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: Protease; EC 188.8.131.52; Mitochondrial; Membrane protein, integral
Cellular Component: endoplasmic reticulum membrane; internal side of plasma membrane; mitochondrion; endoplasmic reticulum; mitochondrial membrane; mitochondrial intermembrane space; cytosol; nucleus
Molecular Function: peptidase activity; protein binding; serine-type peptidase activity; serine-type endopeptidase activity; unfolded protein binding
Biological Process: mitochondrion organization and biogenesis; cleavage of cytoskeletal proteins during apoptosis; positive regulation of apoptosis; forebrain development; neuron development; response to stress; regulation of multicellular organism growth; positive regulation of caspase activity; proteolysis; cell cycle arrest; adult walking behavior
SS: 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.