | IMP | GO:0097190 | apoptotic signaling pathway |
| BP | TAS | GO:0097190 | apoptotic signaling pathway |
| BP | IDA | GO:0097191 | extrinsic apoptotic signaling pathway |
| BP | IBA | GO:0097194 | execution phase of apoptosis |
| BP | IMP | GO:0097194 | execution phase of apoptosis |
| BP | TAS | GO:0097194 | execution phase of apoptosis |
| BP | IDA | GO:0097202 | activation of cysteine-type endopeptidase activity |
| BP | TAS | GO:0097296 | activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway |
| BP | TAS | GO:1900740 | positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway |
| BP | IEA | GO:1901216 | positive regulation of neuron death |
| BP | TAS | GO:1902041 | regulation of extrinsic apoptotic signaling pathway via death domain receptors |
| BP | TAS | GO:1902042 | negative regulation of extrinsic apoptotic signaling pathway via death domain receptors |
| CC | IDA | GO:0005654 | nucleoplasm |
| CC | IBA | GO:0005737 | cytoplasm |
| CC | TAS | GO:0005739 | mitochondrion |
| CC | TAS | GO:0005741 | mitochondrial outer membrane |
| CC | IDA | GO:0005829 | cytosol |
| CC | TAS | GO:0005829 | cytosol |
| CC | TAS | GO:0005856 | cytoskeleton |
| CC | IDA | GO:0031264 | death-inducing signaling complex |
| CC | IDA | GO:0031265 | CD95 death-inducing signaling complex |
| CC | IEA | GO:0043005 | neuron projection |
| CC | IEA | GO:0044297 | cell body |
| CC | IEA | GO:0045121 | membrane raft |
| CC | IDA | GO:0097342 | ripoptosome |
Gene expression in normal tissue: CASP8
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in CASP8
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| biocarta | caspasepathway | caspase cascade in apoptosis |
| biocarta | ceramidepathway | ceramide signaling pathway |
| biocarta | deathpathway | induction of apoptosis through dr3 and dr4/5 death receptors |
| biocarta | faspathway | fas signaling pathway (cd95) |
| biocarta | hivnefpathway | hiv-1 nef: negative effector of fas and tnf |
| biocarta | irespathway | internal ribosome entry pathway |
| biocarta | tnfr1pathway | tnfr1 signaling pathway |
| reactome | R-HSA-109581 | Apoptosis |
| reactome | R-HSA-109606 | Intrinsic Pathway for Apoptosis |
| reactome | R-HSA-111465 | Apoptotic cleavage of cellular proteins |
| reactome | R-HSA-140534 | via Death Receptors in the presence of ligand |
| reactome | R-HSA-162582 | Signal Transduction |
| reactome | R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade |
| reactome | R-HSA-166166 | MyD88-independent TLR4 cascade |
| reactome | R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade |
| reactome | R-HSA-168249 | Innate Immune System |
| reactome | R-HSA-168256 | Immune System |
| reactome | R-HSA-168638 | NOD1/2 Signaling Pathway |
| reactome | R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways |
| reactome | R-HSA-168898 | Toll-Like Receptors Cascades |
| reactome | R-HSA-168928 | DDX58/IFIH1-mediated induction of interferon-alpha/beta |
| reactome | R-HSA-2562578 | TRIF-mediated programmed cell death |
| reactome | R-HSA-264870 | Caspase-mediated cleavage of cytoskeletal proteins |
| reactome | R-HSA-3371378 | Regulation by c-FLIP |
| reactome | R-HSA-5213460 | RIPK1-mediated regulated necrosis |
| reactome | R-HSA-5218859 | Regulated Necrosis |
