Any feedback?
Information on EC 3.4.21.108 - HtrA2 peptidase and Organism(s) Homo sapiens and UniProt Accession Q92743
for references in articles please use BRENDA:EC3.4.21.108Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
3.4.21.108 HtrA2 peptidaseSpecify your search results
Word Map
- 3.4.21.108
- xiap
- bcl-2
- parkinson
-
proapoptotic
-
caspases
-
caspase-independent
- aif
-
x-linked
- medicine
-
apoptosis-inducing
-
intermembrane
-
htras
- pink1
-
apoptogenic
-
iap-binding
- apoptosome
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
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
Synonyms
omi/htra2, htra2/omi, serine protease omi/htra2, serine protease htra2/omi, serine protease htra2, high temperature requirement a2, htra2 protease, omi/htra2 protease, omi protease, high temperature requirement protein a2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
high temperature requirement A2
HtrA2
HtrA2 protease
HtrA2/Omi
Omi
Omi/HtrA2
serine protease
serine protease HtrA2
HtrA2
-
-
HtrA2 protease
-
-
-
-
HtrA2/Omi
-
-
Omi/HtrA2
-
-
serine protease
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
cleavage of C-N-linkage
hydrolysis of peptide bond
-
-
CAS REGISTRY NUMBER
COMMENTARY
204655-80-1
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(35S) Met-labeled proteolytically inactive S306 form of full length HtrA2 + H2O
?
-
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-IRRVSYSF(Dnp)KK + H2O
?
-
best substrate
-
?
(7-methoxycoumarin-4-yl)acetyl-VTLCAVPS(Dnp)KK + H2O
?
-
cleavage occurs between cysteine and alanine
-
?
(7-methoxycoumarin-4-yl)AIRRVSYSF-(5-amino-2-nitro)benzamide + H2O
?
-
-
-
?
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-His-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoic acid-Ile-Met-Thr + Abu-Tyr-Met-His-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoic acid-Ile-Met-Thr + Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoic acid-Ile-Met-Thr + Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoic acid-Ile-Met-Thr-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoic acid-Ile-Met-Thr + Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoic acid-Ile-Met-Val-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoic acid-Ile-Met-Val + Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoic acid-Ile-Met-Val-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoic acid-Ile-Met-Val + Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoyl-Ile-Met-Thr-Abu-Tyr-Met-His-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoyl-Ile-Met-Thr + Abu-Tyr-Met-His-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoyl-Ile-Met-Thr-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoyl-Ile-Met-Thr + Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoyl-Ile-Met-Thr-Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoyl-Ile-Met-Thr + Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoyl-Ile-Met-Val-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoyl-Ile-Met-Val + Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoyl-Ile-Met-Val-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoyl-Ile-Met-Val + Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
-
-
-
?
35S-beta-casein + H2O
?
-
C-terminus of presenilin-1 interacts the PDZ domain of with Omi/HtrA2, increasing its activity
-
-
?
A beta 40
?
-
HtrA2/Omi binds preferentially to the short form of A beta peptides, the enzyme does not perform degradation by direct hydrolysis
-
-
?
A beta 42
?
-
HtrA2/Omi binds poorly to A beta 42, the enzyme does not perform degradation by direct hydrolysis
-
-
?
alpha-secretase peptide
?
-
HtrA2/Omi does not perform degradation by direct hydrolysis
-
-
?
amyloid precursor protein-like protein 1 + H2O
?
-
processed into two major fragments of 65 and 67 kDa
-
-
?
amyloid precursor protein-like protein 2 + H2O
?
-
processed into cleaved fragments of 103 and 109 kDa
-
-
?
beta-casein
?
-
protease activity is activated by the binding of the PDZ domain of the mature form of Omi to the C-terminal region of the reduced form of Pag
-
-
?
beta-secretase peptide
?
-
HtrA2/Omi does not perform degradation by direct hydrolysis
-
-
?
c-inhibitor of apoptosis protein1 + H2O
?
-
C-terminus of presenilin-1 interacts with the PDZ domain of Omi/HtrA2, increasing its activity
-
-
?
c-inhibitor of apoptosis protein2 + H2O
?
-
C-terminus of presenilin-1 interacts with the PDZ domain of Omi/HtrA2, increasing its activity
-
-
?
FLIP + H2O
?
-
Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein
-
-
?
gamma-secretase peptide
?
-
HtrA2/Omi binds less strongly to gamma-secretase substrate peptide as compared to alpha-secretase substrate peptide and beta-secretase substrate peptide, the enzyme does not perform degradation by direct hydrolysis
-
-
?
parkin + H2O
?
-
using cleavage and binding assays, it is demonstrated that HtrA2 specifically binds to and directly cleaves the E3 ubiquitin ligase Parkin
-
-
?
ped/pea-15
?
-
HtrA2 is a specific interactor of the ped/pea-15 death effector domain and leads to its degradation
-
-
?
reduced bovine serum albumin
?
-
HtrA2-Opt peptides stimulate the delta N-HtrA1 protease activity more than 3fold
-
-
?
thanatos-associated protein 5 (THAP5) + H2O
?
-
in a yeast two-hybrid assay it is shown that Omi/HtrA2 protease interacts with thanatos-associated protein 5. Degradation assays show that thanatos-associated protein 5 is cleaved by Omi/HtrA2
-
-
?
unidentified substrate + H2O
?
-
its cleavage by Omi/HtrA2 leads to permeabilization of the mitochondria outer membrane and release of chytochrome c followed by enhanced caspase activation
-
-
?
WARTS kinase + H2O
?
-
WARTS, WTS, large tumor-suppressor 1 mitotic kinase
-
-
?
Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide) + H2O
?
-
-
-
?
Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide) + H2O
?
-
-
-
?
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
-
-
?
Apollon + H2O
?
-
HtrA2 cleaves Apollon, a huge inhibitor of apoptosis protein, with its serine protease activity, conversely, Apollon ubiquitylates and facilitates proteasomal degradation of HtrA2, thus both downregulate each other
-
-
?
beta-casein + H2O
?
-
main selectivity at position P1 is for non-polar aliphatic amino acids, in particular valine, isoleucine and methionine. At the P2 and P3 positions arginine is selected most strongly with a secondary selection for other hydrophilic residues
-
?
Wilms' tumor suppressor 1 + H2O
?
-
bona fide substrate for HtrA2-mediated proteolysis, cleavage sites are in the C terminus at Val286 and Leu320, resulting in fragments of 20000 and 35000 Da, respectively, while another cleavage site is in the N terminus at Leu91 adjacent to suppression domain
-
-
?
Wilms' tumor suppressor 1 + H2O
?
-
HtrA2 cleaves at, at least, two specific sites. Wilms' tumor suppressor 1 degradation by HtrA2 reveals two major proteolytic products of 20000 Da and 15000 Da, but the same samples immunoblotted with N-Ter antibody reveals major fragment sizes of 35000 Da and 30000 Da. The potential cleavage site that produces the 20000 Da fragment is at Val286, and the potential cleavage site producing the 15000 Da fragment is at Leu320
-
-
?
Wilms' tumor suppressor protein WT1 + H2O
?
-
using a yeat two-hybrid assay WT1 is identified as a binding partner of HtrA2/Omi. HtrA2/Omi cleaves WT1 at multiple binding sites following the treatment of cells with cytotoxic drugs
-
-
?
X-linked inhibitor of apoptosis protein + H2O
?
-
-
-
-
?
X-linked inhibitor of apoptosis protein + H2O
?
-
autocatalytically processing of HtrA2 to the 36-kDa protein fragment, which is required for the cytochrome c-dependent caspase activation, promoting apoptotic cell death
-
-
?
X-linked inhibitor of apoptosis protein + H2O
?
-
C-terminus of presenilin-1 interacts with the PDZ domain of Omi/HtrA2, increasing its activity
-
-
?
X-linked inhibitor of apoptosis protein + H2O
?
-
homotrimeric structure of enzyme is required for executing its activity
-
-
?
X-linked inhibitor of apoptosis protein + H2O
?
-
Omi/HtrA2 cleaves as well as directly binds and inactivates X-linked inhibitor of apoptosis protein to promote caspase activation
-
-
?
additional information
?
-
-
Omi can degrade inhibitor of apoptosis proteins
-
?
additional information
?
-
-
can promote caspase activation and cell death apoptosis
-
?
additional information
?
