Catalytic activity:Cleavage of non-polar aliphatic amino-acids at the P1 position , with a preference for Val , Ile and Met. At the P2 and P3 positions , Arg is selected most strongly with a secondary preference for other hydrophilic residues. ,Disease:Defects in HTRA2 are the cause of Parkinson disease type 13 (PARK13) [MIM:610297 , 168600]. Parkinson disease (PD) is a complex , multifactorial disorder that typically manifests after the age of 50 years , although early-onset cases (before 50 years) are known. PD generally arises as a sporadic condition but is occasionally inherited as a simple mendelian trait. Although sporadic and familial PD are very similar , inherited forms of the disease usually begin at earlier ages and are associated with atypical clinical features. PD is characterized by bradykinesia , resting tremor , muscular rigidity and postural instability , as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins) , in surviving neurons in various areas of the brain. ,Domain:The mature N-terminus is involved in the interaction with XIAP. ,Domain:The PDZ domain mediates interaction with MXI2. ,Function:Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins , IAPs) , leading to an increase in caspase activity , or by a BIRC inhibition-independent , caspase-independent and serine protease activity-dependent mechanism. Isoform 2 seems to be proteolytically inactive. ,PTM:Autoproteolytically activated. ,similarity:Belongs to the peptidase S1B family. ,similarity:Contains 1 PDZ (DHR) domain. ,subcellular location:Predominantly present in the intermembrane space. Released into the cytosol following apoptotic stimuli , such as UV treatment , and stimulation of mitochondria with caspase-8 truncated BID/tBID. ,subunit:Homotrimer. Interacts with MXI2. The mature protein , but not the precursor , binds to BIRC2 , BIRC3 and XIAP. ,tissue specificity:Isoform 1 is ubiquitous; isoform 2 is expressed predominantly in the kidney , colon and thyroid. ,
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