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Literature summary extracted from

  • Park, H.J.; Kim, S.S.; Seong, Y.M.; Kim, K.H.; Goo, H.G.; Yoon, E.J.; Min, d.o..S.; Kang, S.; Rhim, H.
    Beta-amyloid precursor protein is a direct cleavage target of HtrA2 serine protease. Implications for the physiological function of HtrA2 in the mitochondria (2006), J. Biol. Chem., 281, 34277-34287.
    View publication on PubMed

Application

EC Number Application Comment Organism
3.4.21.108 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(Commentary)

EC Number Cloned (Comment) Organism
3.4.21.108 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

EC Number Protein Variants Comment Organism
3.4.21.108 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
3.4.21.108 S306A proteolytic activity is abolished Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.4.21.108 etoposide ratio of C161M/APP decreases 66% during 0.0040 mM etoposide-induced apoptosis compared with the non-apoptotic condition Homo sapiens
3.4.21.108 siRNA suppresses endogenous HtrA2, which results in almost 20–30% reduction of C161 production Homo sapiens
3.4.21.108 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

EC Number Localization Comment Organism GeneOntology No. Textmining
3.4.21.108 cytosol
-
 Homo sapiens 5829
-
3.4.21.108 mitochondrion amyloid precursor protein is partly colocalized with HtrA2 in the mitochondria Homo sapiens 5739
-

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
3.4.21.108 36000
-
 mature HtrA2, subcellular fractionationing Homo sapiens
3.4.21.108 50000
-
 full-length HtrA2 Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3.4.21.108 amyloid precursor protein + H2O Homo sapiens
-
 ?
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
3.4.21.108 Homo sapiens
-
-
-
3.4.21.108 Mus musculus
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
3.4.21.108 GST fusions purified by selective binding to glutathione-Sepharose 4B beads Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.4.21.108 amyloid precursor protein + H2O
-
 Homo sapiens ?
-
 ?
3.4.21.108 amyloid precursor protein + H2O efficient cleavage by HtrA2 in the normal physiological condition. HtrA2-mediated cleavage product is the C161 fragment encompassing amino acids 535–695 of amyloid precursor protein 695. Mature HtrA2 and full-length HtrA2 can process amyloid precursor protein into C161 Homo sapiens ?
-
 ?
3.4.21.108 amyloid precursor protein + H2O
-
 Mus musculus ?
-
 ?
3.4.21.108 amyloid precursor protein-like protein 1 + H2O processed into two major fragments of 65 and 67 kDa Homo sapiens ?
-
 ?
3.4.21.108 amyloid precursor protein-like protein 2 + H2O processed into cleaved fragments of 103 and 109 kDa Homo sapiens ?
-
 ?
3.4.21.108 additional information beta-synuclein is not cleaved by HtrA2 Homo sapiens ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
3.4.21.108 HtrA2
-
 Homo sapiens
3.4.21.108 HtrA2
-
 Mus musculus
3.4.21.108 HtrA2 serine protease
-
 Homo sapiens
3.4.21.108 HtrA2 serine protease
-
 Mus musculus
3.4.21.108 Omi
-
 Homo sapiens
3.4.21.108 Omi
-
 Mus musculus