ID:HTRA2_HUMAN DESCRIPTION: RecName: Full=Serine protease HTRA2, mitochondrial; EC=3.4.21.108; AltName: Full=High temperature requirement protein A2; Short=HtrA2; AltName: Full=Omi stress-regulated endoprotease; AltName: Full=Serine protease 25; AltName: Full=Serine proteinase OMI; Flags: Precursor; 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. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive. 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. SUBUNIT: Homotrimer. Interacts with MXI2. Interacts with THAP5 under apoptotic conditions. The mature protein, but not the precursor, binds to BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Interacts with BIRC6/bruce. INTERACTION: Q96CA5:BIRC7; NbExp=2; IntAct=EBI-517086, EBI-517623; P02666:CSN2 (xeno); NbExp=2; IntAct=EBI-517086, EBI-5260183; Q9P0J0:NDUFA13; NbExp=6; IntAct=EBI-517086, EBI-372742; Q60855:Ripk1 (xeno); NbExp=2; IntAct=EBI-517086, EBI-529119; P98170:XIAP; NbExp=10; IntAct=EBI-517086, EBI-517127; SUBCELLULAR LOCATION: Mitochondrion intermembrane space. Mitochondrion membrane; Single-pass membrane protein (Potential). Note=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. TISSUE SPECIFICITY: Isoform 1 is ubiquitous. Isoform 2 is expressed predominantly in the kidney, colon and thyroid. DOMAIN: The mature N-terminus is involved in the interaction with XIAP. DOMAIN: The PDZ domain mediates interaction with MXI2. PTM: Autoproteolytically activated. 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. SIMILARITY: Belongs to the peptidase S1B family. SIMILARITY: Contains 1 PDZ (DHR) domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O43464
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006508 proteolysis GO:0006672 ceramide metabolic process GO:0006915 apoptotic process GO:0007005 mitochondrion organization GO:0007568 aging GO:0007628 adult walking behavior GO:0008344 adult locomotory behavior GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage GO:0009635 response to herbicide GO:0010822 positive regulation of mitochondrion organization GO:0010942 positive regulation of cell death GO:0016540 protein autoprocessing GO:0019742 pentacyclic triterpenoid metabolic process GO:0030900 forebrain development GO:0034599 cellular response to oxidative stress GO:0034605 cellular response to heat GO:0035458 cellular response to interferon-beta GO:0040014 regulation of multicellular organism growth GO:0043065 positive regulation of apoptotic process GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0044257 cellular protein catabolic process GO:0045786 negative regulation of cell cycle GO:0048666 neuron development GO:0060548 negative regulation of cell death GO:0070207 protein homotrimerization GO:0071300 cellular response to retinoic acid GO:0071363 cellular response to growth factor stimulus GO:0097193 intrinsic apoptotic signaling pathway GO:0097194 execution phase of apoptosis GO:1901215 negative regulation of neuron death GO:1902176 negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway GO:1903146 regulation of mitophagy GO:1903955 positive regulation of protein targeting to mitochondrion GO:1904924 negative regulation of mitophagy in response to mitochondrial depolarization GO:2001241 positive regulation of extrinsic apoptotic signaling pathway in absence of ligand GO:2001269 positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
