CASP8 MCH5

CASP8 ;
MCH5 ;
Caspase-8 ;
CASP-8 ;
Apoptotic cysteine protease ;
Apoptotic protease Mch-5 ;
CAP4 ;
FADD-homologous ICE/ced-3-like protease ;
FADD-like ICE ;
FLICE ;
ICE-like apoptotic protease 5 ;
MORT1-associated ced-3 homolog ;
MACH

catalytic activity:Strict requirement for Asp at position P1 and has a preferred cleavage sequence of (Leu/Asp/Val) -Glu-Thr-Asp-|- (Gly/Ser/Ala) . ,disease:Defects in CASP8 are the cause of caspase-8 deficiency (CASP8D) [MIM:607271]. CASP8D is a disorder resembling autoimmune lymphoproliferative syndrome (ALPS) . It is characterized by lymphadenopathy , splenomegaly , and defective CD95-induced apoptosis of peripheral blood lymphocytes (PBLs) . It leads to defects in activation of T-lymphocytes , B-lymphocytes , and natural killer cells leading to immunodeficiency characterized by recurrent sinopulmonary and herpes simplex virus infections and poor responses to immunization. ,domain:Isoform 9 contains a N-terminal extension that is required for interaction with the BCAP31 complex. ,function: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. Isoforms 5 , 6 , 7 and 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex. ,online information:CASP8 mutation db ,polymorphism:Genetic vaiations in CASP8 are associated with reduced risk of lung cancer [MIM:211980] in a population of Han Chinese subjects. Genetic vaiations are also associated with decreased risk of cancer of various other forms including esophageal , gastric , colorectal , cervical , and breast , acting in an allele dose-dependent manner. ,PTM:Generation of the subunits requires association with the death-inducing signaling complex (DISC) , whereas additional processing is likely due to the autocatalytic activity of the activated protease. GZMB and CASP10 can be involved in these processing events. ,PTM:Phosphorylated upon DNA damage , probably by ATM or ATR. ,similarity:Belongs to the peptidase C14A family. ,similarity:Contains 2 DED (death effector) domains. ,subunit:Heterotetramer that consists of two anti-parallel arranged heterodimers , each one formed by a 18 kDa (p18) and a 10 kDa (p10) subunit. Interacts with FADD , CFLAR and PEA15. Isoform 9 interacts at the endoplasmic reticulum with a complex containing BCAP31 , BAP29 , BCL2 and/or BCL2L1. Interacts with TNFAIP8L2. ,tissue specificity:Isoforms 1 , 5 and 7 are expressed in a wide variety of tissues. Highest expression in peripheral blood leukocytes , spleen , thymus , and liver. Barely detectable in brain , testis , and skeletal muscle. ,

angiogenesis , blood vessel development , embryonic epithelial tube formation , neural tube formation , vasculature development , morphogenesis of an epithelium , immune system development , leukocyte differentiation , myeloid leukocyte differentiation , protein complex assembly , proteolysis , apoptosis , induction of apoptosis , heart development , cell death , induction of apoptosis by extracellular signals , activation of pro-apoptotic gene products ,macromolecule catabolic process , embryonic development ending in birth or egg hatching , positive regulation of signal transduction , response to organic substance , regulation of protein kinase cascade , positive regulation of cell communication , positive regulation of protein kinase cascade , regulation of cell death , positive regulation of cell death ,programmed cell death , induction of programmed cell death , death , morphogenesis of embryonic epithelium , neural tube development , hemopoiesis , myeloid cell differentiation , protein catabolic process , macrophage differentiation ,response to cytokine stimulus , response to tumor necrosis factor , tube lumen formation , tube morphogenesis , tube development , regulation of apoptosis , chordate embryonic development , positive regulation of apoptosis , regulation of programmed cell death , positive regulation of programmed cell death , regulation of I-kappaB kinase/NF-kappaB cascade , positive regulation of I-kappaB kinase/NF-kappaB cascade , macromolecular complex subunit organization ,cellular protein catabolic process , cellular macromolecule catabolic process , blood vessel morphogenesis , hemopoietic or lymphoid organ development , embryonic morphogenesis , tissue morphogenesis , protein oligomerization , protein heterooligomerization , proteolysis involved in cellular protein catabolic process , epithelium development , epithelial tube morphogenesis , macromolecular complex assembly , protein complex biogenesis ,

Cytoplasm . Nucleus .