Information on EC 3.4.21.108 - HtrA2 peptidase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY hide
3.4.21.108
-
RECOMMENDED NAME
GeneOntology No.
HtrA2 peptidase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
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
show the reaction diagram
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
cleavage of C-N-linkage
hydrolysis of peptide bond
CAS REGISTRY NUMBER
COMMENTARY hide
204655-80-1
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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-
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
fragment; male Syrian hamster
UniProt
Manually annotated by BRENDA team
-
-
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Manually annotated by BRENDA team
C57BL6
-
-
Manually annotated by BRENDA team
no activity in Caenorhabditis elegans
-
-
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Manually annotated by BRENDA team
no activity in Mycoplasma genitalium
-
-
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Manually annotated by BRENDA team
no activity in Mycoplasma pneumoniae
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Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
strain BYa
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-
Manually annotated by BRENDA team
strain BYa
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Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(35S) Met-labeled proteolytically inactive S306 form of full length HtrA2 + H2O
?
show the reaction diagram
-
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-IRRVSYSF(Dnp)KK + H2O
?
show the reaction diagram
-
best substrate
-
?
(7-methoxycoumarin-4-yl)acetyl-VTLCAVPS(Dnp)KK + H2O
?
show the reaction diagram
-
cleavage occurs between cysteine and alanine
-
?
(7-methoxycoumarin-4-yl)AIRRVSYSF-(5-amino-2-nitro)benzamide + H2O
?
show the reaction diagram
-
-
-
-
?
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
show the reaction diagram
-
-
-
-
?
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
show the reaction diagram
-
-
-
-
?
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
show the reaction diagram
-
-
-
-
?
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
show the reaction diagram
-
-
-
-
?
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
show the reaction diagram
-
-
-
-
?
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
show the reaction diagram
-
-
-
-
?
35S-beta-casein + H2O
?
show the reaction diagram
-
C-terminus of presenilin-1 interacts the PDZ domain of with Omi/HtrA2, increasing its activity
-
-
?
A beta 40
?
show the reaction diagram
-
HtrA2/Omi binds preferentially to the short form of A beta peptides, the enzyme does not perform degradation by direct hydrolysis
-
-
?
A beta 42
?
show the reaction diagram
-
HtrA2/Omi binds poorly to A beta 42, the enzyme does not perform degradation by direct hydrolysis
-
-
?
alpha-casein + H2O
?
show the reaction diagram
alpha-secretase peptide
?
show the reaction diagram
-
HtrA2/Omi does not perform degradation by direct hydrolysis
-
-
?
amyloid precursor protein + H2O
?
show the reaction diagram
amyloid precursor protein-like protein 1 + H2O
?
show the reaction diagram
-
processed into two major fragments of 65 and 67 kDa
-
-
?
amyloid precursor protein-like protein 2 + H2O
?
show the reaction diagram
-
processed into cleaved fragments of 103 and 109 kDa
-
-
?
Apollon + H2O
?
show the reaction diagram
beta-casein
?
show the reaction diagram
-
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-casein + H2O
?
show the reaction diagram
beta-secretase peptide
?
show the reaction diagram
-
HtrA2/Omi does not perform degradation by direct hydrolysis
-
-
?
Bir1p
?
show the reaction diagram
Bir1p + H2O
?
show the reaction diagram
c-inhibitor of apoptosis protein1 + H2O
?
show the reaction diagram
-
C-terminus of presenilin-1 interacts with the PDZ domain of Omi/HtrA2, increasing its activity
-
-
?
c-inhibitor of apoptosis protein2 + H2O
?
show the reaction diagram
-
C-terminus of presenilin-1 interacts with the PDZ domain of Omi/HtrA2, increasing its activity
-
-
?
casein + H2O
?
show the reaction diagram
dephosphorylated casein + H2O
?
show the reaction diagram
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-
-
?
Fas-Fas L + H2O
?
show the reaction diagram
-
-
-
-
?
FLIP + H2O
?
show the reaction diagram
-
Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein
-
-
?
gamma-secretase peptide
?
show the reaction diagram
-
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
-
-
?
glycoprotein alpha1 + H2O
?
show the reaction diagram
-
-
-
-
?
glycprotein alpha1 acid + H2O
?
show the reaction diagram
-
-
-
?
HS1-associated protein X-1 + H2O
?
show the reaction diagram
-
HtrA2/Omi-mediated degradation of HS1-associated protein X-1 correlates with extensive cell death in response to etoposide, cisplatin and H2O2
-
-
?
