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CASP8 & FADD-like apoptosis regulator; cellular FLICE-like inhibitory protein; c-FLIP; caspase-8-related protein; casper; caspase-like apoptosis regulatory protein; CLARP; MACH-related inducer of toxicity; MRIT; caspase homolog; CASH; inhibitor of FLICE; I-FLICE; FADD-like antiapoptotic molecule 1; FLAME-1; usurpin (CFLAR, CASH, CASP8AP1, CLARP, MRIT)

Function: - apoptosis regulator protein - may function as a link between cell survival & cell death pathways in mammalian cells - acts as an inhibitor of TNFRSF6 mediated apoptosis - a proteolytic fragment (p43) is likely retained in the death-inducing signaling complex (DISC) thereby blocking further recruitment & processing of caspase-8 at the complex - full length & shorter isoforms have been shown either to induce apoptosis or to reduce TNFRSF-triggered apoptosis - lacks enzymatic (caspase) activity - proteolytically processed; probably by caspase-8 - processing likely occurs at the DISC & generates subunits p43 & p12 - TNFRSF6 stimulation triggers recruitment to the death-inducing signaling complex (DISC) formed by TNFRSF6, FADD & caspase-8 - a proteolytic fragment (p43) stays associated with the DISC - also interacts with caspase-10, caspase-3, TRAF1, TRAF2 & Bcl-X(L) (in vitro) - interacts with HBV protein X Structure: - the caspase domain lacks the active sites residues involved in catalysis - belongs to the peptidase C14A family - contains 2 DED (death effector) domains Alternative splicing: named isoforms=14 Expression: - widely expressed - higher expression in skeletal muscle, pancreas, heart, kidney, placenta, & peripheral blood leukocytes - detected in diverse cell lines - isoform 8 is predominantly expressed in testis & skeletal muscle - repressed by IL-2 after TCR stimulation, during progression to the S-phase of the cell cycle - overexpressed in some cancers

General

caspase; cysteinyl aspartate-specific proteinase; ICE/CED3 family protease

Properties

SIZE: entity length = 480 aa MW = 55 kD MOTIF: domain {1-435} MOTIF: caspase-8 propeptide interaction {1-305} FADD interaction {1-227} caspase-8 interaction {1-195} DED 1 {1-73} DED 2 {92-170} QACRG MOTIF: cysteine residue TRAF1 and TRAF2 interaction {192-480} MOTIF: caspase-3 interaction {192-435} caspase-8 p18/p10 interaction {217-480} Caspase {263-358} caspase-8 interaction {370-480}

References

  1. UniProt :accession O15519
  2. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/CFLARID40065ch2q33.html

Databases & Figures

OMIM 603599 UniProt O15519 PFAM correlations Entrez Gene 8837 Kegg hsa:8837 TRAIL -> caspase 8 -> bid -> smac/diablo -> IAP ...