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Information on EC 3.4.21.108 - HtrA2 peptidase
for references in articles please use BRENDA:EC3.4.21.108
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EC Tree 3 Hydrolases
3.4 Acting on peptide bonds (peptidases)
3.4.21 Serine endopeptidases
3.4.21.108 HtrA2 peptidase
IUBMB Comments
This enzyme is upregulated in mammalian cells in response to stress induced by both heat shock and tunicamycin treatment . It can induce apoptosis in a caspase-independent manner through its peptidase activity and in a caspase-dependent manner by disrupting the interaction between caspase and the inhibitor of apoptosis (IAP) . Belongs in peptidase family S1C.
The enzyme appears in viruses and cellular organisms
- 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
Reaction Schemes
showcleavage 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
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
high temperature requirement A2
high temperature requirement A2 protease
high temperature requirement protease A2
high temperature requirement protein A2
high-temperature requirement A2
HtrA2
HtrA2 protease
HtrA2 serine protease
HtrA2/Omi
Nma11p
Omi
Omi protease
Omi/HtrA2
Omi/HtrA2 protease
pro-apoptotic serine protease
serine protease
serine protease HtrA2
serine protease HtrA2/Omi
serine protease Omi/HtrA2
HtrA2
-
-
HtrA2
-
-
HtrA2 protease
-
-
-
-
HtrA2/Omi
-
-
HtrA2/Omi
-
-
Omi/HtrA2
-
-
serine protease
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cleavage of C-N-linkage
hydrolysis of peptide bond
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CAS REGISTRY NUMBER
COMMENTARY
204655-80-1
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
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
?
-
Substrates: -
Products: -
Products: -
?
(7-methoxycoumarin-4-yl)acetyl-IRRVSYSF(Dnp)KK + H2O
?
-
Substrates: best substrate
Products: -
Products: -
?
(7-methoxycoumarin-4-yl)acetyl-VTLCAVPS(Dnp)KK + H2O
?
-
Substrates: cleavage occurs between cysteine and alanine
Products: -
Products: -
?
(7-methoxycoumarin-4-yl)AIRRVSYSF-(5-amino-2-nitro)benzamide + H2O
?
Substrates: -
Products: -
Products: -
?
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
Substrates: -
Products: -
Products: -
?
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
Substrates: -
Products: -
Products: -
?
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
Substrates: -
Products: -
Products: -
?
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
Substrates: -
Products: -
Products: -
?
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
Substrates: -
Products: -
Products: -
?
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
Substrates: -
Products: -
Products: -
?
35S-beta-casein + H2O
?
-
Substrates: C-terminus of presenilin-1 interacts the PDZ domain of with Omi/HtrA2, increasing its activity
Products: -
Products: -
?
A beta 40
?
-
Substrates: HtrA2/Omi binds preferentially to the short form of A beta peptides, the enzyme does not perform degradation by direct hydrolysis
Products: -
Products: -
?
A beta 42
?
-
Substrates: HtrA2/Omi binds poorly to A beta 42, the enzyme does not perform degradation by direct hydrolysis
Products: -
Products: -
?
alpha-secretase peptide
?
-
Substrates: HtrA2/Omi does not perform degradation by direct hydrolysis
Products: -
Products: -
?
amyloid precursor protein-like protein 1 + H2O
?
-
Substrates: processed into two major fragments of 65 and 67 kDa
Products: -
Products: -
?
amyloid precursor protein-like protein 2 + H2O
?
-
Substrates: processed into cleaved fragments of 103 and 109 kDa
Products: -
Products: -
?
beta-casein
?
-
Substrates: 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
Products: -
Products: -
?
beta-secretase peptide
?
-
Substrates: HtrA2/Omi does not perform degradation by direct hydrolysis
Products: -
Products: -
?
c-inhibitor of apoptosis protein1 + H2O
?
-
Substrates: C-terminus of presenilin-1 interacts with the PDZ domain of Omi/HtrA2, increasing its activity
Products: -
Products: -
?
c-inhibitor of apoptosis protein2 + H2O
?
-
Substrates: C-terminus of presenilin-1 interacts with the PDZ domain of Omi/HtrA2, increasing its activity
Products: -
Products: -
?
cFLIP + H2O
?
Substrates: cellular FLICE like inhibitory protein
Products: -
Products: -
?
FLIP + H2O
?
-
Substrates: Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein
Products: -
Products: -
?
gamma-secretase peptide
?
-
Substrates: 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
Products: -
Products: -
?
HS1-associated protein X-1 + H2O
?
-
Substrates: HtrA2/Omi-mediated degradation of HS1-associated protein X-1 correlates with extensive cell death in response to etoposide, cisplatin and H2O2
Products: -
Products: -
?