HS1-associated protein X1 + H2O
?
show the reaction diagram
-
HAX-1
-
-
?
hyaluronidase + H2O
?
show the reaction diagram
inhibitor of apoptosis + H2O
?
show the reaction diagram
Livin alpha + H2O
?
show the reaction diagram
-
-
-
?
Livin beta
?
show the reaction diagram
-
-
-
?
parkin + H2O
?
show the reaction diagram
PDZ-interacting peptides + H2O
?
show the reaction diagram
-
-
-
-
?
PED-PEA 15 + H2O
?
show the reaction diagram
-
death effector domain-containing protein
-
-
?
ped/pea-15
?
show the reaction diagram
-
HtrA2 is a specific interactor of the ped/pea-15 death effector domain and leads to its degradation
-
-
?
protein cIAP1 + H2O
?
show the reaction diagram
-
best substrate, preferred cleavage sites are after Thr4, Asn133 and Leu161
-
?
protein cIAP2 + H2O
?
show the reaction diagram
-
-
-
?
protein DIAP1 + H2O
?
show the reaction diagram
-
-
-
?
protein XIAP + H2O
?
show the reaction diagram
-
-
-
?
receptor-interacting protein 1 + H2O
?
show the reaction diagram
-
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
-
-
?
reduced bovine serum albumin
?
show the reaction diagram
-
HtrA2-Opt peptides stimulate the delta N-HtrA1 protease activity more than 3fold
-
-
?
SPMFKGV-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
tau protein + H2O
?
show the reaction diagram
-
enzyme degrades aggregated and fibrillar tau, a protein critically involved in various neurological disorders
-
-
?
thanatos-associated protein 5 (THAP5) + H2O
?
show the reaction diagram
-
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
-
-
?
ubiquitin carboxyl-terminal hydrolase L1 + H2O
?
show the reaction diagram
-
natural substrate for HtrA2 in the apoptotic pathway. HtrA2 directly cleaves UCH-L1 and inhibits its hydrolase activity
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-
?
unidentified substrate + H2O
?
show the reaction diagram
-
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
?
show the reaction diagram
-
WARTS, WTS, large tumor-suppressor 1 mitotic kinase
-
-
?
Wilms' tumor suppressor 1 + H2O
?
show the reaction diagram
Wilms' tumor suppressor protein WT1 + H2O
?
show the reaction diagram
WTS + H2O
?
show the reaction diagram
X-linked inhibitor of apoptosis protein
?
show the reaction diagram
-
HtrA2 promotes degradation of the X-linked inhibitor of apoptosis protein followed by subsequent caspase activation
-
-
?
X-linked inhibitor of apoptosis protein + H2O
?
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
amyloid precursor protein + H2O
?
show the reaction diagram
-
-
-
-
?
Bir1p
?
show the reaction diagram
parkin + H2O
?
show the reaction diagram
thanatos-associated protein 5 (THAP5) + H2O
?
show the reaction diagram
-
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
-
-
?
ubiquitin carboxyl-terminal hydrolase L1 + H2O
?
show the reaction diagram
-
natural substrate for HtrA2 in the apoptotic pathway. HtrA2 directly cleaves UCH-L1 and inhibits its hydrolase activity
-
-
?
Wilms' tumor suppressor 1 + H2O
?
show the reaction diagram
Wilms' tumor suppressor protein WT1 + H2O
?
show the reaction diagram
additional information
?
