a serine proteinase that normally resides in mitochondrial membranes. It exists in two populations in mitochondria: as an unprocessed form probably attached to the inner mitochondrial membrane through a N-terminal transmembrane domain, and as a processed form containing a reaper motif at its N-terminus. Following apoptotic stimuli it is autoproteolytically activated and released into the cytosol, where it promotes programmed cell death in caspase-dependent and -independent manners. The amino-terminal reaper motif binds to the IAP (inhibitor of apoptosis) proteins cIAP1, cIAP2, and and XIAP, disrupting IAP-caspase complexes in a manner similar to Smac/DIABLO. Phosphorylation by the protein kinase Akt attenuates its serine protease and pro-apoptotic activities. The PDZ domain mediates interaction with Mxi2, an alternatively spliced form of the p38 stress-activated kinase. In contrast to its pro-apoptotic effects, targeted deletion in mice indicates that it is involved in protection against cell stress in striatial neurons. Defects in HTRA2 are the cause of Parkinson disease 13 (PARK13). Four alternatively spliced human isoforms have been described. Note: This description may include information from UniProtKB.
Protein type: EC 188.8.131.52; Membrane protein, integral; Protease; Mitochondrial
Molecular Function: peptidase activity; protein binding; serine-type endopeptidase activity; serine-type peptidase activity; unfolded protein binding
Biological Process: adult walking behavior; cellular protein catabolic process; ceramide metabolic process; DNA damage response, signal transduction resulting in induction of apoptosis; forebrain development; mitochondrion organization and biogenesis; negative regulation of cell cycle; neuron development; pentacyclic triterpenoid metabolic process; positive regulation of apoptosis; positive regulation of caspase activity; protein autoprocessing; proteolysis; regulation of multicellular organism growth; response to herbicide
LTP: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.