-
-
induces atypical cell death. Inhibits the caspase-inhibitory activity of XIAP by direct binding to it. Only mature form but not its precursor binds to IAPs
-
?
additional information
?
-
-
role in apoptosis, amino-terminal IAP interaction motif displaces IAPs from caspases, leading to enhanced caspase activity
-
?
additional information
?
-
-
role in apoptosis, binds to XIAP-binding protein
-
?
additional information
?
-
role in apoptosis, degradation of aberrantly folded proteins during conditions of cellular stress
-
?
additional information
?
-
-
role in apoptosis, degradation of aberrantly folded proteins during conditions of cellular stress
-
?
additional information
?
-
-
role in apoptosis, enzyme can induce apoptosis in a caspase-independent manner through its protease activity and in a caspase-dependent manner via its ability to disrupt caspase-IAP interaction
-
?
additional information
?
-
-
does not bind the reversed control peptide A beta 41-1 and peptide H2-Opt
-
-
?
additional information
?
-
-
degradation of inhibitor of apoptosis proteins, IAPs
-
-
?
additional information
?
-
-
HtrA2 cleaves p73alpha in the C-terminal portion
-
-
?
additional information
?
-
-
co-immunoprecipitation show direct interaction of Omi/HtrA2 with optic atrophy protein 1 (OPA1)
-
-
?
additional information
?
-
-
HtrA2 fails to cleave the Wilms' tumor suppressor 1 cofactors Par-4 and BASP1
-
-
?
additional information
?
-
allostery does regulate HtrA2 activity using a non-canonical selective binding pocket in HtrA2 which initiates signal propagation to the distal active site through a complex allosteric mechanism
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
parkin + H2O
?
-
using cleavage and binding assays, it is demonstrated that HtrA2 specifically binds to and directly cleaves the E3 ubiquitin ligase Parkin
-
-
?
thanatos-associated protein 5 (THAP5) + H2O
?
-
in a yeast two-hybrid assay it is shown that Omi/HtrA2 protease interacts with thanatos-associated protein 5. Degradation assays show that thanatos-associated protein 5 is cleaved by Omi/HtrA2
-
-
?
Wilms' tumor suppressor 1 + H2O
?
-
bona fide substrate for HtrA2-mediated proteolysis, cleavage sites are in the C terminus at Val286 and Leu320, resulting in fragments of 20000 and 35000 Da, respectively, while another cleavage site is in the N terminus at Leu91 adjacent to suppression domain
-
-
?
Wilms' tumor suppressor 1 + H2O
?
-
HtrA2 cleaves at, at least, two specific sites. Wilms' tumor suppressor 1 degradation by HtrA2 reveals two major proteolytic products of 20000 Da and 15000 Da, but the same samples immunoblotted with N-Ter antibody reveals major fragment sizes of 35000 Da and 30000 Da. The potential cleavage site that produces the 20000 Da fragment is at Val286, and the potential cleavage site producing the 15000 Da fragment is at Leu320
-
-
?
Wilms' tumor suppressor protein WT1 + H2O
?
-
using a yeat two-hybrid assay WT1 is identified as a binding partner of HtrA2/Omi. HtrA2/Omi cleaves WT1 at multiple binding sites following the treatment of cells with cytotoxic drugs
-
-
?
additional information
?
-
-
can promote caspase activation and cell death apoptosis
-
?
additional information
?
-
-
induces atypical cell death. Inhibits the caspase-inhibitory activity of XIAP by direct binding to it. Only mature form but not its precursor binds to IAPs
-
?
additional information
?
-
-
role in apoptosis, amino-terminal IAP interaction motif displaces IAPs from caspases, leading to enhanced caspase activity
-
?
additional information
?
-
-
role in apoptosis, binds to XIAP-binding protein
-
?
additional information
?
-
role in apoptosis, degradation of aberrantly folded proteins during conditions of cellular stress
-
?
additional information
?
-
-
role in apoptosis, degradation of aberrantly folded proteins during conditions of cellular stress
-
?
additional information
?
-
-
role in apoptosis, enzyme can induce apoptosis in a caspase-independent manner through its protease activity and in a caspase-dependent manner via its ability to disrupt caspase-IAP interaction
-
?
additional information
?
-
-
degradation of inhibitor of apoptosis proteins, IAPs
-
-
?
additional information
?
-
-
HtrA2 cleaves p73alpha in the C-terminal portion
-
-
?
additional information
?
-
-
co-immunoprecipitation show direct interaction of Omi/HtrA2 with optic atrophy protein 1 (OPA1)
-
-
?
additional information
?
-
-
HtrA2 fails to cleave the Wilms' tumor suppressor 1 cofactors Par-4 and BASP1
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
antisense HtrA2
-
significantly inhibits IFN/all-trans retinoic acid-induced degradation of X-linked inhibitor of apoptosis protein
-
DPMFKL
peptide DPMFKL which inhibits protease HtrA1, EC 3.4.21.107, is not inhibitory to enzyme HtrA2 up to 0.1 mM. For protease HtrA2 mutant lacking the regulatory domain, the peptide acts as a competitive inhibitor, displaying a IC50 value of 0.33 mM
etoposide
-
ratio of C161M/APP decreases 66% during 0.0040 mM etoposide-induced apoptosis compared with the non-apoptotic condition
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
vIRF1
-
human herpes virus-8 (HHV-8)-coded oncoprotein, disrupts interactions of GRIM-19 with HtrA2
-
5-[5-(2-nitrophenyl)furfuryliodine]1,3-diphenyl-2-thiobarbituric acid
-
UCF-101
5-[5-(2-nitrophenyl)furfuryliodine]1,3-diphenyl-2-thiobarbituric acid
UCF-101
siRNA
-
suppresses endogenous HtrA2, which results in almost 2030% reduction of C161 production
-
ucf-101
-
0.02 mM abrogates the death effect of the TNF-alpha + zVAD combination
ucf-101
-
blocks protease activity of Omi, protects renal cells from cisplatin-induced cell death, together with 0.05 mM cisplatin, 0.07 mM ucf-101 can block X-linked inhibitor of apoptosis protein degradation
ucf-101
-
treatment of lung epithelial adenocarcinoma cell A549 decreases the cleavage of annexin A2 under both serum withdrawal and cisplatin treatment
additional information
-
Akt abrogates HtrA2/Omi pro-apoptotic function through phosphorylation of serine 212 in cytoplasm and inhibition of its release from the mitochondria in response to cisplatin treatment. Caspase inhibitor z-VAD-FMK reduces the mature HtrA2/Omi-induced cell death by ca. 45%
-
additional information
-
HtrA2 phosphorylation is decreased in brains of patients with Parkinson's disease carrying mutations in PINK1 (Y431H and C575R)
-
additional information
halogen substitutions at peptide inhibitor's Trp1 residue are most effective in improving peptide selectivity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
GRIM-19
-
direct enhancement of HtrA2 activity in vitro. HtrA2-driven destruction of the antiapoptotic X-linked inhibitor of apoptosis protein is augmented
-
heat shock
-
pre-incubation of Omi at 42°C for 30 min results in increased proteolytic activity
-
IFN/all-trans retinoic acid
-
enhances interaction of GRIM-19 with HtrA2. Causes a concurrent release of HtrA2 and GRIM-19 from mitochondria
-
inhibitor of apoptosis protein
in presence of inhibitor of apoptosis protein, catalytic efficiency increases up to 3fold. In presence of its BIR2 and/or BIR3 domains, catalytic efficiency increases up to 2fold. Interaction allosterically modulates HtrA2 activity, the activation occurs through a series of coordinated structural reorganizations at distal regulatory loops, leading to a population shift towards the relaxed conformer
-
L-phenylalanine
-
essential for the formation of a homotrimer and for the HtrA2 serine protease activity
PDZ domain G230A
mutation in recognition sequence of the PDZ domain, shows a significant decrease in the catalytic efficiency
-
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
-
X-linked inhibitor of apoptosis protein
-
i.e. XIAP, binding of XIAP to the Reaper motif of the enzyme results in a marked increase in proteolytic activity
-
staurosporine
-
apoptotic stimulus to release 36-kDa protein fragment of HtrA2 and cytochrome c from the mitochondria to the cytosol
additional information
-
UV irradiation leads to an almost complete disappearance of mitochondrial Omi/HtrA2 and a parallel appearance of Omi/HtrA2 in the cytoplasm, induction of Omi/HtrA2 binding to ped/pea-15
-
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
-
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
-
additional information