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5-[5-(2-nitrophenyl)furfuryliodine]1,3-diphenyl-2-thiobarbituric acid
-
UCF-101
antisense HtrA2
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significantly inhibits IFN/all-trans retinoic acid-induced degradation of X-linked inhibitor of apoptosis protein
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diisopropylfluorophosphate
-
complete inhibition at 4 mM
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
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ratio of C161M/APP decreases 66% during 0.0040 mM etoposide-induced apoptosis compared with the non-apoptotic condition
HtrA2 siRNA
-
-
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N-tosyllysine chloromethyl ketone
Omi siRNA
-
-
-
phenylmethanesulfonyl fluoride
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51% inhibition at 5 mM
siRNA
-
staurosporine
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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
TLCK
-
-
ucf-101
-
ucf-102
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inhibits, but to a lesser extent than ucf-101
-
ucf-103
-
inhibits, but to a lesser extent than ucf-101
-
ucf-104
-
58% inhibition at 0.02 mM
-
UCF101
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viral mitochondrial inhibitor of apoptosis
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vMIA
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vIRF1
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human herpes virus-8 (HHV-8)-coded oncoprotein, disrupts interactions of GRIM-19 with HtrA2
-
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
casein
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2.5fold activation
cisplatin
DKVLVVWAGQQ
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full-length denatured alpha-amylase, as well as alpha-amylase fragments and the C-terminus of alpha-amylase, amplify DegP proteolysis
DNRNGNVYDF
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-
DNRNGNVYFF
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2.5fold activation
DNRNGNVYGF
-
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DNRNGNVYIF
-
-
DNRNGNVYKF
-
-
DNRNGNVYLF
-
-
DNRNGNVYQF
-
1.5fold activation
DNRNGNVYSF
-
-
DNRNGNVYWF
-
2fold activation
DNRNGNVYYF
-
-
GRIM-19
-
direct enhancement of HtrA2 activity in vitro. HtrA2-driven destruction of the antiapoptotic X-linked inhibitor of apoptosis protein is augmented
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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
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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
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IVALGLVYQF
-
outer membrane porin C, 3fold activation
L-phenylalanine
-
essential for the formation of a homotrimer and for the HtrA2 serine protease activity
Mpv17l
-
PDZ domain G230A
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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
-
staurosporine
tunicamycin
-
-
WTS
-
activator of Omi protease
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X-linked inhibitor of apoptosis protein
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i.e. XIAP, binding of XIAP to the Reaper motif of the enzyme results in a marked increase in proteolytic activity
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YTMKAAGLGK
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alkaline phosphatase A
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
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
0.0014 - 0.00932
beta-casein
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.05
(7-methoxycoumarin-4-yl)AIRRVSYSF-(5-amino-2-nitro)benzamide
Homo sapiens
-
pH 8.0, 45°C
0.22
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-His-Tyr(3-NO2)-NH2
Homo sapiens
-
pH 8.0, 37°C
0.33
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
Homo sapiens
-
pH 8.0, 37°C
0.17
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2
Homo sapiens
-
pH 8.0, 37°C
0.01
2-aminobenzoic acid-Ile-Met-Thr-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
Homo sapiens
-
pH 8.0, 37°C
0.13
2-aminobenzoic acid-Ile-Met-Val-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
Homo sapiens
-
pH 8.0, 37°C
0.08
2-aminobenzoic acid-Ile-Met-Val-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
Homo sapiens
-
pH 8.0, 37°C
0.000025 - 0.0204
beta-casein
-
0.56
SPMFKGV-para-nitroaniline
Bacteria
-
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
31.13
(7-methoxycoumarin-4-yl)AIRRVSYSF-(5-amino-2-nitro)benzamide
Homo sapiens
-
pH 8.0, 45°C
202303
5.623
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-His-Tyr(3-NO2)-NH2
Homo sapiens
-
pH 8.0, 37°C
202299
14.53
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
Homo sapiens
-
pH 8.0, 37°C
202297
1.588
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2
Homo sapiens
-
pH 8.0, 37°C
202298
0.028
2-aminobenzoic acid-Ile-Met-Thr-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
Homo sapiens
-
pH 8.0, 37°C
202300
4.17
2-aminobenzoic acid-Ile-Met-Val-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
Homo sapiens
-
pH 8.0, 37°C
202302
0.681
2-aminobenzoic acid-Ile-Met-Val-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
Homo sapiens
-
pH 8.0, 37°C
202301
0.0026 - 4.7
beta-casein
3870
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.33
DPMFKL
Homo sapiens
-
protease HtrA2 mutant lacking the regulatory domain, pH 8.0, 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
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 hide
LITERATURE
7.4
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20
-
activity is practically negligible at 20 °C
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
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.7
-
calculated from nucleotide sequence
9.4
calculated
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
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
Manually annotated by BRENDA team
-
human lung epithelial adenocarcinoma cell A549
Manually annotated by BRENDA team
-
from the peripheral blood of healthy donors
Manually annotated by BRENDA team
-
benign tumor, borderline tumor, cancer, Krukenberg tumor
Manually annotated by BRENDA team
additional information
-
proximal cells, HK-2 cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
-
halo of Lewy bodies from patients with pathologically confirmed idiopathic Parkinson's disease
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
37400
-
mature HtrA2, determined by SDS-PAGE and Western blot analysis
37900
x * 47620, calculated, immature protein, x * 37900, calculated, mature protein, x * 37000, SDS-PAGE of mature protein
39000
-
mature HtrA2 protein
40000
-
determined by SDS-PAGE and Western Blot analysis
42000
-
SDS-PAGE
46000
-
full-length protein
47620
x * 47620, calculated, immature protein, x * 37900, calculated, mature protein, x * 37000, SDS-PAGE of mature protein
48840
-
-
49000
-
pro-HtrA2, determined by SDS-PAGE and Western Blot analysis
49500
-
HtrA2 precursor, determined by SDS-PAGE and Western blot analysis
60000
-
by immunoblotting
61790
-
GST-HtrA2, calculated by the Compute pI/Mw method at the ExPASy proteomics server of the Swiss Institute of Bioinformatics
77000
-
-
110000
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 47620, calculated, immature protein, x * 37900, calculated, mature protein, x * 37000, SDS-PAGE of mature protein