PED-PEA 15 + H2O
?
-
Substrates: death effector domain-containing protein
Products: -
Products: -
?
ped/pea-15
?
-
Substrates: HtrA2 is a specific interactor of the ped/pea-15 death effector domain and leads to its degradation
Products: -
Products: -
?
protein cIAP1 + H2O
?
-
Substrates: best substrate, preferred cleavage sites are after Thr4, Asn133 and Leu161
Products: -
Products: -
?
receptor-interacting protein 1 + H2O
?
-
Substrates: the HtrA2/Omi cleavage site receptor-interacting protein 1 is mapped to the intermediate domain and the corresponding N- and C-terminal fragments are impaired in their ability to activate nuclear factor-kappaB, c-Jun N-terminal kinase and p38 mitogen-activated protein kinase
Products: -
Products: -
?
reduced bovine serum albumin
?
-
Substrates: HtrA2-Opt peptides stimulate the delta N-HtrA1 protease activity more than 3fold
Products: -
Products: -
?
thanatos-associated protein 5 (THAP5) + H2O
?
-
Substrates: 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
Products: -
Products: -
?
ubiquitin carboxyl-terminal hydrolase L1 + H2O
?
-
Substrates: natural substrate for HtrA2 in the apoptotic pathway. HtrA2 directly cleaves UCH-L1 and inhibits its hydrolase activity
Products: -
Products: -
?
unidentified substrate + H2O
?
-
Substrates: its cleavage by Omi/HtrA2 leads to permeabilization of the mitochondria outer membrane and release of chytochrome c followed by enhanced caspase activation
Products: -
Products: -
?
WARTS kinase + H2O
?
-
Substrates: WARTS, WTS, large tumor-suppressor 1 mitotic kinase
Products: -
Products: -
?
X-linked inhibitor of apoptosis protein
?
-
Substrates: HtrA2 promotes degradation of the X-linked inhibitor of apoptosis protein followed by subsequent caspase activation
Products: -
Products: -
?
Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide) + H2O
?
Substrates: -
Products: -
Products: -
?
Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide) + H2O
?
Substrates: -
Products: -
Products: -
?
amyloid precursor protein + H2O
?
-
Substrates: 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
Products: -
Products: -
?
Apollon + H2O
?
-
Substrates: 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
Products: -
Products: -
?
beta-casein + H2O
?
-
Substrates: 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
Products: -
Products: -
?
beta-casein + H2O
?
-
Substrates: cleaved to approximately 50% by GST-HtrA2 after a cleavage reaction for 1 h
Products: -
Products: -
?
Bir1p + H2O
?
-
Substrates: inhibitor of apoptosis proteins (IAP) Bir1p is a substrate for Nma11p, which is the yeast homologue of the human OMI/HtrA2, Bir1p physically interacts with the N-terminal HtrA-like repeat of Nma11p
Products: -
Products: -
?
Bir1p + H2O
?
-
Substrates: inhibitor of apoptosis proteins (IAP) Bir1p is a substrate for Nma11p, which is the yeast homologue of the human OMI/HtrA2, Bir1p physically interacts with the N-terminal HtrA-like repeat of Nma11p
Products: -
Products: -
?
GRIM-19 + H2O
?
-
Substrates: gene associated with retinoic and interferon-induced mortality 19, also known as NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 (NDUFA13). The cleavage sites are found between 19I-20D, 40I-41G, 49S-50I, 68R-69I, K97-100D and 108E-109S residues
Products: -
Products: -
?
inhibitor of apoptosis + H2O
?
-
Substrates: enzyme cleaves various IAPs
Products: -
Products: -
?
parkin + H2O
?
-
Substrates: using cleavage and binding assays, it is demonstrated that HtrA2 specifically binds to and directly cleaves the E3 ubiquitin ligase Parkin
Products: -
Products: -
?
parkin + H2O
?
-
Substrates: HtrA2/Omi cleaves E3 ubiquitin ligase Parkin
Products: -
Products: -
?
Wilms' tumor suppressor 1 + H2O
?
-
Substrates: 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
Products: -
Products: -
?
Wilms' tumor suppressor 1 + H2O
?
-
Substrates: 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
Products: -
Products: -
?
Wilms' tumor suppressor protein WT1 + H2O
?
-
Substrates: 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
Products: -
Products: -
?
X-linked inhibitor of apoptosis protein + H2O
?
-
Substrates: -
Products: -
Products: -
?
X-linked inhibitor of apoptosis protein + H2O
?
-
Substrates: BIR2
Products: -
Products: -
?
X-linked inhibitor of apoptosis protein + H2O
?
-
Substrates: autocatalytically processing of HtrA2 to the 36-kDa protein fragment, which is required for the cytochrome c-dependent caspase activation, promoting apoptotic cell death
Products: -
Products: -
?