-
serine/threonine kinases Akt1 and Akt2 phosphorylate mitochondria-released HtrA2/Omi on serine 212 in vivo and in vitro, which results in attenuation of its serine protease activity and pro-apoptotic function. Akt phosphorylation of HtrA2/Omi at serine 212 is a critical event for attenuation of HtrA2/Omi cleaving X-linked inhibitor of apoptosis protein, although it does not affect HtrA2/Omi-X-linked inhibitor of apoptosis protein complex formation
-
additional information
-
HtrA2 protein level is gradually and significantly increased by up to 10fold in the mitochondria under tunicamycin-induced ER stress
-
additional information
HtrA2/Omi levels rise dramatically within mitochondria at late times during infection with cytomegalovirus
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00158
(7-methoxycoumarin-4-yl)AIRRVSYSF-(5-amino-2-nitro)benzamide
pH 8.0, 45°C
0.0391
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-His-Tyr(3-NO2)-NH2
pH 8.0, 37°C
0.0227
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, 37°C
0.107
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2
pH 8.0, 37°C
0.354
2-aminobenzoic acid-Ile-Met-Thr-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, 37°C
0.0315
2-aminobenzoic acid-Ile-Met-Val-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, 37°C
0.177
2-aminobenzoic acid-Ile-Met-Val-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, 37°C
0.0391
2-aminobenzoyl-Ile-Met-Thr-Abu-Tyr-Met-His-Tyr(3-NO2)-NH2
pH 8.0, temperature not specified in the publication
0.0227
2-aminobenzoyl-Ile-Met-Thr-Abu-Tyr-Met-Phe-Tyr(3-NO2)
pH 8.0, temperature not specified in the publication
0.1072
2-aminobenzoyl-Ile-Met-Thr-Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2
pH 8.0, temperature not specified in the publication
0.0315
2-aminobenzoyl-Ile-Met-Val-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, temperature not specified in the publication
0.1773
2-aminobenzoyl-Ile-Met-Val-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, temperature not specified in the publication
0.00074 - 0.00096
Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide)
0.00074
Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide)
short natural isoform lacking the N-terminal domain, pH 7.5, temperature not specified in the publication
0.00088
Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide)
protease domain, pH 7.5, temperature not specified in the publication
0.00096
Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide)
variant lacking the N-terminal domain, pH 7.5, temperature not specified in the publication
0.0014
beta-casein
PDZ domain deletion mutant, K0.5 value, Hill constant 1.7, 37°C, pH 7.8
-
0.0017
beta-casein
PDZ domain deletion mutant, K0.5 value, Hill constant 1.4, presence of inhibitor of apoptosis domain BIR2, 37°C, pH 7.8
-
0.0017
beta-casein
PDZ domain deletion mutant, K0.5 value, Hill constant 1.5, presence of inhibitor of apoptosis domain BIR3, 37°C, pH 7.8
-
0.0018
beta-casein
PDZ domain deletion mutant, K0.5 value, Hill constant 1.5, presence of inhibitor of apoptosis protein, 37°C, pH 7.8
-
0.0023
beta-casein
wild-type, K0.5 value, Hill constant 1.6, presence of inhibitor of apoptosis domain BIR2, 37°C, pH 7.8
-
0.0023
beta-casein
wild-type, K0.5 value, Hill constant 1.8, presence of inhibitor of apoptosis domain BIR3, 37°C, pH 7.8
-
0.0023
beta-casein
wild-type, K0.5 value, Hill constant 2.8, 37°C, pH 7.8
-
0.0027
beta-casein
wild-type, K0.5 value, Hill constant 1.5, presence of inhibitor of apoptosis protein, 37°C, pH 7.8
-
0.003
beta-casein
mutant G230A, K0.5 value, presence of inhibitor of apoptosis protein, 37°C, pH 7.8
-
0.00302
beta-casein
mutant comprising N-terminal and serine protease domains, pH 8.0, 37°C
-
0.0032
beta-casein
mutant G230A, K0.5 value, presence of inhibitor of apoptosis domain BIR2, 37°C, pH 7.8
-
0.0035
beta-casein
mutant G230A, K0.5 value, presence of inhibitor of apoptosis domain BIR3, 37°C, pH 7.8
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.05
(7-methoxycoumarin-4-yl)AIRRVSYSF-(5-amino-2-nitro)benzamide
pH 8.0, 45°C
0.22
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-His-Tyr(3-NO2)-NH2
pH 8.0, 37°C
0.33
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, 37°C
0.17
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2
pH 8.0, 37°C
0.01
2-aminobenzoic acid-Ile-Met-Thr-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, 37°C
0.13
2-aminobenzoic acid-Ile-Met-Val-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, 37°C
0.08
2-aminobenzoic acid-Ile-Met-Val-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, 37°C
0.22
2-aminobenzoyl-Ile-Met-Thr-Abu-Tyr-Met-His-Tyr(3-NO2)-NH2
pH 8.0, temperature not specified in the publication
0.33
2-aminobenzoyl-Ile-Met-Thr-Abu-Tyr-Met-Phe-Tyr(3-NO2)
pH 8.0, temperature not specified in the publication
0.17
2-aminobenzoyl-Ile-Met-Thr-Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2
pH 8.0, temperature not specified in the publication
31.5
2-aminobenzoyl-Ile-Met-Val-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, temperature not specified in the publication
0.08
2-aminobenzoyl-Ile-Met-Val-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, temperature not specified in the publication
0.029
Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide)
protease domain, pH 7.5, temperature not specified in the publication
0.029
Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide)
variant lacking the N-terminal domain, pH 7.5, temperature not specified in the publication
0.03
Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide)
short natural isoform lacking the N-terminal domain, pH 7.5, temperature not specified in the publication
0.0039
beta-casein
mutant comprising N-terminal and serine protease domains, pH 8.0, 37°C
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
31.13
(7-methoxycoumarin-4-yl)AIRRVSYSF-(5-amino-2-nitro)benzamide
pH 8.0, 45°C
5.623
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-His-Tyr(3-NO2)-NH2
pH 8.0, 37°C
14.53
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, 37°C
1.588
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2
pH 8.0, 37°C
0.028
2-aminobenzoic acid-Ile-Met-Thr-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, 37°C
4.17
2-aminobenzoic acid-Ile-Met-Val-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, 37°C
0.681
2-aminobenzoic acid-Ile-Met-Val-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, 37°C
5.62
2-aminobenzoyl-Ile-Met-Thr-Abu-Tyr-Met-His-Tyr(3-NO2)-NH2
pH 8.0, temperature not specified in the publication
14.53
2-aminobenzoyl-Ile-Met-Thr-Abu-Tyr-Met-Phe-Tyr(3-NO2)
pH 8.0, temperature not specified in the publication
1.58
2-aminobenzoyl-Ile-Met-Thr-Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2
pH 8.0, temperature not specified in the publication
4.117
2-aminobenzoyl-Ile-Met-Val-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, temperature not specified in the publication
0.68
2-aminobenzoyl-Ile-Met-Val-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
pH 8.0, temperature not specified in the publication
30.27
Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide)
variant lacking the N-terminal domain, pH 7.5, temperature not specified in the publication
33.03
Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide)
protease domain, pH 7.5, temperature not specified in the publication
40.5
Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide)
short natural isoform lacking the N-terminal domain, pH 7.5, temperature not specified in the publication
0.26
beta-casein
mutant G230A, presence of inhibitor of apoptosis domain BIR3, 37°C, pH 7.8
-
0.29
beta-casein
PDZ domain deletion mutant, Hill constant 1.7, 37°C, pH 7.8
-
0.44
beta-casein
mutant G230A, presence of inhibitor of apoptosis domain BIR2, 37°C, pH 7.8
-
0.51
beta-casein
mutant G230A, presence of inhibitor of apoptosis protein, 37°C, pH 7.8
-
0.51
beta-casein
PDZ domain deletion mutant, Hill constant 1.5, presence of inhibitor of apoptosis domain BIR3, 37°C, pH 7.8
-
0.62
beta-casein
PDZ domain deletion mutant, Hill constant 1.4, presence of inhibitor of apoptosis domain BIR2, 37°C, pH 7.8
-
0.8
beta-casein
PDZ domain deletion mutant, Hill constant 1.5, presence of inhibitor of apoptosis protein, 37°C, pH 7.8
-
1.29
beta-casein
mutant comprising N-terminal and serine protease domains, pH 8.0, 37°C
