- Catalog number
- PDEH100542-01
- Size / count
- 20 µg
- Dry ice
- No
- Hazardous
- No
- Discontinued
- No
- Background
- Caspase-8 (Cysteine-aspartic acid protease 8/Casp8a, also named MCH5, FLICA and MACH alpha 1) is a 28 kDa member of the peptidase C14A family of enzymes. It is widely expressed and is considered an initiating caspase for the apoptotic cascade. Caspase-8 acts on a wide variety of substrates, including procaspases-3, 4, 6, 7, 9 and 10, c-FLIPL and procaspase-8 itself. Human procaspase-8a is a 54-56 kDa, 479 amino acid (aa) protein. It contains two N-terminal death domains (aa 1-177), followed by a catalytic site that utilizes His317Gly318 plus Cys360. Normally, it is an inactive, cytosolic monomer. But following death-domain (DD) containing receptor oligomerization, Caspase-8 is recruited to the death-inducing signaling complex (DISC) that forms around the death domains of the oligomerized receptor. FADD/CAP-1 is recruited first, followed by procaspase-8/CAP-4 and, possibly, c-FLIPL and procaspase-10. The recruitment, or concentration, of procaspase-8 induces homodimerization. This act alone is sufficient for activation. However, the activity level is modest at best, and appears to be directed towards either itself, or c-FLIPL, which is known to form a functional heterodimer with procaspase-8. When directed towards itself, autocleavage occurs first between Asp374Ser375, generating a 43 kDa (p43) N-terminal (aa 1-374) and an 11 kDa C-terminal (aa 375-479) fragment. The C-terminus is further cleaved between Asp384Leu385 to generate a mature p10 subunit (aa 385-479) . The p43 subunit is next cleaved twice, once between Asp216Ser217, and again between Asp210Ser211 to generate a 26 kDa DD-containing prodomain (aa 1-210) with an additional 18 kDa mature p18 subunit (aa 217-374) . p18 and p10 noncovalently associate to form a 28 kDa heterodimer, which subsequently associates with another p18:p10 heterodimer to form an active, mature Caspase-8 molecule. This leaves the DISC to act on downstream apoptotic procaspases. In the event procaspase-8 comes to the DISC complexed with c-FLIPL, c-FLIPL will be cleaved by procaspase-8, generating a p43 fragment that is analogous to the Caspase-8 p43 subunit. This fragment, however, appears not to be an intermediate in a proteolytic cascade. Rather, it serves as a functional subunit, interacting with TRAF2 and activating NF kappa B. This may account for many of the nonapoptotic activities associated with Caspase-8. Mature Human and Mouse Caspase-8a heterodimers are 73% aa identical.
- Abbreviation
- CASP8
- Synonyms
- ALPS2B; Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 12 protein; Apoptotic cysteine protease; Apoptotic protease Mch-5; Apoptotic protease Mch5; CAP4; CASP-8; CASP8; CASP8; Caspase 8; Caspase 8 apoptosis related cysteine peptidase; Caspase-8 subunit p10; CED 3; FADD Like ICE; FADD-homologous ICE/CED-3-like protease; FADD-like ICE; FLICE; FLJ17672; ICE-like apoptotic protease 5; MACH alpha 1/2/3 protein; MACH; MACH beta 1/2/3/4 protein; MCH5; MGC78473; MORT1 associated ced 3 homolog; MORT1-associated CED-3 homolog; OTTHUMP00000163717; OTTHUMP00000163720; OTTHUMP00000163724; OTTHUMP00000163725; OTTHUMP00000165062; OTTHUMP00000165063; OTTHUMP00000165064; OTTHUMP00000206552; OTTHUMP00000206582
- UniProt
- Q14790
- Accession Number
- Q14790
- Expression System
- E.coli
- Tag
- N-Sumo
- Sequence
- Ser217-Asp374
- Field of Research
- Cancer; Cell Biology; Metabolism
- Endotoxin
- < 10 EU/mg of the protein as determined by the LAL method.
- Purity
- > 90% as determined by reducing SDS-PAGE.
- Bioactivity
- Not validated for activity
- Reconstitution
- It is recommended that sterile water be added to the vial to prepare a stock solution of 0.5 mg/mL. Concentration is measured by UV-Vis.
- Shipping Conditions
- This product is provided as lyophilized powder which is shipped with ice packs.
- Storage Conditions
- Generally, lyophilized proteins are stable for up to 12 months when stored at -20 to -80°C. Reconstituted protein solution can be stored at 4-8°C for 2-7 days. Aliquots of reconstituted samples are stable at < -20°C for 3 months.
- Calculated Molecular Weight
- 30.3 kDa
- Observed Molecular Weight
- 37 kDa
- Formulation
- Lyophilized from a 0.2 μm filtered solution in PBS with 5% Trehalose and 5% Mannitol.
- Species
- Human