| reactome | R-HSA-5218900 | CASP8 activity is inhibited |
| reactome | R-HSA-5357769 | Caspase activation via extrinsic apoptotic signalling pathway |
| reactome | R-HSA-5357786 | TNFR1-induced proapoptotic signaling |
| reactome | R-HSA-5357801 | Programmed Cell Death |
| reactome | R-HSA-5357905 | Regulation of TNFR1 signaling |
| reactome | R-HSA-5607764 | CLEC7A (Dectin-1) signaling |
| reactome | R-HSA-5621481 | C-type lectin receptors (CLRs) |
| reactome | R-HSA-5660668 | CLEC7A/inflammasome pathway |
| reactome | R-HSA-5675482 | Regulation of necroptotic cell death |
| reactome | R-HSA-69416 | Dimerization of procaspase-8 |
| reactome | R-HSA-73887 | Death Receptor Signalling |
| reactome | R-HSA-75108 | Activation, myristolyation of BID and translocation to mitochondria |
| reactome | R-HSA-75153 | Apoptotic execution phase |
| reactome | R-HSA-75157 | FasL/ CD95L signaling |
| reactome | R-HSA-75158 | TRAIL signaling |
| reactome | R-HSA-75893 | TNF signaling |
| reactome | R-HSA-9013957 | TLR3-mediated TICAM1-dependent programmed cell death |
| reactome | R-HSA-933543 | NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 |
| reactome | R-HSA-937061 | TRIF(TICAM1)-mediated TLR4 signaling |
| wikipathways | WP1433 | Nucleotide-binding Oligomerization Domain (NOD) pathway |
| wikipathways | WP1449 | Regulation of toll-like receptor signaling pathway |
| wikipathways | WP1530 | miRNA Regulation of DNA Damage Response |
| wikipathways | WP1772 | Apoptosis Modulation and Signaling |
| wikipathways | WP1984 | Integrated Breast Cancer Pathway |
| wikipathways | WP2036 | TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway |
| wikipathways | WP2059 | Alzheimers Disease |
| wikipathways | WP231 | TNF alpha Signaling Pathway |
| wikipathways | WP2324 | AGE-RAGE pathway |
| wikipathways | WP2328 | Allograft Rejection |
| wikipathways | WP2359 | Parkin-Ubiquitin Proteasomal System pathway |
| wikipathways | WP2507 | Nanomaterial induced apoptosis |
| wikipathways | WP2513 | Nanoparticle triggered regulated necrosis |
| wikipathways | WP254 | Apoptosis |
| wikipathways | WP314 | Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation |
| wikipathways | WP3639 | Apoptotic Signaling Pathway |
| wikipathways | WP384 | Apoptosis Modulation by HSP70 |
| wikipathways | WP3865 | RIG-I-like Receptor Signaling |
| wikipathways | WP3982 | miRNA regulation of p53 pathway in prostate cancer |
| wikipathways | WP707 | DNA Damage Response |
| wikipathways | WP75 | Toll-like Receptor Signaling Pathway |
| pid | ar_pathway | Coregulation of Androgen receptor activity |
| pid | avb3_integrin_pathway | Integrins in angiogenesis |
| pid | caspase_pathway | Caspase Cascade in Apoptosis |
| pid | ceramide_pathway | Ceramide signaling pathway |
| pid | faspathway | FAS (CD95) signaling pathway |
| pid | hivnefpathway | HIV-1 Nef: Negative effector of Fas and TNF-alpha |
| pid | tnfpathway | TNF receptor signaling pathway |
| pid | trail_pathway | TRAIL signaling pathway |
| netpath | Pathway_AndrogenReceptor | AndrogenReceptor |
| netpath | Pathway_RAGE | RAGE |
| netpath | Pathway_TNFalpha | TNFalpha |
| netpath | Pathway_TWEAK | TWEAK |
| kegg | hsa04115 | p53 signaling pathway - Homo sapiens (human) |
| kegg | hsa04210 | Apoptosis - Homo sapiens (human) |