-
3.1
beta-casein
wild-type, Hill constant 1.8, presence of inhibitor of apoptosis domain BIR3, 37°C, pH 7.8
-
3.8
beta-casein
wild-type, Hill constant 1.6, presence of inhibitor of apoptosis domain BIR2, 37°C, pH 7.8
-
4.7
beta-casein
wild-type, Hill constant 1.5, presence of inhibitor of apoptosis protein, 37°C, pH 7.8
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
peptide derived from type III collagen alpha1 C-propeptide does not activate nor significantly bind to HtrA2 as compared to HtrA1
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 55
-
enzyme activity rapidly increases with temperature and it drastically decreases at and above 60°C, no significant change in secondary structure from 25-70 °C or in the oligomeric size between 25-55 °C, but significant change in tertiary level from 25-60 °C
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
cerebral plaques in the brains of patients with Alzheimer´s disease
platelets contain the pro-apoptotic proteins Omi/HtrA2 and Smac/Diablo, as well as their target, the X-linked inhibitor of apoptosis XIAP
-
stem sections and cortical slices from patients with pathologically confirmed idiopathic Parkinson's disease
increased interaction between HtrA2 and vimentin in human primary neurons upon stress stimuli
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
halo of Lewy bodies from patients with pathologically confirmed idiopathic Parkinson's disease
-
-
HtrA2 released from the mitochondrion to the cytoplasm during apoptosis in response to oxidative stress
N-truncated form is released into the cytosol upon apoptotic stimuli
-
Omi/HtrA2 relocates from mitochondria to the cytosol in lung adenocarcinoma cell line A549 under serum withdrawal
Omi/HtrA2 and Smac/Diablo are released from mitochondria into the platelet cytosol together with cytochrome c after induction of apoptosis by theCa2+ ionophore A23187 or the BH3 mimetic ABT-737, and to a lesser extent, after platelet stimulation with collagen and thrombin
-
-
652327, 667167, 667405, 667757, 668700, 669260, 669278, 669282, 687539, 689124, 689287, 689289, 695598, 697488, 697749, 699486, 700569, 700949, 709955, 710093
-
extramitochondrially expressed enzyme induces atypical cell death
-
mature protein is released form the mitochondria into the cytosol during aopotosis
-
mitochondria also contain processed Omi which, following apoptotic insult, translocates to the cytosol
-
normally expression of HtrA2, enzyme does not leave the mitochondria upon the TNF-alpha + zVAD-induced cell death in neutrophils
-
predominant localisation, enlarged mitochondria with disorganized cristae in mutant cells
-
amyloid precursor protein is partly colocalized with HtrA2 in the mitochondria
-
intermembrane space, HtrA2/Omi is required for mitochondrial homeostasis
-
immunostaining and confocal microscopy shows that Omi/HtrA2 is located primarily in the mitochondria of lung adenocarcinoma cell line A549
-
S-nitrosoglutathione treatment induces redistribution of Omi/HtrA2 from cytoplasm to mitochondria in endothelial cells
Omi/HtrA2 and Smac/Diablo are released from mitochondria into the platelet cytosol together with cytochrome c after induction of apoptosis by theCa2+ ionophore A23187 or the BH3 mimetic ABT-737, and to a lesser extent, after platelet stimulation with collagen and thrombin
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
-
in Omi/HtrA2 silenced human HeLa elongated mitochondria are found by live cell imaging. Electron microscopy confirm the mitochondrial morphology alterations and show abnormal cristae structure. Examining the levels of proteins involved in mitochondrial fusion, a selective up-regulation of optic atrophy protein 1 is shown
malfunction
-
loss of mitochondrial Omi/HtrA2 is associated with S-nitrosoglutathione-induced apoptosis in human endothelial cells
physiological function
-
HtrA2 has a moderate ability to delay the aggregation of citrate synthase in vitro. Additionally, using electron microscopy and nuclear magnetic resonance analyses, it is observed that HtrA2 significantly delays the aggregation of the Abeta1-42 peptide. The protease activity of HtrA2 and its PDZ domain are not essential for the delay of Abeta1-42 peptide aggregation
physiological function
-
HtrA2/Omi cleave Wilms'tumor suppressor protein WT1 which causes the removal of WT1 from its binding sites at gene promoters, leading to alterations in gene regulation that enhance apoptosis
physiological function
-
it is analyzed whether abnormal expression of HtrA2/Omi occurs in amyotrophic lateral sclerosis patients: abnormal accumulations of HtrA2/Omi may occur in several types of motor neuronal inclusions in the anterior horn from sporadic amyotrophic lateral sclerosis and Cu/Zn superoxide dismutase (SOD1)-related familial amyotrophic lateral sclerosis (FALS) cases, and that HtrA2/Omi may be associated with the pathogenesis of both types of amyotrophic lateral sclerosis
physiological function
-
Omi/HtrA2 interacts with thanatos-associated protein 5 in mammalian cells during apoptosis
physiological function
-
Omi/HtrA2 is released from mitochondria to the cytosol and is required for annexin A2 cleavage under apoptotic stimuli
physiological function
-
the HtrA2-mediated Parkin cleavage irreversibly disrupts Parkin-mediated synphilin-1 ubiquitination and autoubiquitination, indicating that HtrA2 may play a critical role in the Parkin-related pathway involved in the ubiquitin proteasome system
physiological function
-
proteolysis of Wilms' tumor suppressor 1 by HtrA2 causes the removal of WT1 from its binding sites at gene promoters, leading to alterations in gene regulation that enhance apoptosis
physiological function
-
HtrA2 acts as an apoptotic factor which targets inhibitors of apoptosis during apoptosis, and thereby enhances caspase activation and caspase-mediated cell death
physiological function
platelets contain the pro-apoptotic proteins Omi/HtrA2 and Smac/Diablo, as well as their target the X-linked inhibitor of apoptosis XIAP. Omi/HtrA2 and Smac/Diablo are released from mitochondria into the platelet cytosol together with cytochrome c after induction of apoptosis by theCa2+ ionophore A23187 or the BH3 mimetic ABT-737, and to a lesser extent, after platelet stimulation with collagen and thrombin
physiological function
silencing endogenous expression of HtrA2/Omi with siRNA results in aggregated endoplasmic reticulum stress and cell death. The expression level of HtrA2/Omi decreases with endoplasmic reticulum stress induction in 6-hydroxydopamine-treated SH-SY5Y cells
physiological function
during thermal activation, the PDZ domain changes its position versus the protease domain inside a subunit, including a prominent change affecting the L3 regulatory loop of the protease domain, and also changes its interactions with the protease domain of the adjacent subunit, specifically with its L1* regulatory loop containing the active site serine. The alpha5 helix of PDZ is involved in both, the intra- and intersubunit changes of interactions and seems to play an important role in HtrA2 activation
physiological function
HtrA2 under several different stress conditions induces cleavage of vimentin in wild-type as well as SH-SY5Y cells transfected with amyloid precursor protein with the Alzheimer disease-associated Swedish mutation. After stress treatment, inhibition of HtrA2 protease activity by the specific inhibitor, Ucf-101, reduces the cleavage of vimentin in wild-type cells
physiological function
The inhibition of HtrA2 by specific inhibitor UCF-101 or by shRNA reduces lipopolysaccharide-induced brain endothelial cell apoptosis, and results in significant improvement on lipopolysaccharide-induced blood-brain-barrier disruption as well as decreased occludin, claudin-5 and ZO-1 expressions. HtrA2 manipulates endothelial cell apoptosis by shifting into cytosol and inducing X-linked inhibitor of apoptosis protein (XIAP) degradation. UCF-101 administration or HtrA2 shRNA intervention attenuates the degradation of XIAP, poly-ADP-ribose polymerase (PARP), cleavage, and caspase-3 cleavage. UCF-101 partly prevents the mobilization of HtrA2 from the mitochondria to the cytosol after lipopolysaccharide intervention
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
110000
