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Literature summary for 3.4.21.108 extracted from
- The mitochondrial serine protease HtrA2/Omi: an overview (2008), Cell Death Differ., 15, 453-460.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| additional information | HtrA2/Omi protein levels are upregulated several fold when the unfolded protein response is triggered by heat shock. Transient exposure to elevated temperatures augments the protease activity of human HtrA2/Omi | Homo sapiens | |
| siRNA | siRNA-mediated knockdown of HtrA2/Omi combined with the pan-caspase inhibitor zVAD-fmk almost completely protects HeLa cells from undergoing staurosporine-induced cell death, whereas caspase inhibition alone is significantly less effective | Homo sapiens | |
| tunicamycin | - |
Homo sapiens |  |
Application
| Application | Comment | Organism |
|---|---|---|
| medicine | link between HtrA2/Omi and Parkinsons disease or Alzheimers disease | Homo sapiens |
| medicine | role for HtrA2/Omi in apoptosis | Mus musculus |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| A141S | affects the enzymatic activity of the protease, associated with the development of Parkinsons disease | Homo sapiens |
| G399S | affects the enzymatic activity of the protease, associated with the development of Parkinsons disease | Homo sapiens |
| additional information | mutations in the genes encoding HtrA proteins correlate with Parkinsons disease. Lower HtrA2/Omi phosphorylation levels in brains of patients with Parkinsons disease carrying mutations in PINK1 | Homo sapiens |
| additional information | mutations in the genes encoding HtrA proteins correlate with perinatal lethality in mice | Mus musculus |
| S276C | HtrA2/Omi appears to be correctly processed in cells derived from Mnd2 mice (motor neuron degeneration 2), which are homozygous for a naturally occurring Ser276Cys mutation in the HtrA2/Omi protease domain that greatly reduces its catalytic activity. Mnd2 mice display Parkinsonian phenotype, fail to gain weight, and organs such as the heart, thymus and spleen are dramatically smaller when compared to wild-type littermates. Reduced body weight and progressive loss of neurons in the striatum of the basal ganglia are also evident in mice with a targeted deletion of the HtrA2/Omi gene. HtrA2/Omi-/- mice display a lack of coordination, decreased mobility and tremor | Mus musculus |
| S306A | enzymatically inactive, remains uncleaved | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| ucf-101 | - |
Homo sapiens | |
| ucf-101 | - |
Mus musculus | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| mitochondrion | intermembrane space, HtrA2/Omi is required for mitochondrial homeostasis | Mus musculus | 5739 | - |
| mitochondrion | intermembrane space, HtrA2/Omi is required for mitochondrial homeostasis | Homo sapiens | 5739 | - |
| nucleus | - |
Homo sapiens | 5634 | - |
| periplasm | - |
Escherichia coli | - |
- |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Bacillus sp. (in: Bacteria) | - |
- |
- |
| Bos taurus | - |
- |
- |
| Canis lupus familiaris | - |
- |
- |
| Clostridium sp. | - |
- |
- |
| Drosophila melanogaster | - |
- |
- |
| Escherichia coli | - |
- |
- |
| Homo sapiens | - |
- |
- |
| Macaca mulatta | - |
- |
- |
| Mesorhizobium loti | - |
- |
- |
| Mus musculus | - |
- |
- |
| no activity in Caenorhabditis elegans | - |
- |
- |
| no activity in Mycoplasma genitalium | - |
- |
- |
| no activity in Mycoplasma pneumoniae | - |
- |
- |
| Rattus norvegicus | - |
- |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| brain | - |
Homo sapiens | - |
| HeLa cell | - |
Homo sapiens | - |
| neuron | - |
Mus musculus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| HS1-associated protein X-1 + H2O | HtrA2/Omi-mediated degradation of HS1-associated protein X-1 correlates with extensive cell death in response to etoposide, cisplatin and H2O2 | Mus musculus | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| HtrA/DegP | - |
Escherichia coli |
| HtrA2/Omi | - |
Drosophila melanogaster |
| HtrA2/Omi | - |
Mus musculus |
| HtrA2/Omi | - |
Homo sapiens |
| HtrA2/Omi | - |
Rattus norvegicus |
| HtrA2/Omi | - |
Bos taurus |
| HtrA2/Omi | - |
Canis lupus familiaris |
| HtrA2/Omi | - |
Bacillus sp. (in: Bacteria) |
| HtrA2/Omi | - |
Macaca mulatta |
| HtrA2/Omi | - |
Clostridium sp. |
| HtrA2/Omi | - |
Mesorhizobium loti |
| serine protease HtrA2/Omi | - |
Drosophila melanogaster |
| serine protease HtrA2/Omi | - |
Mus musculus |
| serine protease HtrA2/Omi | - |
Homo sapiens |
| serine protease HtrA2/Omi | - |
Rattus norvegicus |
| serine protease HtrA2/Omi | - |
Bos taurus |
| serine protease HtrA2/Omi | - |
Canis lupus familiaris |
| serine protease HtrA2/Omi | - |
Bacillus sp. (in: Bacteria) |
| serine protease HtrA2/Omi | - |
Macaca mulatta |
| serine protease HtrA2/Omi | - |
Clostridium sp. |
| serine protease HtrA2/Omi | - |
Mesorhizobium loti |
Temperature Range [°C]
| Temperature Minimum [°C] | Temperature Maximum [°C] | Comment | Organism |
|---|---|---|---|
| additional information | - |
functions as a chaperonin at normal temperatures, but relies on its proteolytic activity to prevent the accumulation of misfolded proteins in the periplasmic space at higher temperatures | Escherichia coli |
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