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. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive.
Isoform 1 is ubiquitous. Isoform 2 is expressed predominantly in the kidney, colon and thyroid.
Involvement in disease
Defects in HTRA2 are the cause of Parkinson disease type 13 (PARK13) [MIM:610297]. A complex neurodegenerative disorder 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.
Belongs to the peptidase S1B family. Contains 1 PDZ (DHR) domain.
The mature N-terminus is involved in the interaction with XIAP. The PDZ domain mediates interaction with MXI2.
Mitochondrion intermembrane space. Mitochondrion membrane. 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.