28000 - 44000
low molecular masses detected due to full-length HtrA2/Omi regions or amino acid residues that are very susceptible to a high degree of proteolytic events in Escherichia coli expression systems
35000
36000
50000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
the presence of the PDZ domain influences HtrA3 trimer formation. The C-terminal sequence of HtrA3 appears to have little effect on activity and oligomerization
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
proteolytic modification
-
133 N-terminal amino acids of the precursor protein are cleaved off
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
comparison of wild-type and mutan S276C. In wild-type, water molecule number 377 forms an interaction between side chains of S276 and I270* of the adjacent molecule. In mutant S276C, this water molecule is absent
structure of the HtrA3 protease domain together with the PDZ domain. The protein forms a trimer
structures of variant V226K/S306A and V325D. Upon binding of specific peptide ligand NH2-GWTMFWV-COOH, the PDZ domains open more dynamically in the wild type protease compared to the V226K mutant, whereas the movement is not observed in the V325D mutant. The movement relies on a PDZ vs. protease domain rotation which opens the protease domain-PDZ interface
to 1.65 A resolution. The catalytic triad in the HtrA2 wild-type structure is disrupted, with the nearest accessible H198 side chain atom positioned 5.9 A away from the carboxylate oxygen of D228 and separated from the hydroxyl of S306 by 7.4 A, requiring substantial rearrangements to reestablish a catalytically competent conformation. Dynamic protein motions are important to HtrA protease activity
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A141S
E292A
residue involved in most of the peptide interactions, about 30% of wild-type catalytic efficiency
E296A
residue involved in most of the peptide interactions, about 90% of wild-type catalytic efficiency
E425L
variant has an increased activity, especially at lower temperatures (25-30°C) and the highest affinity for the substrate and catalytic efficiency among all studied variants
F16D
residue involved in most of the peptide interactions, almost complete loss of catalytic activity
F303W
mutation does not cause significant destabilizing or stabilizing effects on the thermal denaturation
F331W
mutation in proease domain, mutation does not cause significant destabilizing or stabilizing effects on the thermal denaturation
G230A
residue involved in most of the peptide interactions, about 12% of wild-type catalytic efficiency
G399S
L367W
mutation does not cause significant destabilizing or stabilizing effects on the thermal denaturation
L377W
mutation in PDZ domain, mutation does not cause significant destabilizing or stabilizing effects on the thermal denaturation
N216A/S219A
residues involved in most of the peptide interactions, about 33% of wild-type catalytic efficiency
R337L
mutant has an increased activity at all temperatures tested, higher affinity for the substrate and a higher turnover rate
R432L
S142A
-
considerably less phosphorylated by p38gamma in vitro. Markedly lower protease activity than its acidic counterpart
S142D
S212A
-
mutant with abolished HtrA2/Omi phosphorylation by Akt. It retains its serine protease activity and induces more apoptosis as compared with wild-type HtrA2/Omi
S212D
-
mutant mimicking phosphorylation. It has lost the protease activity and fails to induce programmed cell death
S276C
S306A
S400A
-
considerably less phosphorylated by p38gamma in vitro. Markedly lower protease activity than its acidic counterpart
S400D
V226K
V226K E429L
salt link formation is no longer possible, the increase of activity observed for mutant V226K ceased to exist
V226W
mutation in proease domain, proteolytic activity similar to wild-type
V325D
V364W
mutation does not cause significant destabilizing or stabilizing effects on the thermal denaturation
Y361W
mutation in proease domain, proteolytic activity similar to wild-type
additional information
A141S
-
affects the enzymatic activity of the protease, associated with the development of Parkinsons disease
G399S
-
affects the enzymatic activity of the protease, associated with the development of Parkinsons disease
G399S
-
mutation in HtrA2 identified in patients with Parkinson's disease, ability of p38gamma to phosphorylate the peptide is decreased
R432L
variant has an increased activity with beta-casein and the peptide Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitro benzoic acid) at various temperatures
S142D
-
phospho-mimetic HtrA2-mutant, increases the basal ability of HtrA2 to cleave a fluorogenic substrate peptide by about 2fold
S142D
-
recombinant HtrA2 mutant, produced to determine whether HtrA2 phosphorylation affects its proteolytic activity
S276C
inactive. Mutation does not affect the oligomeric properties and maintains proper hydrogen bonding distances in the active-site triad residues
S306A
presence of a serine residue in position 306 favors an inactive conformation of H198, thereby perturbing the geometry of the active site
S400D
-
phospho-mimetic HtrA2-mutant, increases the basal ability of HtrA2 to cleave a fluorogenic substrate peptide by about 3fold
S400D
-
recombinant HtrA2 mutant, produced to determine whether HtrA2 phosphorylation affects its proteolytic activity
V226K
variant has an increased activity with beta-casein and the peptide Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitro benzoic acid) at various temperatures
additional information
-
truncated mutant lacking the putative mitochondrial localization motif in the first 33 amino acid residues shows distribution throughout the cell with no obvious concentration in the mitochondria
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
additional information
rs2231248, rs2241027 and rs2241028, HtrA2 variants
additional information
-
the activity to delay the aggreagtion is significantly enhanced when the PDZ domain is removed suggesting an inhibitory role for this domain on the activity
additional information
deletion mutant of the PDZ domain shows a catalytic efficiency 5.5fold less than intact trimeric HtrA2 and the apparent Km and co-operativity are also reduced. Deletion of the PDZ domain possibly affects the initial substrate binding process, allosteric modulation and cleavage, thereby leading to a decrease in co-operativity and catalytic efficiency
additional information
mutant comprising N-terminal and serine protease domains, residues 1210, displays about 20% of wild-type catalytic efficiency
additional information
a PDZ domain deletion mutant at 37°C shows 2.0fold higher cleavage activity assayed with beta-casein than wild-type
additional information
a variant lacking the N-terminal domain forms stable trimers while both the catalytic domain alone and the short natural isoform are monomeric. The protease domain with the PDZ domain removed and an N-terminally truncated short natural isoform are fully active at a wide range of temperatures and their substrate affinity is not impaired
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
upon an increase in temperature the HtrA2 structure relaxes, the PDZ-protease interface becomes more exposed to the solvent, and significant conformational changes involving both domains occur at and above 30 °C
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
rapid purification of full-length HtrA2/Omi as a GST fusion under non-denaturing conditions by selective binding to glutathione-Sepharose 4B beads
rapid purification of GST-HtrA2 delta 133 proteins on glutathione-Sepharose 4B beads
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
barely expressed full-length HtrA2/Omi as a GST fusion protein in Escherichia coli BL21
coexpression of Flag-tagged and Ndelta133 HtrA2 proteins and a myc-epitope-tagged GRIM-19 protein in MCF-7 cells. MCF-7 cells transfected with expression vectors coding for GFP-HtrA2 and GFP-HtrA2-S306A and GRIM-19
-
expressed in yeast as a bait protein in a two-hybrid assay and by transient transfection of Human embryonic kidney (HEK)-293 cells
-
expression in Escherichia coli
expression of GST-HtrA2 delta 133 proteins in Escherichia coli BL21 from GST-HTRA2 delta 133 WT, S306 and F149D constructs
-
