Literature summary for 3.4.21.108 extracted from

Plun-Favreau, H.; Klupsch, K.; Moisoi, N.; Gandhi, S.; Kjaer, S.; Frith, D.; Harvey, K.; Deas, E.; Harvey, R.J.; McDonald, N.; Wood, N.W.; Martins, L.M.; Downward, J.
The mitochondrial protease HtrA2 is regulated by Parkinsons disease-associated kinase PINK1 (2007), Nat. Cell Biol., 9, 1243-1252.

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Activating Compound

Activating Compound	Comment	Organism	Structure
additional information	phosphorylation of HtrA2 increases its proteolytic activtiy. PINK1 modulates the levels of phosphorylated HtrA2. Activation of MEKK3 induces efficient phosphorylation of both full-length and processed HtrA2 on Ser142. In vitro, p38 is also able to phosphorylate around Ser142	Homo sapiens

Application

Application	Comment	Organism
medicine	HtrA2 is regulated by Parkinson's disease-associated kinase PINK1. HtrA2 interacts with PINK1 and that both are components of the same stress-sensing pathway	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
TAP-tagged HtrA2 stably expressed in HEK-293 cells	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
A141S	mutation in HtrA2 identified in patients with Parkinson's disease	Homo sapiens
G399S	mutation in HtrA2 identified in patients with Parkinson's disease, ability of p38gamma to phosphorylate the peptide is decreased	Homo sapiens
additional information	HtrA2 knockout MEFs, no endogenous PINK1. Show decreased mitochondrial membrane potential	Mus musculus
S142A	considerably less phosphorylated by p38gamma in vitro. Markedly lower protease activity than its acidic counterpart	Homo sapiens
S142D	phospho-mimetic HtrA2-mutant, increases the basal ability of HtrA2 to cleave a fluorogenic substrate peptide by about 2fold	Homo sapiens
S400A	considerably less phosphorylated by p38gamma in vitro. Markedly lower protease activity than its acidic counterpart	Homo sapiens
S400D	phospho-mimetic HtrA2-mutant, increases the basal ability of HtrA2 to cleave a fluorogenic substrate peptide by about 3fold	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
additional information	HtrA2 phosphorylation is decreased in brains of patients with Parkinson's disease carrying mutations in PINK1 (Y431H and C575R)	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
mitochondrion	-	Mus musculus	5739	-
mitochondrion	-	Homo sapiens	5739	-

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-
Mus musculus	-	-	-

Purification (Commentary)

Purification (Comment)	Organism
by gel filtration	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
brain	-	Homo sapiens	-
MEF cell	-	Mus musculus	-
SH-SY5Y cell	-	Homo sapiens	-

Synonyms

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

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Release 2023.1 (January 2023)