homotrimer
-
-
trimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
proteolytic modification
ubiquitination
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Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
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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
enzyme undergoes autoproteolysis
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C
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-70°C, Tris-HCl buffer, 20% glycerol, several months
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-70°C, Tris-HCl buffer, pH 7.6, 20% glycerol, several months
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-80°C, HEPES-KOH buffer, pH 7.5
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-80°C, phosphate buffered saline, pH 7.4, 20% glycerol
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
90% pure
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affinity purified
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by gel filtration
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by glutathione-Sepharose 4B beads
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by glutathione-Sepharose beads
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by nickel affinity chromatography and HiTrap desalting
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glutathione 4B bead chromatography
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GST fusions purified by selective binding to glutathione-Sepharose 4B beads
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immunopurified from HEK-293 T cells
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mitochondrial and cytosolic fractions are prepared
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mitochondrial fractions of HEK-293T cells are prepared
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on Ni-NTA agarose column
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on Ni2+ agarose beads
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rapid purification of full-length HtrA2/Omi as a GST fusion under non-denaturing conditions by selective binding to glutathione-Sepharose 4B beads
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rapid purification of GST-HtrA2 delta 133 proteins on glutathione-Sepharose 4B beads
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rapid purification of GST-HtrA2/Omi fusion proteins under non-denaturing conditions by selective binding to glutathione-Sepharose 4B beads
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recombinant enzyme by ProBondTM resin
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sequential S-100 and S-200 gel filtration chromatography
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using TALON agarose
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with Ni-NTA-agarose column
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
barely expressed full-length HtrA2/Omi as a GST fusion protein in Escherichia coli BL21
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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
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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
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expressed in Escherichia coli (BL21) transformed with pRSET containing cDNA for full-length wild-type Omi or mutant
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expressed in human embryonic kindney cells and in Escherichia coli
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expressed in yeast as a bait protein in a two-hybrid assay and by transient transfection of Human embryonic kidney (HEK)-293 cells
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expression as GST fusions in Escherichia coli BL21
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expression from pET-15b
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expression in Escherichia coli
expression in Escherichia coli and MEF cells from mnd2 mouse
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expression in Escherichia coli BL21 (DE3)
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expression in Escherichia coli BL21 (DE3) pLysS
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expression in Escherichia coli BL21 Codon Plus (DE3)-RIL
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expression of GST-HtrA2 delta 133 proteins in Escherichia coli BL21 from GST-HTRA2 delta 133 WT, S306 and F149D constructs
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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
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into pDNA3.1+
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into plasmid pEGFPN3 and plasmid pGEX-4T1-FLAG. Expression of GST-HtrA2 fusion protein in BL21 cells and in HEK-293 cells
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into the pCR-Blunt vector and subsequently into the pAxCAwt cosmid for transfection
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into the vector pCMV/SPORT
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into the vectors pCaSpeR-HS and pUASp
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into the vectors pUASt and pTMR
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overexpression in Escherichia coli BL21 (DE3) and expressed in Saccharomyces cerevisiae EGY48/pLexA-hPag and their mutants
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overexpression in HeLa cells and HEK-293 cells
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overexpression of Nma11p in Saccharomyces cerevisiae strain BYa by insertion of a C-terminal GFP-tag to the BIR1ORF
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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
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PDZ domain
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recombinantly expressed
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subcloned into pET28a and propageted in Escherichia coli DH5alpha, expressed in Escherichia coli BL21 (DE3) pLys, overexpression in K269 cells
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successful expression of full-length HtrA2/Omi as a GST fusion protein in Escherichia coli BL21 as compared to human HtrA2/Omi
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TAP-tagged HtrA2 stably expressed in HEK-293 cells
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truncated version, expressed in Escherichia coli
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ubiquitin carboxyl-terminal hydrolase L1 and HtrA2 are expressed as GST-fusion proteins in Escherichia coli
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yes into the ecdysone-inducible eukaryotic expression vector pIND
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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
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ablation of HtrA2 activity using RNAi in the human osteosarcoma U2OS cells prevents the cleavage of Wilms'tumor suppressor protein WT1 under apoptotic conditions
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after specific HtrA2 downregulation using RNAi, increased cell viability is measured in H2O2-treated ARPE-19 cells
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isoform HTRA1 mRNA and HTRA1 activity are up-regulated in response to elevated tau concentrations