HtrA2/Omi cDNA cloned into pEGFP-C3 at KpnI/XbaI sites. HeLa cells transfected with GFP-fused premature or mature HtrA2/Omi together with or without wild-type and constitutively active Akt. HEK-293 cells transfected with pcDNA3-Myc-HtrA2/Omi together with or without wild-type and constitutively active Akt
-
overexpression in Escherichia coli BL21 (DE3) and expressed in Saccharomyces cerevisiae EGY48/pLexA-hPag and their mutants
-
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
-
subcloned into pET28a and propageted in Escherichia coli DH5alpha, expressed in Escherichia coli BL21 (DE3) pLys, overexpression in K269 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
124 endometrial tissue specimens including 88 cancers and 36 normal endometria are analyzed. HtrA2 protein levels are significantly lower in endometrial cancer cells compared to normal cells
-
ablation of HtrA2 activity using RNAi in the human osteosarcoma U2OS cells prevents the cleavage of Wilms'tumor suppressor protein WT1 under apoptotic conditions
-
Omi/HtrA2 siRNA decreases the cleavage of annexin A2 lung epithelial adenocarcinoma cell A549 under both serum withdrawal and cisplatin treatment
-
S-nitrosoglutathione treatment significantly decreases mitochondrial Omi/HtrA2 content after 8 h of exposure in endothelial cells
-
S-nitrosoglutathione treatment significantly increases cytosolic Omi/HtrA2 content after 8 h of exposure in endothelial cells
-
the expression level of HtrA2/Omi decreases with endoplasmic reticulum stress induction in 6-hydroxydopamine-treated SH-SY5Y cells
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
amyloid beta, a pivotal factor implicated in the pathogenesis of Alzheimer´s disease interacts with HtrA2/Omi
medicine
additional information
-
a role for Omi-mediated processing of WTS in negative regulation of cell cycle progression at interphase. Omi protease is not necessarily required for cell death
medicine
-
heterozygous G399S mutation in Parkinson's disease patients, which is absent in healthy controls, a A141S polymorphism is associated with Parkinson's disease, both mutations result in defective activation of Omi/HtrA2 and mitochondrial dysfunction associated with altered mitochondrial morphology
medicine
-
way to limit renal injury by specifically inhibiting its proteolytic activity
medicine
-
critical role of HtrA2 in a cytokine-induced cell death response. Inhibition by a viral protein
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
medicine
-
link between HtrA2/Omi and Parkinsons disease or Alzheimers disease
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
medicine
-
HtrA2 is linked to cancer and neurodegeneration, like Alzheimers disease, Parkinsons disease, Huntingtons disease, and brain, kidney and myocardial ischemia, reperfusion
medicine
mutations of the OMI/HTRA2 gene are linked to Parkinsons disease
medicine
-
the function of Omi/HtrA2 is linked to selective vulnerability of striatal neurons in Huntingtons disease
medicine
-
the identification of the role of HtrA2 in neurodegeneration will lead to an improved understanding of the pathogenesis of Parkinsons disease
medicine
-
the relation between p73 and HtrA2 may help to understand the behavior of the p73 protein in the responses of cancer cells to chemotherapy
medicine
-
the study does not support a role of HtrA2 variants in the pathogenesis of Parkinsons disease
medicine
-
therapeutic interventions that inhibit HtrA2 expression, translocation, or protease activity may provide attractive therapeutics in the treatment of cardiovascular diseases
medicine
-
HtrA2/Omi is associated with the pathogenesis of amyotrophic lateral sclerosis
medicine
-
HtrA2-mediated proteolysis of WT1 may directly contribute to the effect of cytotoxic drugs warrants
medicine
HtrA2 under several different stress conditions induces cleavage of vimentin in wild-type as well as SH-SY5Y cells transfected with amyloid precursor protein with the Alzheimer disease-associated Swedish mutation. After stress treatment, inhibition of HtrA2 protease activity by the specific inhibitor, Ucf-101, reduces the cleavage of vimentin in wild-type cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Gray, C.W.; Ward, R.V.; Karran, E.; Turconi, S.; Rowles, A.; Viglienghi, D.; Southan, C.; Barton, A.; Fantom, K.G.; West, A.; Savopoulos, J.; Hassan, N.J.; Clinkenbeard, H.; Hanning, C.; Amegadzie, B.; Davis, J.B.; Dingwall, C.; Livi, G.P.; Creasy, C.L.
Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response
Eur. J. Biochem.
267
5699-5710
2000
Homo sapiens (O43464), Mus musculus (Q9JIY5)
Faccio, L.; Fusco, C.; Chen, A.; Martinotti, S.; Bonventre, J.V.; Zervos, A.S.
Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia
J. Biol. Chem.
275
2581-2588
2000
Homo sapiens (O43464)
Hegde, R.; Srinivasula, S.M.; Zhang, Z.; Wassell, R.; Mukattash, R.; Cilenti, L.; DuBois, G.; Lazebnik, Y.; Zervos, A.S.; Fernandes-Alnemri, T.; Alnemri, E.S.
Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase interaction
J. Biol. Chem.
277
432-438
2002
Homo sapiens
Martins, L.M.; Iaccarino, I.; Tenev, T.; Gschmeissner, S.; Totty, N.F.; Lemoine, N.R.; Savopoulos, J.; Gray, C.W.; Creasy, C.L.; Dingwall, C.; Downward, J.
The serine protease Omi/HtrA2 regulates apoptosis by binding XIAP through a reaper-like motif
J. Biol. Chem.
277
439-444
2002
Homo sapiens
Srinivasula, S.M.; Gupta, S.; Datta, P.; Zhang, Z.; Hegde, R.; Cheong, N.; Fernandes-Alnemri, T.; Alnemri, E.S.
Inhibitor of apoptosis proteins are substrates for the mitochondrial serine protease Omi/HtrA2
J. Biol. Chem.
278
31469-31472
2003
Homo sapiens
Martins, L.M.; Turk, B.E.; Cowling, V.; Borg, A.; Jarrell, E.T.; Cantley, L.C.; Downward, J.
Binding specificity and regulation of the serine protease and PDZ domains of HtrA2/Omi
J. Biol. Chem.
278
49417-49427
2003
Homo sapiens
Suzuki, Y.; Imai, Y.; Nakayama, H.; Takahashi, K.; Takio, K.; Takahashi, R.
A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death
Mol. Cell
8
613-621
2001
Homo sapiens
Savopoulos, J.W.; Carter, P.S.; Turconi, S.; Pettman, G.R.; Karran, E.H.; Gray, C.W.; Ward, R.V.; Jenkins, O.; Creasy, C.L.
Expression, purification, and functional analysis of the human serine protease HtrA2
Protein Expr. Purif.
19
227-234
2000
Homo sapiens (O43464), Homo sapiens
Cilenti, L.; Kyrizis, G.A.; Soundarapandian, M.M.; Stratico, V.; Yerkes, A.; Park, K.M.; Sheridan, A.M.; Alnemri, E.S.; Bonventre, J.V.; Zervos, A.S.
Omi/HtrA2 protease mediates cisplatin-induced cell death in renal cells
Am. J. Physiol. Renal Physiol.
288
F371-F379
2005
Homo sapiens, Mus musculus, Mus musculus C57BL6
Sekine, K.; Hao, Y.; Suzuki, Y.; Takahashi, R.; Tsuruo, T.; Naito, M.
HtrA2 cleaves Apollon and induces cell death by IAP-binding motif in Apollon-deficient cells
Biochem. Biophys. Res. Commun.
330
279-285
2005
Homo sapiens
Murwantoko, C.; Yano, M.; Ueta, Y.; Murasaki, A.; Kanda, H.; Oka, C.; Kawaichi, M.
Binding of proteins to the PDZ domain regulates proteolytic activity of HtrA1 serine protease
Biochem. J.
381
895-904
2004
Homo sapiens
Zhang, X.; Chang, Z
Temperature dependent protease activity and structural properties of human HtrA2 protease
Biochemistry (Moscow)
69
687-692
2004
Homo sapiens
Suzuki, Y.; Takahashi-Niki, K.; Akagi, T.; Hashikawa, T.; Takahashi, R.
Mitochondrial protease Omi/HtrA2 enhances caspase activation through multiple pathways
Cell Death Differ.
11
208-216
2004
Homo sapiens
Blink, E.; Maianski, N.A.; Alnemri, E.S.; Zervos, A.S.; Roos, D.; Kuijpers, T.W.
Intramitochondrial serine protease activity of Omi/HtrA2 is required for caspase-independent cell death of human neutrophils
Cell Death Differ.
11
937-939
2004
Homo sapiens
Nam, M.K.; Seong, Y.M.; Park, H.J.; Choi, J.Y.; Kang, S.; Rhim, H.
The homotrimeric structure of HtrA2 is indispensable for executing its serine protease activity
Exp. Mol. Med.
38
26-43
2006
Homo sapiens
Hong, S.K.; Cha, M.K.; Kim, I.H.
Specific protein interaction of human Pag with Omi/HtrA2 and the activation of the protease activity of Omi/HtrA2
Free Radic. Biol. Med.
40
275-284
2006
Homo sapiens
Strauss, K.M.; Martins, L.M.; Plun-Favreau, H.; Marx, F.P.; Kautzmann, S.; Berg, D.; Gasser, T.; Wszolek, Z.; Mueller, T.; Bornemann, A.; Wolburg, H.; Downward, J.; Riess, O.; Schulz, J.B.; Krueger, R.
Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease
Hum. Mol. Genet.
