Application | Comment | Organism |
---|---|---|
medicine | protease activity of HtrA2 is essential for the production of C161. Processing of amyloid precursor protein into C161 by HtrA2 is a natural event occurring under normal physiological conditions. Direct cleavage of mitochondrial beta-amyloid precursor protein by HtrA2 may prevent mitochondrial dysfunction caused by accumulation of amyloid precursor protein. Regulation of HtrA2 protease activity may be a therapeutic target in Alzheimer disease | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
pCMV-HtrA2 plasmid encoding full-length HtrA2 with a C-terminal FLAG epitope tag transiently transfected into HEK-293 cells. Plasmid expressing either wild-type or mutant HtrA2 (pCMV-delta133 or pCMV-delta133 (S306A)) transiently transfected with a plasmid encoding full-length APP with a C-terminal Myc tag (pCMV-APP695M) and overexpression in HEK-293 cells | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
S276C | motor neuron degeneration (mnd2) mice. Level of cleavage product C161 is remarkably decreased in mnd2 mice in which the serine protease activity of HtrA2 is greatly reduced | Mus musculus |
S306A | proteolytic activity is abolished | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
etoposide | ratio of C161M/APP decreases 66% during 0.0040 mM etoposide-induced apoptosis compared with the non-apoptotic condition | Homo sapiens | |
siRNA | suppresses endogenous HtrA2, which results in almost 2030% reduction of C161 production | Homo sapiens | |
staurosporine | after transiently expressing HtrA2 and APP695M in HEK-293 cells for 24 h, the cells are induced by 0.0001 mM staurosporine, resulting in decreased rather than an increased production level of C161M during apoptosis | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytosol | - |
Homo sapiens | 5829 | - |
mitochondrion | amyloid precursor protein is partly colocalized with HtrA2 in the mitochondria | Homo sapiens | 5739 | - |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
36000 | - |
mature HtrA2, subcellular fractionationing | Homo sapiens |
50000 | - |
full-length HtrA2 | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
amyloid precursor protein + H2O | Homo sapiens | - |
? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Mus musculus | - |
- |
- |
Purification (Comment) | Organism |
---|---|
GST fusions purified by selective binding to glutathione-Sepharose 4B beads | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
amyloid precursor protein + H2O | - |
Mus musculus | ? | - |
? | |
amyloid precursor protein + H2O | - |
Homo sapiens | ? | - |
? | |
amyloid precursor protein + H2O | efficient cleavage by HtrA2 in the normal physiological condition. HtrA2-mediated cleavage product is the C161 fragment encompassing amino acids 535695 of amyloid precursor protein 695. Mature HtrA2 and full-length HtrA2 can process amyloid precursor protein into C161 | Homo sapiens | ? | - |
? | |
amyloid precursor protein-like protein 1 + H2O | processed into two major fragments of 65 and 67 kDa | Homo sapiens | ? | - |
? | |
amyloid precursor protein-like protein 2 + H2O | processed into cleaved fragments of 103 and 109 kDa | Homo sapiens | ? | - |
? | |
additional information | beta-synuclein is not cleaved by HtrA2 | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
HtrA2 | - |
Mus musculus |
HtrA2 | - |
Homo sapiens |
HtrA2 serine protease | - |
Mus musculus |
HtrA2 serine protease | - |
Homo sapiens |
Omi | - |
Mus musculus |
Omi | - |
Homo sapiens |