ID:CASPA_HUMAN DESCRIPTION: RecName: Full=Caspase-10; Short=CASP-10; EC=3.4.22.63; AltName: Full=Apoptotic protease Mch-4; AltName: Full=FAS-associated death domain protein interleukin-1B-converting enzyme 2; Short=FLICE2; AltName: Full=ICE-like apoptotic protease 4; Contains: RecName: Full=Caspase-10 subunit p23/17; Contains: RecName: Full=Caspase-10 subunit p12; Flags: Precursor; FUNCTION: Involved in the activation cascade of caspases responsible for apoptosis execution. Recruited to both Fas- and TNFR-1 receptors in a FADD dependent manner. May participate in the granzyme B apoptotic pathways. Cleaves and activates caspase- 3, -4, -6, -7, -8, and -9. Hydrolyzes the small- molecule substrates, Tyr-Val-Ala-Asp-|-AMC and Asp-Glu-Val-Asp-|-AMC. FUNCTION: Isoform C is proteolytically inactive. CATALYTIC ACTIVITY: Strict requirement for Asp at position P1 and has a preferred cleavage sequence of Leu-Gln-Thr-Asp-|-Gly. SUBUNIT: Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 23/17 kDa (p23/17) (depending on the splicing events) and a 12 kDa (p12) subunit (By similarity). Self-associates. Interacts with FADD and CASP8. Found in a Fas signaling complex consisting of FAS, FADD, CASP8 and CASP10. INTERACTION: Q14790:CASP8; NbExp=5; IntAct=EBI-495095, EBI-78060; O14730:RIOK3; NbExp=4; IntAct=EBI-495095, EBI-1047061; Q13546:RIPK1; NbExp=2; IntAct=EBI-495095, EBI-358507; TISSUE SPECIFICITY: Detectable in most tissues. Lowest expression is seen in brain, kidney, prostate, testis and colon. PTM: Cleavage by granzyme B and autocatalytic activity generate the two active subunits. PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. DISEASE: Defects in CASP10 are the cause of autoimmune lymphoproliferative syndrome type 2A (ALPS2A) [MIM:603909]. ALPS2 is characterized by abnormal lymphocyte and dendritic cell homeostasis and immune regulatory defects. DISEASE: Defects in CASP10 are a cause of familial non-Hodgkin lymphoma (NHL) [MIM:605027]. NHL is a cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss. DISEASE: Defects in CASP10 are a cause of gastric cancer (GASC) [MIM:613659]. A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. SIMILARITY: Belongs to the peptidase C14A family. SIMILARITY: Contains 2 DED (death effector) domains. WEB RESOURCE: Name=CASP10base; Note=CASP10 mutation db; URL="http://bioinf.uta.fi/CASP10base/"; WEB RESOURCE: Name=Autoimmune Lymphoproliferative Syndrome Database (ALPSbase); Note=Caspase-10 mutations causing ALPS type II; URL="http://research.nhgri.nih.gov/ALPS/alpsII_mut.shtml"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CASP10"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/casp10/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
SCOP Domains: 47986 - DEATH domain 52129 - Caspase-like
ModBase Predicted Comparative 3D Structure on Q92851
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.