ASC2: Proteins and Enzymes

ASC2/POP1 is a PAAD domain only protein originally identified in a bioinformatics screen aimed at understanding molecular apoptosis mechanisms (Pawtokski et al, 2001; reviewed in Fabiola et al, 2006, and Mariathasan and Vuvic, 2003.). ASC2/POP1 has high amino acid sequence homology with ASC (64%), hence it was originally termed ASC2. The PAAD (also known as PYRIN) domain is a conserved sequence motif identified in more than 35 human proteins with putative functions in apoptosis and inflammatory signaling pathways. PAAD was named after the protein families from which it was discovered: pyrin, AIM (absent-in-melanoma), ASC [apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD], and death-domain (DD)-like. PAAD is thought to function as a protein-protein interaction domain, possibly coupling different signaling pathways such as apoptosis, inflammation and cancer. For example, PAADs are capable of homotypic interactions with themselves or other members of the PAAD family, suggesting that they participate in complex protein-interaction networks that link various signalling pathways. In humans, the gene encoding ASC2/POP1 is on chromosome 16p12.1, only 14 kbp away from the ASC locus. The close proximity of ASC2/POP1 to ASC as well as the high sequence homology between them suggest that the ASC2/POP1 and ASC genes arose by gene duplication. Studies have shown that ASC2/POP1 associates with ASC via PADD-PADD interactions and modulates ASC-mediated roles in apoptosis and inflammation. ASC2/POP1 may also have a role in modulating other multidomain PAAD-containing proteins. However, the physiological relevance of ASC2/POP1 remains to be fully elucidated. Human ASC2/POP1 is an 89 amino acid protein and migrates at ~10-12 kDa on SDS-PAGE gels (Stehlik et al, 2003).