X-linked inhibitor of apoptosis protein + H2O
?
-
Substrates: C-terminus of presenilin-1 interacts with the PDZ domain of Omi/HtrA2, increasing its activity
Products: -
Products: -
?
X-linked inhibitor of apoptosis protein + H2O
?
-
Substrates: homotrimeric structure of enzyme is required for executing its activity
Products: -
Products: -
?
X-linked inhibitor of apoptosis protein + H2O
?
-
Substrates: Omi/HtrA2 cleaves as well as directly binds and inactivates X-linked inhibitor of apoptosis protein to promote caspase activation
Products: -
Products: -
?
X-linked inhibitor of apoptosis protein + H2O
?
-
Substrates: -
Products: -
Products: -
?
X-linked inhibitor of apoptosis protein + H2O
?
-
Substrates: -
Products: -
Products: -
?
X-linked inhibitor of apoptosis protein + H2O
?
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: no cleavage of STDGGV-para-nitroaniline and SKAKGGEEPLPEGV-para-nitroaniline
Products: -
Products: -
?
additional information
?
-
Substrates: cleavage of DIAP1 between the BIR1 and BIR2 domain and further degradation of BIR1
Products: -
Products: -
?
additional information
?
-
-
Substrates: Omi can degrade inhibitor of apoptosis proteins
Products: -
Products: -
?
additional information
?
-
-
Substrates: can promote caspase activation and cell death apoptosis
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: role in apoptosis, amino-terminal IAP interaction motif displaces IAPs from caspases, leading to enhanced caspase activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: role in apoptosis, binds to XIAP-binding protein
Products: -
Products: -
?
additional information
?
-
Substrates: role in apoptosis, degradation of aberrantly folded proteins during conditions of cellular stress
Products: -
Products: -
?
additional information
?
-
-
Substrates: role in apoptosis, degradation of aberrantly folded proteins during conditions of cellular stress
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: does not bind the reversed control peptide A beta 41-1 and peptide H2-Opt
Products: -
Products: -
?
additional information
?
-
-
Substrates: beta-synuclein is not cleaved by HtrA2
Products: -
Products: -
?
additional information
?
-
-
Substrates: HtrA2 cleaves p73alpha in the C-terminal portion
Products: -
Products: -
?
additional information
?
-
-
Substrates: degradation of inhibitor of apoptosis proteins, IAPs
Products: -
Products: -
?
additional information
?
-
-
Substrates: co-immunoprecipitation show direct interaction of Omi/HtrA2 with optic atrophy protein 1 (OPA1)
Products: -
Products: -
?
additional information
?
-
-
Substrates: HtrA2 fails to cleave the Wilms' tumor suppressor 1 cofactors Par-4 and BASP1
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: induces cell death in a caspase-dependent manner
Products: -
Products: -
?
additional information
?
-
-
Substrates: role in apoptosis, mice with mutant HtrA2/Omi suffer from neurodegenerative disease due to progressive mitochondrial damage, mutant enzyme is proteolytically inactive but can bind to IAPs
Products: -
Products: -
?
additional information
?
-
Substrates: loss of enzyme activity causes neuromuscular disorder
Products: -
Products: -
?
additional information
?
-
-
Substrates: loss of enzyme activity causes neuromuscular disorder
Products: -
Products: -
?
additional information
?
-
-
Substrates: role in apoptosis, mice with mutant HtrA2/Omi suffer from neurodegenerative disease due to progressive mitochondrial damage, mutant enzyme is proteolytically inactive but can bind to IAPs
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme does not affect monomeric alpha-synuclein
Products: -
Products: -
-
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
thanatos-associated protein 5 (THAP5) + H2O
?
-
Substrates: 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
Products: -
Products: -
?
ubiquitin carboxyl-terminal hydrolase L1 + H2O
?
-
Substrates: natural substrate for HtrA2 in the apoptotic pathway. HtrA2 directly cleaves UCH-L1 and inhibits its hydrolase activity
Products: -
Products: -
?
parkin + H2O
?
-
Substrates: using cleavage and binding assays, it is demonstrated that HtrA2 specifically binds to and directly cleaves the E3 ubiquitin ligase Parkin
Products: -
Products: -
?
parkin + H2O
?
-
Substrates: HtrA2/Omi cleaves E3 ubiquitin ligase Parkin
Products: -
Products: -
?
Wilms' tumor suppressor 1 + H2O
?
-
Substrates: 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
Products: -
Products: -
?
Wilms' tumor suppressor 1 + H2O
?
-
Substrates: 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
Products: -
Products: -
?
