Serine Protease HTRA2, Mitochondrial (HTRA2) Human Recombinant Protein

This gene encodes a serine protease. The protein has been localized in the endoplasmic reticulum and interacts with an alternatively spliced form of mitogen-activated protein kinase 14. The protein has also been localized to the mitochondria with release to the cytosol following apoptotic stimulus. The protein is thought to induce apoptosis by binding the apoptosis inhibitory protein baculoviral IAP repeat-containing 4. Nuclear localization of this protein has also been observed. Alternate splicing of this gene results in two transcript variants encoding different isoforms. Additional transcript variants have been described, but their full-length sequences have not been determined. [provided by RefSeq, Jul 2008]

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.

Protein type: Mitochondrial; EC 3.4.21.108; Membrane protein, integral; Protease

Chromosomal Location of Human Ortholog: 2p12

Cellular Component: endoplasmic reticulum membrane; internal side of plasma membrane; cytoskeleton; membrane; mitochondrion; endoplasmic reticulum; mitochondrial membrane; mitochondrial intermembrane space; chromatin; cytosol; nucleus

Molecular Function: peptidase activity; protein binding; serine-type peptidase activity; serine-type endopeptidase activity; unfolded protein binding

Biological Process: protein autoprocessing; mitochondrion organization and biogenesis; DNA damage response, signal transduction resulting in induction of apoptosis; pentacyclic triterpenoid metabolic process; cellular protein catabolic process; positive regulation of apoptosis; forebrain development; positive regulation of caspase activity; neuron development; regulation of multicellular organism growth; response to herbicide; proteolysis; ceramide metabolic process; adult walking behavior; negative regulation of cell cycle

Disease: Parkinson Disease 13, Autosomal Dominant, Susceptibility To