Tchem CASP8 Caspase-8

Protein Summary

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. 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]

Uniprot Accession IDs

• Q14790
• O14676
• Q14791
• Q14792
• Q14793
• Q14794
• Q14795
• Q14796
• Q15780
• Q15806
• Q53TT5
• Q8TDI1
• Q8TDI2
• Q8TDI3
• Q8TDI4
• Q8TDI5
• Q96T22
• Q9C0K4
• Q9UQ81
• CASP-8

Gene Name

• CASP8

Ensembl ID

• ENST00000264274
• ENSP00000264274
• ENSG00000064012
• ENST00000264275
• ENSP00000264275
• ENST00000323492
• ENSP00000325722
• ENST00000358485
• ENSP00000351273
• ENST00000392258
• ENSP00000376087
• ENST00000392263
• ENSP00000376091
• ENST00000432109
• ENSP00000412523

Symbol

• MCH5
• CAP4
• MACH
• MCH5
• FLICE
• ALPS2B
• Casp-8

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
chemical	1
hub protein	1
protein domain	0.97
protein complex	0.94

Protein Classes

PANTHER Classes

Protein / Hydrolase / Protease / Cysteine Protease / Caspase-8

Protein / Enzyme Modulator / Protease Inhibitor / Caspase-8

DTO Classes

Protein / Enzyme / Protease / Cysteine Protease / Caspase-8

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 3925.21   (req: < 5)

Gene RIFs: 607   (req: <= 3)

Antibodies: 1364   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 3925.21   (req: >= 5)

Gene RIFs: 607   (req: > 3)

Antibodies: 1364   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 52

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 198

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0