Wilms' tumor suppressor protein WT1 + H2O
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: cleavage of DIAP1 between the BIR1 and BIR2 domain and further degradation of BIR1
Products: -
Products: -
?
additional information
?
-
-
Substrates: can promote caspase activation and cell death apoptosis
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: role in apoptosis, amino-terminal IAP interaction motif displaces IAPs from caspases, leading to enhanced caspase activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: role in apoptosis, binds to XIAP-binding protein
Products: -
Products: -
?
additional information
?
-
Substrates: role in apoptosis, degradation of aberrantly folded proteins during conditions of cellular stress
Products: -
Products: -
?
additional information
?
-
-
Substrates: role in apoptosis, degradation of aberrantly folded proteins during conditions of cellular stress
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: HtrA2 cleaves p73alpha in the C-terminal portion
Products: -
Products: -
?
additional information
?
-
-
Substrates: degradation of inhibitor of apoptosis proteins, IAPs
Products: -
Products: -
?
additional information
?
-
-
Substrates: co-immunoprecipitation show direct interaction of Omi/HtrA2 with optic atrophy protein 1 (OPA1)
Products: -
Products: -
?
additional information
?
-
-
Substrates: HtrA2 fails to cleave the Wilms' tumor suppressor 1 cofactors Par-4 and BASP1
Products: -
Products: -
?
additional information
?
-
-
Substrates: induces cell death in a caspase-dependent manner
Products: -
Products: -
?
additional information
?
-
-
Substrates: role in apoptosis, mice with mutant HtrA2/Omi suffer from neurodegenerative disease due to progressive mitochondrial damage, mutant enzyme is proteolytically inactive but can bind to IAPs
Products: -
Products: -
?
additional information
?
-
Substrates: loss of enzyme activity causes neuromuscular disorder
Products: -
Products: -
?
additional information
?
-
-
Substrates: loss of enzyme activity causes neuromuscular disorder
Products: -
Products: -
?
additional information
?
-
-
Substrates: role in apoptosis, mice with mutant HtrA2/Omi suffer from neurodegenerative disease due to progressive mitochondrial damage, mutant enzyme is proteolytically inactive but can bind to IAPs
Products: -
Products: -
?
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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
N-tosyllysine chloromethyl ketone
-
blocks ability of wild-type Omi to proteolyse WTS
siRNA
-
suppresses endogenous HtrA2, which results in almost 2030% reduction of C161 production
-
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
-
0.02 mM abrogates the death effect of the TNF-alpha + zVAD combination
ucf-101
-
treatment of lung epithelial adenocarcinoma cell A549 decreases the cleavage of annexin A2 under both serum withdrawal and cisplatin treatment
ucf-101
-
blocks protease activity of Omi, protects renal cells from cisplatin-induced cell death, mice treated with cisplatin and ucf-101 were more resistant to nephrotoxicy than animals treated with ciplatin alone
ucf-101
-
treatment of retinal epithelial cells with UCF-101 reduces the cytosolic translocation of HtrA2/Omi, attenuates caspase-3 activation, and decreases apoptosis
ucf-101
-
specific inhibitor of Omi/HtrA2. Reduces the number of TUNEL-positive cells, attenuates the X-linked inhibitor of apoptosis protein-breakdown and reduces the infarct size
ucf-101
-
specific inhibitor for Omi/HtrA2 protects against cerebral ischemia
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
-
additional information
-
ucf-101 fails to exert any additional protective effect in transfected cells
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
DKVLVVWAGQQ
-
full-length denatured alpha-amylase, as well as alpha-amylase fragments and the C-terminus of alpha-amylase, amplify DegP proteolysis
HAX-1
hematopoietic cell-specific protein 1-associated protein X-1, allosteric activator of the enzyme
-
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
-
GRIM-19
-
direct enhancement of HtrA2 activity in vitro. HtrA2-driven destruction of the antiapoptotic X-linked inhibitor of apoptosis protein is augmented
-
staurosporine
-
apoptotic stimulus to release 36-kDa protein fragment of HtrA2 and cytochrome c from the mitochondria to the cytosol
staurosporine
-
activates protease activity of Omi leading to cell death. Induces cell death in wild-type MEFs but not in caspase-9-deficient MEFs
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
-
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/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
-
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
-
additional information
-
apoptotic stimuli induce the activation of Omi and the consequent digestion of WTS by a caspase-independent mechanism
-
additional information
-
focal cerebral ischemia/reperfusion induces a mitochondrial up-regulation of Omi/HtrA2 and significantly increases cytosolic accumulation of Omi/HtrA2
-
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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
0.00074 - 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
0.000974
beta-casein
wild type enzyme, in the absence of activator peptide BIR2, pH and temperature not specified in the publication
-
0.00136
beta-casein
mutant enzyme P148A, in the presence of activator peptide BIR2, pH and 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 1.5, presence of inhibitor of apoptosis domain BIR3, 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
