serine protease HTRA2, mitochondrial; high temperature requirement protein A2; HtrA2; Omi stress-regulated endoprotease; serine protease 25; serine proteinase OMI (HTRA2, OMI, PRSS25)

Function: - serine protease - proteolytic activity against a non-specific substrate, beta-casein - promotes or induces cell death either by direct binding to & inhibition of IAP protein/BIRC protein family, leading to an increase in caspase activity, or by a BIRC inhibition- independent, caspase-independent & serine protease activity - cleaves THAP5 & promotes its degradation during apoptosis - isoform 2 seems to be proteolytically inactive - cleavage of non-polar aliphatic amino-acids at the P1 position, with a preference for Val, Ile & Met - at the P2 & P3 positions, Arg is selected most strongly with a secondary preference for other hydrophilic residues - autoproteolytically activated - interacts with MXI2 - interacts with THAP5 under apoptotic conditions - the mature protein, but not the precursor, binds to BIRC2, BIRC3 & XIAP Structure: - homotrimer - the mature N-terminus is involved in the interaction with XIAP - the PDZ domain mediates interaction with MXI2 - belongs to the peptidase S1B family - contains 1 PDZ domain (DHR domain) Compartment: - mitochondrial intermembrane space - mitochondrial membrane - single-pass membrane protein (putative) - predominantly present in mitochondrial intermembrane space - released into the cytosol following apoptotic stimuli, such as UV treatment, & stimulation of mitochondria with caspase-8 truncated BID/tBID Alternative splicing: named isoforms=4 Expression: - isoform 1 is ubiquitous - isoform 2 is expressed predominantly in the kidney, colon & thyroid Pathology: - defects in HTRA2 are the cause of Parkinson's disease type 13

General

mitochondrial membrane protein serine protease

Properties

SIZE: entity length = 458 aa MW = 49 kD COMPARTMENT: mitochondria cytoplasm MOTIF: transmembrane domain {105-125} IAP-binding {134-137} Serine protease {166-342} MOTIF: histidine residue {H198} aspartate residue {D228} serine residue {S306} PDZ domain NAME: PDZ domain SITE: 364-445

Database Correlations

OMIM correlations MORBIDMAP 606441 UniProt O43464 PFAM correlations Entrez Gene 27429 Kegg hsa:27429 ENZYME 3.4.21.108

References

UniProt :accession O43464