14
2099-2111
2005
Homo sapiens
Seong, Y.M.; Choi, J.Y.; Park, H.J.; Kim, K.J.; Ahn, S.G.; Seong, G.H.; Kim, I.K.; Kang, S.; Rhim, H.
Autocatalytic processing of HtrA2/Omi is essential for induction of caspase-dependent cell death through antagonizing XIAP
J. Biol. Chem.
279
37588-37596
2004
Bos taurus, Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
Gupta, S.; Singh, R.; Datta, P.; Zhang, Z.; Orr, C.; Lu, Z.; Dubois, G.; Zervos, A.S.; Meisler, M.H.; Srinivasula, S.M.; Fernandes-Alnemri, T.; Alnemri, E.S.
The C-terminal tail of presenelin regulates Omi/HtrA2 protease activity
J. Biol. Chem.
279
45844-45854
2004
Homo sapiens
Trencia, A.; Fiory, F.; Maitan, M.A.; Vito, P.; Barbagallo, A.P.; Perfetti, A.; Miele, C.; Ungaro, P.; Oriente, F.; Cilenti, L.; Zervos, A.S.; Formisano, P.; Beguinot, F.
Omi/HtrA2 promotes cell death by binding and degrading the anti-apoptotic protein ped/pea-15
J. Biol. Chem.
279
46566-46572
2004
Homo sapiens
Liu, M.L.; Liu, M.J.; Kim, J.M.; Kim, H.J.; Kim, J.H.; Hong, S.T.
HtrA2 interacts with A beta peptide but does not directly alter its production or degradation
Mol. Cell
20
83-89
2005
Homo sapiens
Park, H.J.; Seong, Y.M.; Choi, J.Y.; Kang, S.; Rhim, H.
Alzheimer's disease-associated amyloid beta interacts with the human serine protease HtrA2/Omi
Neurosci. Lett.
357
63-67
2004
Homo sapiens (Q92743), Homo sapiens
Seong, Y.M.; Park, H.J.; Seong, G.H.; Choi, J.Y.; Yoon, S.J.; Min, B.R.; Kang, S.; Rhim, H.
N-terminal truncation circumvents proteolytic degradation of the human HtrA2/Omi serine protease in Escherichia coli: rapid purification of a proteolytically active HtrA2/Omi
Protein Expr. Purif.
33
200-208
2004
Homo sapiens (O43464), Homo sapiens, Mus musculus
Vande Walle, L.; Lamkanfi, M.; Vandenabeele, P.
The mitochondrial serine protease HtrA2/Omi: an overview
Cell Death Differ.
15
453-460
2008
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
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
J. Biol. Chem.
281
34277-34287
2006
Homo sapiens, Mus musculus
Yang, L.; Sun, M.; Sun, X.M.; Cheng, G.Z.; Nicosia, S.V.; Cheng, J.Q.
Akt attenuation of the serine protease activity of HtrA2/Omi through phosphorylation of serine 212
J. Biol. Chem.
282
10981-10987
2007
Homo sapiens
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
Nat. Cell Biol.
9
1243-1252
2007
Homo sapiens, Mus musculus
Kuninaka, S.; Iida, S.I.; Hara, T.; Nomura, M.; Naoe, H.; Morisaki, T.; Nitta, M.; Arima, Y.; Mimori, T.; Yonehara, S.; Saya, H.
Serine protease Omi/HtrA2 targets WARTS kinase to control cell proliferation
Oncogene
26
2395-2406
2007
Homo sapiens, Mus musculus, synthetic construct
Ma, X.; Kalakonda, S.; Srinivasula, S.M.; Reddy, S.P.; Platanias, L.C.; Kalvakolanu, D.V.
GRIM-19 associates with the serine protease HtrA2 for promoting cell death
Oncogene
26
4842-4849
2007
Homo sapiens
Plun-Favreau, H.; Gandhi, S.; Wood-Kaczmar, A.; Deas, E.; Yao, Z.; Wood, N.W.
What have PINK1 and HtrA2 genes told us about the role of mitochondria in Parkinsons disease?
Ann. N. Y. Acad. Sci.
1147
30-36
2008
Homo sapiens
Bhuiyan, M.S.; Fukunaga, K.
Activation of HtrA2, a mitochondrial serine protease mediates apoptosis: current knowledge on HtrA2 mediated myocardial ischemia/reperfusion injury
Cardiovasc. ther.
26
224-232
2008
Homo sapiens
Marabese, M.; Mazzoletti, M.; Vikhanskaya, F.; Broggini, M.
HtrA2 enhances the apoptotic functions of p73 on bax
Cell Death Differ.
15
849-858
2008
Homo sapiens
Narkiewicz, J.; Klasa-Mazurkiewicz, D.; Zurawa-Janicka, D.; Skorko-Glonek, J.; Emerich, J.; Lipinska, B.
Changes in mRNA and protein levels of human HtrA1, HtrA2 and HtrA3 in ovarian cancer
Clin. Biochem.
41
561-569
2008
Homo sapiens
Bhuiyan, M.S.; Fukunaga, K.
Mitochondrial serine protease HtrA2/Omi as a potential therapeutic target
Curr. Drug Targets
10
372-383
2009
Homo sapiens
Inagaki, R.; Tagawa, K.; Qi, M.L.; Enokido, Y.; Ito, H.; Tamura, T.; Shimizu, S.; Oyanagi, K.; Arai, N.; Kanazawa, I.; Wanker, E.E.; Okazawa, H.
Omi /HtrA2 is relevant to the selective vulnerability of striatal neurons in Huntingtons disease
Eur. J. Neurosci.
28
30-40
2008
Homo sapiens, Mus musculus, Rattus norvegicus
Simon-Sanchez, J.; Singleton, A.B.
Sequencing analysis of OMI/HTRA2 shows previously reported pathogenic mutations in neurologically normal controls
Hum. Mol. Genet.
17
1988-1993
2008
Homo sapiens (O43464)
Bogaerts, V.; Nuytemans, K.; Reumers, J.; Pals, P.; Engelborghs, S.; Pickut, B.; Corsmit, E.; Peeters, K.; Schymkowitz, J.; De Deyn, P.P.; Cras, P.; Rousseau, F.; Theuns, J.; Van Broeckhoven, C.
Genetic variability in the mitochondrial serine protease HTRA2 contributes to risk for Parkinson disease
Hum. Mutat.
29
832-840
2008
Homo sapiens (O43464), Homo sapiens
Han, C.; Nam, M.K.; Park, H.J.; Seong, Y.M.; Kang, S.; Rhim, H.
Tunicamycin-induced ER stress upregulates the expression of mitochondrial HtrA2 and promotes apoptosis through the cytosolic release of HtrA2
J. Microbiol. Biotechnol.
18
1197-1202
2008
Homo sapiens
Ross, O.A.; Soto, A.I.; Vilarino-Gueell, C.; Heckman, M.G.; Diehl, N.N.; Hulihan, M.M.; Aasly, J.O.; Sando, S.; Gibson, J.M.; Lynch, T.; Krygowska-Wajs, A.; Opala, G.; Barcikowska, M.; Czyzewski, K.; Uitti, R.J.; Wszolek, Z.K.; Farrer, M.J.
Genetic variation of Omi/HtrA2 and Parkinsons disease
Parkinsonism Relat. Disord.
14
539-543
2008
Homo sapiens
McCormick, A.L.; Roback, L.; Mocarski, E.S.
HtrA2/Omi terminates cytomegalovirus infection and is controlled by the viral mitochondrial inhibitor of apoptosis (vMIA)
PLoS Pathog.
4
e1000063
2008
Homo sapiens (O43464)
Krick, S.; Shi, S.; Ju, W.; Faul, C.; Tsai, S.Y.; Mundel, P.; Boettinger, E.P.
Mpv17l protects against mitochondrial oxidative stress and apoptosis by activation of Omi/HtrA2 protease
Proc. Natl. Acad. Sci. USA
105
14106-14111
2008
Chlorocebus aethiops, Homo sapiens, Mus musculus
Balakrishnan, M.P.; Cilenti, L.; Mashak, Z.; Popat, P.; Alnemri, E.S.; Zervos, A.S.
THAP5 is a human cardiac-specific inhibitor of cell cycle that is cleaved by the proapoptotic Omi/HtrA2 protease during cell death
Am. J. Physiol. Heart Circ. Physiol.
