Serine protease HTRA2, mitochondrial (HTRA2)

Serine protease HTRA2, mitochondrial (HTRA2) is a mitochondrial serine protease that forms a homotrimeric structure with a serine protease domain and a regulatory PDZ domain[1][2][4]. It plays essential roles in apoptosis by promoting caspase-independent cell death, mainly through degradation of inhibitor of apoptosis proteins (IAPs), and in maintenance of mitochondrial protein quality through its chaperone activity[2][3]. Upon apoptotic stimuli, HTRA2 is released into the cytosol, exposing its N-terminal AVPS motif which interacts with IAPs to promote cell death[2][4]. The protein is implicated in neurodegenerative diseases (as PARK13 in Parkinson’s disease) and has also been studied as a drug target in oncology, due to its involvement in apoptosis and cellular stress responses[2][3][4]. Its structural activation and regulation involve intricate allosteric and PDZ-mediated mechanisms required for proper protease activity[1][2][3][4].

Other names

HtrA serine peptidase 2HtrA2OmiPRSS25PARK13High temperature requirement protein A2Omi stress-regulated endoproteaseSerine protease 25Serine proteinase OMIHtrA-like serine proteaseEpididymis secretory sperm binding proteinMGCA8

Induction of apoptosis by cleaving inhibitor of apoptosis proteins (IAPs); Chaperone-protease dual activity for mitochondrial protein surveillance