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HTRA2 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; Membrane protein, integral; Mitochondrial; Protease
Chromosomal Location of Human Ortholog: 2p13.1
Cellular Component: chromatin; cytoskeleton; cytosol; endoplasmic reticulum membrane; internal side of plasma membrane; membrane; mitochondrial intermembrane space; mitochondrion; nucleus
Molecular Function: identical protein binding; peptidase activity; protein binding; serine-type endopeptidase activity; serine-type peptidase activity
Biological Process: cellular protein catabolic process; DNA damage response, signal transduction resulting in induction of apoptosis; negative regulation of cell cycle; positive regulation of apoptosis; positive regulation of caspase activity; protein autoprocessing; proteolysis
Disease: 3-methylglutaconic Aciduria, Type Viii; Parkinson Disease 13, Autosomal Dominant, Susceptibility To
Reference #:  O43464 (UniProtKB)
Alt. Names/Synonyms: High temperature requirement protein A2; HtrA serine peptidase 2; HtrA-like serine protease; HTRA2; OMI; Omi stress-regulated endoprotease; PARK13; protease, serine, 25; PRSS25; Serine protease 25; Serine protease HTRA2, mitochondrial; Serine proteinase OMI
Gene Symbols: HTRA2
Molecular weight: 48,841 Da
Basal Isoelectric point: 10.07  Predict pI for various phosphorylation states
CST Pathways:  Apoptosis Regulation  |  Death Receptor Signaling  |  Mitochondrial Control of Apoptosis
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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