FAS-associated death domain protein interleukin-1B-converting enzyme 2
ICE like apoptotic protease 4
ICE-like apoptotic protease 4
Interleukin 1B converting enzyme 2
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. Isoform C is proteolytically inactive.
Detectable in most tissues. Lowest expression is seen in brain, kidney, prostate, testis and colon.
Involvement in 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. 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. 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.
Belongs to the peptidase C14A family. Contains 2 DED (death effector) domains.
Cleavage by granzyme B and autocatalytic activity generate the two active subunits. Phosphorylated upon DNA damage, probably by ATM or ATR.