caspase-10; ICE-like apoptotic protease 4; FLICE2; Mch4 protein (CASP10, MCH4)

Function

• role in activation cascade of caspases responsible for apoptosis execution
• recruited to both Fas- & TNFR-1 receptors in a FADD dependent manner
• may participate in granzyme B apoptotic pathways
• cleaves & activates caspase-3, caspase-4, caspase-6, caspase-7, caspase-8, & caspase-9
• hydrolyzes the small-molecule substrates Tyr-Val-Ala-Asp-|-AMC & Asp-Glu-Val-Asp-|-AMC
• isoform C is proteolytically inactive
• self-associates
• interacts with FADD & CASP8
• found in a Fas signaling complex consisting of FAS, FADD, CASP8 & CASP10
• cleavage by granzyme B & autocatalytic activity generate the two active subunits
• phosphorylated upon DNA damage, probably by ATM or ATR
• strict requirement for Asp at position P1
• preferred cleavage sequence of Leu-Gln-Thr-Asp-|-gly

Structure

• heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 23/17 kD (p23/17) (depending on the splicing events) & a 12 kD (p12) subunit
• belongs to the peptidase C14 family
• contains 2 DED (death effector) domains

Alternative splicing

named isoforms=4

Expression

• detectable in most tissues
• lowest expression in brain, kidney, prostate, testis & colon

Pathology

• defects in CASP10 are the cause of:
  • autoimmune lymphoproliferative syndrome type 2A
  • familial non-Hodgkin lymphoma
  • gastric cancers

More general terms

• caspase
• phosphoprotein

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:843
• OMIM: https://mirror.omim.org/entry/137215
• OMIM: https://mirror.omim.org/entry/601762
• OMIM: https://mirror.omim.org/entry/603909
• OMIM: https://mirror.omim.org/entry/605027
• UniProt: http://www.uniprot.org/uniprot/Q92851.html
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=843
• Kegg: http://www.genome.jp/dbget-bin/www_bget?