-
0.00175
beta-casein
mutant enzyme P148A, in the absence of activator peptide BIR2, pH and temperature not specified in the publication
-
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 2.8, 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 1.6, presence of inhibitor of apoptosis domain BIR2, 37°C, pH 7.8
-
0.00231
beta-casein
wild type enzyme, in the absence of activator peptide BIR2, pH and temperature not specified in the publication
-
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
-
0.00333
beta-casein
mutant enzyme F131A, in the presence of activator peptide BIR2, pH and temperature not specified in the publication
-
0.0035
beta-casein
mutant G230A, K0.5 value, presence of inhibitor of apoptosis domain BIR3, 37°C, pH 7.8
-
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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
0.029
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
0.029
Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide)
protease 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
0.00067
beta-casein
mutant enzyme F131A, in the presence of activator peptide BIR2, pH and temperature not specified in the publication
-
0.0011
beta-casein
wild type enzyme, in the absence of activator peptide BIR2, pH and temperature not specified in the publication
-
0.0018
beta-casein
mutant enzyme P148A, in the absence of activator peptide BIR2, pH and temperature not specified in the publication
-
0.003
beta-casein
wild type enzyme, in the presence of activator peptide BIR2, pH and temperature not specified in the publication
-
0.0039
beta-casein
mutant comprising N-terminal and serine protease domains, pH 8.0, 37°C
-
0.0051
beta-casein
mutant enzyme P148A, in the presence of activator peptide BIR2, pH and temperature not specified in the publication
-
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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
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
0.0002
beta-casein
mutant enzyme F131A, in the presence of activator peptide BIR2, pH and temperature not specified in the publication
-
0.26
beta-casein
mutant G230A, presence of inhibitor of apoptosis domain BIR3, 37°C, pH 7.8
-
0.27
beta-casein
wild type enzyme, in the presence of activator peptide BIR2, pH and temperature not specified in the publication
-
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
-
1.03
beta-casein
mutant enzyme P148A, in the absence of activator peptide BIR2, pH and temperature not specified in the publication
-
1.12
beta-casein
wild type enzyme, in the absence of activator peptide BIR2, pH and temperature not specified in the publication
-
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
-
3.73
beta-casein
mutant enzyme P148A, in the presence of activator peptide BIR2, pH and temperature not specified in the publication
-
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
-
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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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
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
45
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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
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
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
brenda
-
-
-
brenda
-
-
-
brenda
-
731129, 731620, 731798, 732357, 732718, 732929, 752820, 753038, 753188, 753695, 754456, 754775, 755128, 768982, 769060, 769117
SwissProt
brenda
-
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
platelets contain the pro-apoptotic proteins Omi/HtrA2 and Smac/Diablo, as well as their target, the X-linked inhibitor of apoptosis XIAP
brenda
-
human lung epithelial adenocarcinoma cell A549
brenda
-
benign tumor, borderline tumor, cancer, Krukenberg tumor
brenda
-
stem sections and cortical slices from patients with pathologically confirmed idiopathic Parkinson's disease
brenda
cerebral plaques in the brains of patients with Alzheimer´s disease
brenda
increased interaction between HtrA2 and vimentin in human primary neurons upon stress stimuli
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
halo of Lewy bodies from patients with pathologically confirmed idiopathic Parkinson's disease
-
brenda
-
HtrA2 released from the mitochondrion to the cytoplasm during apoptosis in response to oxidative stress
brenda
released into the cytosol upon apoptotic stimuli
brenda
released into the cytosol during apoptosis
brenda
N-truncated form is released into the cytosol upon apoptotic stimuli
brenda
-
Omi/HtrA2 relocates from mitochondria to the cytosol in lung adenocarcinoma cell line A549 under serum withdrawal
brenda
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
brenda
-
myocardial ischemia/reperfusion results in Omi/HtrA2 translocation from the mitochondria to the cytosol along with cytochrome c
brenda
-
H2O2-induced oxidative damage of retinal pigment epithelial cells results in HtrA2/Omi translocation from mitochondria to cytosol, leading to RPE cell apoptosis via a caspase-mediated pathway
brenda
-
focal cerebral ischemia in rats results in Omi/HtrA2 translocation from the mitochondria to the cytosol
brenda
-
mature protein is released form the mitochondria into the cytosol during aopotosis
brenda
-
extramitochondrially expressed enzyme induces atypical cell death
brenda
-
mitochondria also contain processed Omi which, following apoptotic insult, translocates to the cytosol
brenda
-