297
H643-H653
2009
Homo sapiens
Park, H.M.; Kim, G.Y.; Nam, M.K.; Seong, G.H.; Han, C.; Chung, K.C.; Kang, S.; Rhim, H.
The serine protease HtrA2/Omi cleaves Parkin and irreversibly inactivates its E3 ubiquitin ligase activity
Biochem. Biophys. Res. Commun.
387
537-542
2009
Homo sapiens, Mus musculus
Kieper, N.; Holmstroem, K.M.; Ciceri, D.; Fiesel, F.C.; Wolburg, H.; Ziviani, E.; Whitworth, A.J.; Martins, L.M.; Kahle, P.J.; Krueger, R.
Modulation of mitochondrial function and morphology by interaction of Omi/HtrA2 with the mitochondrial fusion factor OPA1
Exp. Cell Res.
316
1213-1224
2010
Drosophila melanogaster, Homo sapiens, Mus musculus
Kooistra, J.; Milojevic, J.; Melacini, G.; Ortega, J.
A new function of human HtrA2 as an amyloid-beta oligomerization inhibitor
J. Alzheimers Dis.
17
281-294
2009
Homo sapiens
Wang, C.Y.; Lin, Y.S.; Su, W.C.; Chen, C.L.; Lin, C.F.
Glycogen synthase kinase-3 and Omi/HtrA2 induce annexin A2 cleavage followed by cell cycle inhibition and apoptosis
Mol. Biol. Cell
20
4153-4161
2009
Homo sapiens
Hartkamp, J.; Carpenter, B.; Roberts, S.G.
The Wilms tumor suppressor protein WT1 is processed by the serine protease HtrA2/Omi
Mol. Cell
37
159-171
2010
Homo sapiens, Mus musculus
Kawamoto, Y.; Ito, H.; Kobayashi, Y.; Suzuki, Y.; Akiguchi, I.; Fujimura, H.; Sakoda, S.; Kusaka, H.; Hirano, A.; Takahashi, R.
HtrA2/Omi-immunoreactive intraneuronal inclusions in the anterior horn of patients with sporadic and SOD1 mutant amyotrophic lateral sclerosis
Neuropathol. Appl. Neurobiol.
36
331-344
2010
Homo sapiens
Narkiewicz, J.; Lapinska-Szumczyk, S.; Zurawa-Janicka, D.; Skorko-Glonek, J.; Emerich, J.; Lipinska, B.
Expression of human HtrA1, HtrA2, HtrA3 and TGF-beta1 genes in primary endometrial cancer
Oncol. Rep.
21
1529-1537
2009
Homo sapiens
Essafi, A.; Hastie, N.D.
WT1 the oncogene: a tale of death and HtrA
Mol. Cell
37
153-155
2010
Homo sapiens
Liu, Q.B.; Liu, L.L.; Lu, Y.M.; Tao, R.R.; Huang, J.Y.; Shioda, N.; Moriguchi, S.; Fukunaga, K.; Han, F.; Lou, Y.J.
The induction of reactive oxygen species and loss of mitochondrial Omi/HtrA2 is associated with S-nitrosoglutathione-induced apoptosis in human endothelial cells
Toxicol. Appl. Pharmacol.
244
374-384
2010
Homo sapiens
Chien, J.
WT1 as a substrate of HtrA2: A potential pathway for therapeutic targeting by HtrA proteases
Future Oncol.
6
1233-1235
2010
Homo sapiens
Wysocka, M.; Wojtysiak, A.; Okonska, M.; Gruba, N.; Jarzab, M.; Wenta, T.; Lipinska, B.; Grzywa, R.; Sienczyk, M.; Rolka, K.; Lesner, A.
Design and synthesis of new substrates of HtrA2 protease
Anal. Biochem.
475
44-52
2015
Homo sapiens (O43464)
Zurawa-Janicka, D.; Jarzab, M.; Polit, A.; Skorko-Glonek, J.; Lesner, A.; Gitlin, A.; Gieldon, A.; Ciarkowski, J.; Glaza, P.; Lubomska, A.; Lipinska, B.
Temperature-induced changes of HtrA2(Omi) protease activity and structure
Cell Stress Chaperones
18
35-51
2013
Homo sapiens (O43464)
Singh, N.; DSouza, A.; Cholleti, A.; Sastry, G.M.; Bose, K.
Dual regulatory switch confers tighter control on HtrA2 proteolytic activity
FEBS J.
281
2456-2470
2014
Homo sapiens (O43464)
Luo, F.; Wei, L.; Sun, C.; Chen, X.; Wang, T.; Li, Y.; Liu, Z.; Chen, Z.; Xu, P.
HtrA2/Omi is involved in 6-OHDA-induced endoplasmic reticulum stress in SH-SY5Y cells
J. Mol. Neurosci.
47
120-127
2012
Homo sapiens (O43464), Homo sapiens
Bejugam, P.; Kuppili, R.; Singh, N.; Gadewal, N.; Chaganti, L.; Sastry, G.; Bose, K.
Allosteric regulation of serine protease HtrA2 through novel non-canonical substrate binding pocket
PLoS ONE
8
e55416
2013
Homo sapiens (O43464)
Winkler, J.; Rand, M.L.; Schmugge, M.; Speer, O.
Omi/HtrA2 and XIAP are components of platelet apoptosis signalling
Thromb. Haemost.
109
532-539
2013
Homo sapiens (O43464)
Wysocka, M.; Wojtysiak, A.; Okonska, M.; Gruba, N.; Jarzab, M.; Wenta, T.; Lipinska, B.; Grzywa, R.; Sienczyk, M.; Rolka, K.; Lesner, A.
Design and synthesis of new substrates of HtrA2 protease
Anal. Biochem.
475
44-52
2015
Homo sapiens (O43464)
Jarzab, M.; Wenta, T.; Zurawa-Janicka, D.; Polit, A.; Gieldon, A.J.; Wysocka, M.; Glaza, P.; Skorko-Glonek, J.; Ciarkowski, J.; Lesner, A.; Lipinska, B.
Intra- and intersubunit changes accompanying thermal activation of the HtrA2(Omi) protease homotrimer
Biochim. Biophys. Acta
1864
283-296
2016
Homo sapiens (O43464)
Wagh, A.R.; Bose, K.
Structural basis of inactivation of human counterpart of mouse motor neuron degeneration 2 mutant in serine protease HtrA2
Biosci. Rep.
38
BSR20181072
2018
Homo sapiens (O43464), Homo sapiens
Merski, M.; Moreira, C.; Abreu, R.M.; Ramos, M.J.; Fernandes, P.A.; Martins, L.M.; Pereira, P.J.B.; Macedo-Ribeiro, S.
Molecular motion regulates the activity of the mitochondrial serine protease HtrA2
Cell Death Dis.
8
e3119
2017
Homo sapiens (O43464), Homo sapiens
Hu, Y.; Bi, Y.; Yao, D.; Wang, P.; Li, Y.
Omi/HtrA2 protease associated cell apoptosis participates in blood-brain barrier dysfunction
Front. Mol. Neurosci.
12
48
2019
Homo sapiens (O43464), Homo sapiens
Sun, M.L.; Sun, L.M.; Wang, Y.Q.
Peptide selectivity between the PDZ domains of human pregnancy-related serine proteases (HtrA1, HtrA2, HtrA3, and HtrA4) can be reshaped by different halogen probes
J. Mol. Recognit.
31
e2698
2018
Homo sapiens (O43464)
Lucotte, B.; Tajhizi, M.; Alkhatib, D.; Samuelsson, E.; Wiehager, B.; Schedin-Weiss, S.; Sundstrom, E.; Winblad, B.; Tjernberg, L.; Behbahani, H.
Stress conditions increase vimentin cleavage by Omi/HtrA2 protease in human primary neurons and differentiated neuroblastoma cells
Mol. Neurobiol.
52
1077-1092
2015
Homo sapiens (O43464), Homo sapiens
Glaza, P.; Osipiuk, J.; Wenta, T.; Zurawa-Janicka, D.; Jarzab, M.; Lesner, A.; Banecki, B.; Skorko-Glonek, J.; Joachimiak, A.; Lipinska, B.
Structural and functional analysis of human HtrA3 protease and its subdomains
PLoS ONE
10
e0131142
2015
Homo sapiens (P83110)
EXTERNAL LINKS (specific for EC-Number 3.4.21.108)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
