HtrA2 Antibody #2176

High temperature requirement protein A2 (HtrA2)/Omi is a serine protease with homology to the E. coli HtrA protein (DegP) and is thought to be involved in apoptosis and stress-induced degradation of misfolded proteins (1). While HtrA2 was orignally identified to be present in either the nucleus (1) or endoplasmic reticulum (2), subsequent studies have shown that it localizes in mitochondria and is released during apoptosis (3-7). HtrA2 is produced as a 50 kDa zymogen that is cleaved to generate a 36 kDa mature protein that exposes an amino terminal motif (AVPS) resembling that of the IAP inhibitor Smac/Diablo (3-7). Like Smac, interaction between HtrA2 and IAP family members, such as XIAP, antagonizes their inhibition of caspase activity and protection from apoptosis (3-7). Interestingly, HtrA2 knock-out mice did not show signs of reduced apoptosis, but rather had a loss of neurons in the striatum and a Parkinson's-like phenotype, suggesting that HtrA2 might have a neuroprotective function (8-10). This activity is associated with the protease activity of HtrA2 (8). Furthermore, research studies have shown that loss of function mutations in the HtrA2 gene are associated with Parkinson's disease (11).