predominant localisation, enlarged mitochondria with disorganized cristae in mutant cells
brenda
-
normally expression of HtrA2, enzyme does not leave the mitochondria upon the TNF-alpha + zVAD-induced cell death in neutrophils
brenda
-
amyloid precursor protein is partly colocalized with HtrA2 in the mitochondria
brenda
-
intermembrane space, HtrA2/Omi is required for mitochondrial homeostasis
brenda
-
immunostaining and confocal microscopy shows that Omi/HtrA2 is located primarily in the mitochondria of lung adenocarcinoma cell line A549
brenda
-
S-nitrosoglutathione treatment induces redistribution of Omi/HtrA2 from cytoplasm to mitochondria in endothelial cells
brenda
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
brenda
-
in response to UV irradiation the enzyme shifts into the cytosol
brenda
-
HtrA2 in the intermembrane space of healthy cells, density of mitochondria decreased and showed abnormal forms in knockout mice
brenda
-
intermembrane space, HtrA2/Omi is required for mitochondrial homeostasis
brenda
-
following apoptotic stimuli, HtrA2 accumulates in the nucleus
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
-
the enzyme cleaves vimentin and affects vimentin assembly and polymerization following irradiation
physiological function
malfunction
-
in mouse embryonic HtrA2/omi knockout fibroblast cells the apoptosis-dependent cleavage of Wilms'tumor suppressor protein WT1 is prevented and expression of WT1 is upregulated
malfunction
-
endogenous levels of Parkin are significantly decreased in wild-type (HtrA2+/+) mouse embryonic fibroblasts compared with those in HtrA2-knockout (HtrA2-/-) mouse embryonic fibroblasts under the same stress conditions
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
-
in Omi/HtrA2 silenced Drosophila S2R+ cells 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
-
in Omi/HtrA2 knockout mouse embryonic fibroblasts 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. Complementation of knockout cells with human wild-type Omi/HtrA2 reverses the mitochondrial elongation phenotype and optic atrophy protein 1 alterations
malfunction
-
fewer and abnormal mitochondria are found in HtrA2/Omi knockout mice photoreceptors and pigment epithelial cells
malfunction
-
knockdown of Omi decreases the basal level of autophagy and increases the level of neurodegenerative proteins such as pathogenic A53T alpha-synuclein and truncated polyglutamine-expanded huntingtin, as well as the endogenous autophagy substrate p62
malfunction
-
Omi/HtrA2 knockout mice show significant increase in intramitochondrial reactive oxygen species and decreased mitochondrial membrane potential in MEF cells
malfunction
-
loss of mitochondrial Omi/HtrA2 is associated with S-nitrosoglutathione-induced apoptosis in human endothelial cells
malfunction
-
knockdown of HtrA2/Omi affords protection against interleukin-3 withdrawal-induced death in the presence of carbobenzoxy-valyl-analylaspartyl-[O-methyl]-fluoromethylketone
malfunction
-
enzyme inactivation leads to the growth retardation of adipocytes, thereby delaying the hair cycle of mnd2 mice
malfunction
-
decreased enzyme function damages mitochondrial quality in the heterozygous mouse brain cortex, leading to more brain ischemia/reperfusion injury. HtrA2-heterozygous mice show decreased mitochondrial quality control and reduced mitochondrial function after ischemia/reperfusion injury, decreased anti-damage ability and increased apoptosis after middle cerebral artery occlusion
malfunction
transient enzyme knock-down inhibits parasite growth, disrupts the intra-erythrocytic parasite cycle, and affects mitochondria development
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
-
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
-
Omi/HtrA2 interacts with thanatos-associated protein 5 in mammalian cells during apoptosis
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
-
Omi/HtrA2 is released from mitochondria to the cytosol and is required for annexin A2 cleavage under apoptotic stimuli
physiological function
-
Omi activates autophagy in a dose-dependent manner through digestion of Hax-1, Omi-induced autophagy facilitates the degradation of neurodegenerative proteins such as pathogenic A53T alpha-synuclein and truncated polyglutamine-expanded huntingtin, as well as the endogenous autophagy substrate p62. Omi is important in the cellular quality control of proteins involved in neurodegenerative diseases
physiological function
-
Omi/HtrA2 functionally and physically interacts with the mitochondrial fusion protein OPA1. Mitochondrial morphology relies on Omi/HtrA2 protease function
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
-
cytosolic HtrA2 decreases ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) protein level and its hydrolase activity through HtrA2-mediated cleavage of UCH-L1 under apoptotic conditions. HtrA2-mediated cleavage of UCH-L1 plays important roles in regulating the fine balance between cell growth and cell death
physiological function
-
HtrA2/Omi plays a role in caspase-independent cell death during growth factor withdrawal by cleaving receptor-interacting protein 1
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
pharmacological inhibition or genetic deletion of enzyme HtrA2/Omi protects from TNF-induced necroptosis. HtrA2/Omi does not cleave ubiquitin C-terminal hydrolase UCH-L1 during TNF-induced necroptosis, but rather induces monoubiquitination indicative for UCH-L1 activation. Correspondingly, pharmacologic or RNA interference-mediated inhibition of UCH-L1 protects from TNF-induced necroptosis