| kegg | hsa04215 | Apoptosis - multiple species - Homo sapiens (human) |
| kegg | hsa04217 | Necroptosis - Homo sapiens (human) |
| kegg | hsa04620 | Toll-like receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04621 | NOD-like receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04622 | RIG-I-like receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04625 | C-type lectin receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04657 | IL-17 signaling pathway - Homo sapiens (human) |
| kegg | hsa04668 | TNF signaling pathway - Homo sapiens (human) |
| kegg | hsa04932 | Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human) |
| kegg | hsa05010 | Alzheimer,s disease - Homo sapiens (human) |
| kegg | hsa05016 | Huntington,s disease - Homo sapiens (human) |
| kegg | hsa05134 | Legionellosis - Homo sapiens (human) |
| kegg | hsa05142 | Chagas disease (American trypanosomiasis) - Homo sapiens (human) |
| kegg | hsa05145 | Toxoplasmosis - Homo sapiens (human) |
| kegg | hsa05152 | Tuberculosis - Homo sapiens (human) |
| kegg | hsa05161 | Hepatitis B - Homo sapiens (human) |
| kegg | hsa05165 | Human papillomavirus infection - Homo sapiens (human) |
| kegg | hsa05167 | Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human) |
| kegg | hsa05168 | Herpes simplex infection - Homo sapiens (human) |
| kegg | hsa05200 | Pathways in cancer - Homo sapiens (human) |
| kegg | hsa05203 | Viral carcinogenesis - Homo sapiens (human) |
| kegg | hsa05416 | Viral myocarditis - Homo sapiens (human) |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD361 | 5Z-7-Oxozeaenol | 1 |
| iGMDRD772 | BRD4770 | 5 |
| iGMDRD1008 | SR-II-138A | 2 |
| iGMDRD579 | PF750 | 2 |
| iGMDRD670 | ML 210 | 2 |
| iGMDRD781 | Sirolimus | 3 |
| iGMDRD494 | Neopeltolide | 2 |
| iGMDRD71 | Sparfosic acid | 2 |
| iGMDRD446 | LY 2183240 | 3 |
| iGMDRD152 | 179324-69-7 | 4 |
| iGMDRD193 | Fqi1 | 3 |
| iGMDRD639 | YK 4-279 | 3 |
| iGMDRD679 | Bistramide A | 2 |
| iGMDRD280 | CYTOCHALASIN B | 4 |
| iGMDRD394 | BX-795 | 3 |
| iGMDRD255 | SB225002 | 5 |
| iGMDRD171 | Pemetrexed | 2 |
| iGMDRD309 | 17AAG | 1 |
| iGMDRD441 | TW 37 | 2 |
| iGMDRD887 | Compound 23 citrate | 2 |
| iGMDRD74 | Idarubicin | 3 |
| iGMDRD188 | Piperlongumine | 4 |
| iGMDRD100 | Zebularine | 2 |
| iGMDRD562 | Navitoclax | 8 |
| iGMDRD888 | Compound 44 | 2 |
| iGMDRD577 | BIX01294 | 3 |
| iGMDRD60 | Quinoclamine | 3 |
| iGMDRD64 | Parbendazole | 4 |
| iGMDRD355 | Conatumumab | 1 |
| iGMDRD874 | BRD8958 | 1 |
| iGMDRD330 | BRD4132 | 3 |
| iGMDRD248 | BRD4354 | 1 |
| iGMDRD719 | IOX2 | 1 |
| iGMDRD512 | nutlin 3 | 2 |
| iGMDRD607 | Ubistatin B | 2 |
| iGMDRD232 | FTI-277 | 1 |
| iGMDRD79 | Gemcitabine | 4 |
| iGMDRD85 | Ursolic acid | 2 |
| iGMDRD237 | ABT-751 | 2 |
| iGMDRD123 | Isoevodiamine | 1 |
| iGMDRD211 | (1S,3R)-RSL3 | 2 |
| iGMDRD293 | Bleomycin | 1 |
| iGMDRD271 | Brefeldin A | 1 |
| iGMDRD121 | GMX1778 | 2 |
| iGMDRD251 | ML162 | 2 |
| iGMDRD202 | Curcumin | 3 |
| iGMDRD434 | BMS-536924 | 5 |
| iGMDRD77 | Itraconazole | 2 |
| iGMDRD286 | Nsc 632839 | 3 |
| iGMDRD366 | PI-103 | 2 |
| iGMDRD246 | NPC26 | 2 |
| iGMDRD505 | Pevonedistat | 1 |
| iGMDRD322 | FK 866 | 2 |
| iGMDRD42 | Vorinostat | 3 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in CASP8
CLASSFICATION
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