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Omi/HtrA2 siRNA decreases the cleavage of annexin A2 lung epithelial adenocarcinoma cell A549 under both serum withdrawal and cisplatin treatment
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S-nitrosoglutathione treatment significantly decreases mitochondrial Omi/HtrA2 content after 8 h of exposure in endothelial cells
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S-nitrosoglutathione treatment significantly increases cytosolic Omi/HtrA2 content after 8 h of exposure in endothelial cells
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the expression level of HtrA2/Omi decreases with endoplasmic reticulum stress induction in 6-hydroxydopamine-treated SH-SY5Y cells
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
R262A
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completely abolishes proteolytic activation
V328S
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completely abolishes proteolytic activation
G363S
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Drosophila Omi mutant analogous to human Omi/HtrA2 mutation G399S
HtrA2DELTA1
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deletion mutant, the P-element G4907 is excised to produce a deletion of 1037 bp
S236C
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Drosophila Omi mutant analogous to human Omi/HtrA2 mutation S276C
S266A
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Drosophila Omi mutant analogous to human Omi/HtrA2 mutation S306A
S306A
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mutant shows abolished protease activity
S364A
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Drosophila Omi mutant analogous to human Omi/HtrA2 mutation S400A
A227S
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HtrA2 variant
E292A
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residue involved in most of the peptide interactions, about 30% of wild-type catalytic efficiency
E296A
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residue involved in most of the peptide interactions, about 90% of wild-type catalytic efficiency
F16D
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residue involved in most of the peptide interactions, almost complete loss of catalytic activity
F172V
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HtrA2 variant
F303W
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mutation does not cause significant destabilizing or stabilizing effects on the thermal denaturation
F331W
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mutation in proease domain, mutation does not cause significant destabilizing or stabilizing effects on the thermal denaturation
F331Y
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inactive
G230A
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residue involved in most of the peptide interactions, about 12% of wild-type catalytic efficiency
I329N
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inactive
L118L
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HtrA2 variant
L286V
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Alzheimer mutant presenilin-1
L367L
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HtrA2 variant
L367W
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mutation does not cause significant destabilizing or stabilizing effects on the thermal denaturation
L377W
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mutation in PDZ domain, mutation does not cause significant destabilizing or stabilizing effects on the thermal denaturation
M146V
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Alzheimer mutant presenilin-1
N216A/S219A
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residues involved in most of the peptide interactions, about 33% of wild-type catalytic efficiency
P128L
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HtrA2 variant
R209R
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HtrA2 variant
R404W
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mutation within the PDZ domain, inactive protein
R432L
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mutation in PDZ domain, significant increase in activity
S142A
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considerably less phosphorylated by p38gamma in vitro. Markedly lower protease activity than its acidic counterpart
S212A
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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
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mutant mimicking phosphorylation. It has lost the protease activity and fails to induce programmed cell death
S276C
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deletion of the PDZ domain of Omi/HtrA2
S400A
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considerably less phosphorylated by p38gamma in vitro. Markedly lower protease activity than its acidic counterpart
V109V
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HtrA2 variant
V226K
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mutation in protease domain, significant increase in activity
V226K E429L
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salt link formation is no longer possible, the increase of activity observed for mutant V226K ceased to exist
V226W
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mutation in proease domain, proteolytic activity similar to wild-type
V325D
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inactive
V364W
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mutation does not cause significant destabilizing or stabilizing effects on the thermal denaturation
W12C
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HtrA2 variant
Y361W
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mutation in proease domain, proteolytic activity similar to wild-type
A144G
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mutation reduces ability to promote cell death, weak interaction with XIAP
A147I
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increased affinity for the BIR3 domain of XIAP
F149D
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comparable level of binding to XIAP as the wild type-enzyme
S306A/A144G
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complete loss of proapoptotic activity
HtrA2DELTA134-349
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mutant, deletion of protease domain, no interaction with Hax1
HtrA2DELTAMTS
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mutant, deletion of MTS domain, weaker interaction with Hax1 detected
HtrA2DELTAMTS-PDZ
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mutant, deletion of MTS and PDZ domain, weaker interaction with Hax1 detected
HtrA2DELTAPDZ
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mutant, deletion of PDZ domain, strong interaction with Hax1 detected
HtrA2S306A
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inactive mutant
HtrA2_350-458
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mutant, PDZ domain, no interaction with Hax1
Y361A
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mature Omi with PDZ domain mutation, cannot interact with C-terminus of WTS, fails to cleave full-length WTS
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
additional information
Show AA Sequence (534 entries)
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