CASP10

This gene encodes a protein which is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. Mutations in this gene are associated with apoptosis defects seen in type II autoimmune lymphoproliferative syndrome. Three alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq]

Full Name

caspase 10, apoptosis-related cysteine peptidase

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.
Isoform 7 can enhance NF-kappaB activity but promotes only slight apoptosis.
Isoform C is proteolytically inactive.

Biological Process

Activation of cysteine-type endopeptidase activity involved in apoptotic process Source: GO_Central
Apoptotic process Source: GO_Central
Apoptotic signaling pathway Source: Reactome
Cell surface receptor signaling pathway Source: Reactome
Positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
Regulation of apoptotic process Source: Reactome

Cellular Location

Cytosol; Ripoptosome; CD95 death-inducing signaling complex; Cytoplasm

Involvement in disease

Autoimmune lymphoproliferative syndrome 2A (ALPS2A): A disorder of apoptosis that manifests in early childhood and results in the accumulation of autoreactive lymphocytes. It is characterized by non-malignant lymphadenopathy with hepatosplenomegaly, and autoimmune hemolytic anemia, thrombocytopenia and neutropenia.
Familial non-Hodgkin lymphoma (NHL): 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.
Gastric cancer (GASC): 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.

PTM

Cleavage by granzyme B and autocatalytic activity generate the two active subunits.