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
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
protease HtrA2 restricts the activation of apoptosis-associated speck-like protein containing a caspase-recruitment domain, i.e. ASC, dependent NLRP3 and AIM2 inflammasomes, in a protease activity-dependent manner. Disruption of the protease activity of HtrA2 results in exacerbated NLRP3 and AIM2 inflammasome responses in macrophages ex vivo and systemically in vivo. HtrA2 protease activity regulates autophagy and controls the magnitude and duration of inflammasome signaling by preventing prolonged accumulation of the inflammasome adaptor ASC
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
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
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 enzyme is involved in the cytoskeletal reorganization that accompanies radiation-induced senescence and the continuous maintenance of proliferation arrest
physiological function
-
the enzyme plays an essential role in regulating the adipogenesis-associated hair cycle
physiological function
the enzyme plays a crucial role in apoptosis by cleaving inhibitory and anti-apoptotic proteins by translocating from mitochondria to the cytosol
physiological function
the enzyme plays a dual role in maintenance of parasite mitochondria under normal conditions, as well as regulation of programmed cell death under cellular stress conditions. The enzyme activity is not essential for parasite survival
Show AA Sequence and Transmembrane Helices (1117 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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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
33000
dOmi-S, determined by SDS-PAGE and Western Blot analysis
35000
36000
37000
37900
x * 47620, calculated, immature protein, x * 37900, calculated, mature protein, x * 37000, SDS-PAGE of mature protein
38000
47620
x * 47620, calculated, immature protein, x * 37900, calculated, mature protein, x * 37000, SDS-PAGE of mature protein
50000
61790
-
GST-HtrA2, calculated by the Compute pI/Mw method at the ExPASy proteomics server of the Swiss Institute of Bioinformatics
63000
35000
dOmi-L, determined by SDS-PAGE and Western Blot analysis
37000
x * 47620, calculated, immature protein, x * 37900, calculated, mature protein, x * 37000, SDS-PAGE of mature protein
38000
unprocessed dOmi, determined by SDS-PAGE and Western Blot analysis
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
trimer
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
?
x * 47620, calculated, immature protein, x * 37900, calculated, mature protein, x * 37000, SDS-PAGE of mature protein
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
proteolytic modification
proteolytic modification
-
133 N-terminal amino acids of the precursor protein are cleaved off
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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
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
G363S
Drosophila Omi mutant analogous to human Omi/HtrA2 mutation G399S
HtrA2DELTA1
deletion mutant, the P-element G4907 is excised to produce a deletion of 1037 bp
S236C
Drosophila Omi mutant analogous to human Omi/HtrA2 mutation S276C
S266A
Drosophila Omi mutant analogous to human Omi/HtrA2 mutation S306A
S364A
Drosophila Omi mutant analogous to human Omi/HtrA2 mutation S400A
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
F131A
the mutant shows strongly decreased catalytyic efficiency in the presence of activator peptide BIR2 compared to the wild type enzyme
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
P148A
the mutant shows strongly increased catalytyic efficiency in the presence of activator peptide BIR2 compared to the wild type enzyme
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
S306A
HtrA2DELTA134-349
-
mutant, deletion of protease domain, no interaction with Hax1
HtrA2DELTAMTS
-
mutant, deletion of MTS domain, weaker interaction with Hax1 detected
HtrA2DELTAMTS-PDZ
-
mutant, deletion of MTS and PDZ domain, weaker interaction with Hax1 detected
HtrA2DELTAPDZ
-
mutant, deletion of PDZ domain, strong interaction with Hax1 detected
S276C
S306A
Y361A
-
mature Omi with PDZ domain mutation, cannot interact with C-terminus of WTS, fails to cleave full-length WTS
additional information
A141S
-
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
G399S
-
affects the enzymatic activity of the protease, associated with the development of Parkinsons disease
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
S276C
loss of protease activity, maturation and IAP-binding activity are not affected
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
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
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
additional information
-
HtrA2 knockout mice with general decrease in organ size and neurological abnormalities, deletion of HtrA2 results in a mitochondrial dysfunction, death of these mice ca. 30 days after birth
additional information
-
HtrA2 knockout MEFs, no endogenous PINK1. Show decreased mitochondrial membrane potential
additional information
-
mutations in the genes encoding HtrA proteins correlate with perinatal lethality in mice
additional information
mature protein can be stably expressed as thioredoxin fusion protein
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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
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
enzyme undergoes autoproteolysis
