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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:
a) autoimmune lymphoproliferative syndrome type 2A
b) familial non-Hodgkin lymphoma
c) gastric cancers
General
caspase; cysteinyl aspartate-specific proteinase; ICE/CED3 family protease
phosphoprotein
Properties
SIZE: entity length = 521 aa
MW = 59 kD
MOTIF: DED 1 {19-97}
DED 2 {114-187}
Ser phosphorylation site {S216}
histidine residue {H358}
cysteine residue {C401}
Database Correlations
OMIM correlations
MORBIDMAP 601762
UniProt Q92851
PFAM correlations
Entrez Gene 843
KEGG correlations
ENZYME 3.4.22.63
References
- UniProt :accession Q92851
- CASP10base; Note: CASP10 mutation db
http://bioinf.uta.fi/CASP10base/
- Autoimmune lymphoproliferative syndrome
Database (ALPSbase); Caspase-10 mutations causing ALPS type II
http://research.nhgri.nih.gov/ALPS/alpsII_mut.shtml
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=CASP10