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-NTA column chromatography
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
-
rapid purification of GST-HtrA2/Omi fusion proteins under non-denaturing conditions by selective binding to glutathione-Sepharose 4B beads
-
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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
-
constructs encoding C-terminal His6-tagged full-length dOmi or truncated mutants are generated using the pET-21a and the pVL-1393 transfer vector, proteins are overexpressed in Escherichia coli BL21DE3 and Sf9 insect cells, respectively
expressed in Escherichia coli (BL21) transformed with pRSET containing cDNA for full-length wild-type Omi or mutant
-
expressed in Escherichia coli BL21(DE3) cells
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
-
into plasmid pEGFPN3 and plasmid pGEX-4T1-FLAG. Expression of GST-HtrA2 fusion protein in BL21 cells and in HEK-293 cells
-
into the pCR-Blunt vector and subsequently into the pAxCAwt cosmid for transfection
-
overexpression in Escherichia coli BL21 (DE3) and expressed in Saccharomyces cerevisiae EGY48/pLexA-hPag and their mutants
-
overexpression of Nma11p in Saccharomyces cerevisiae strain BYa by insertion of a C-terminal GFP-tag to the BIR1ORF
-
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
-
successful expression of full-length HtrA2/Omi as a GST fusion protein in Escherichia coli BL21 as compared to human HtrA2/Omi
-
ubiquitin carboxyl-terminal hydrolase L1 and HtrA2 are expressed as GST-fusion proteins in Escherichia coli
-
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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
-
after specific HtrA2 downregulation using RNAi, increased cell viability is measured in H2O2-treated ARPE-19 cells
-
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
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
additional information
medicine
-
way to limit renal injury by specifically inhibiting its proteolytic activity
medicine
-
way to limit renal injury by specifically inhibiting its proteolytic activity
medicine
-
myocardial ischemia/reperfusion significantly increases cytosolic Omi/HtrA2 content and markedly increases apoptosis, ucf-101 can inhibit apoptosis
medicine
-
transfecting cells with siRNA molecules against Omi effectively eliminate Omi/HtrA2 protein expression
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
-
HtrA2 knockout mice display features characteristic of a Parkinson syndrome, deletion of HtrA2 results in increased susceptibility to cell death stimuli, Smac/DIABOLO can compensate for the removal of HtrA2 in terms of neutralizing inhibitor of apoptosis proteins
medicine
amyloid beta, a pivotal factor implicated in the pathogenesis of Alzheimer´s disease interacts with HtrA2/Omi
medicine
-
Omi/HtrA2 is involved in neuronal cell death following focal cerebral ischemia/reperfusion. Blocking the proteolytic activity of Omi/HtrA2 with specific inhibitors, such as the ucf-101, may be a way to afford neuroprotection and minimize cellular damage in cerebral ischemia/reperfusion
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
-
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
-
link between HtrA2/Omi and Parkinsons disease or Alzheimers disease
medicine
-
the function of Omi/HtrA2 is linked to selective vulnerability of striatal neurons in Huntingtons disease
medicine
mutations of the OMI/HTRA2 gene are linked to Parkinsons disease
medicine
mutations in the OMI/HTRA2 gene are linked to Parkinsons disease
medicine
-
the study does not support a role of HtrA2 variants in the pathogenesis of Parkinsons disease
medicine
-
the function of Omi/HtrA2 is linked to selective vulnerability of striatal neurons in Huntingtons 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
-
therapeutic interventions that inhibit HtrA2 expression, translocation, or protease activity may provide attractive therapeutics in the treatment of cardiovascular diseases
medicine
loss of HtrA2 function might contribute to the activation of a stress response of mitochondrial origin in the brain that promotes neurodegeneration
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
-
HtrA2 is linked to cancer and neurodegeneration, like Alzheimers disease, Parkinsons disease, Huntingtons disease, and brain, kidney and myocardial ischemia, reperfusion
medicine
-
therapeutic interventions that inhibit HtrA2/Omi expression, translocation, or protease activity may represent novel therapeutic strategies for retinal pigment epithelial cells and retinal pigment epithelial cells-related 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
medicine
-
way to limit renal injury by specifically inhibiting its proteolytic activity
-
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
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
additional information
-
simple and rapid strategy for molecular cloning using a gel-free and antibiotic selection method, which allows for the complete elimination of DNA extraction by gel electrophoresis, and thus has several advantages over gel-based cloning methods, including a cloning efficiency that is approximately 10times higher due to the prevention of ethidium bromide ultraviolet-induced DNA damage and contamination with ligase inhibitors, the amount of plasmid DNA required is approximately five times less, and cloning time is several hours less
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
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