3.4.21.108: HtrA2 peptidase
This is an abbreviated version!
For detailed information about HtrA2 peptidase, go to the full flat file.
Word Map on EC 3.4.21.108
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3.4.21.108
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xiap
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bcl-2
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parkinson
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proapoptotic
-
caspases
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caspase-independent
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aif
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x-linked
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medicine
-
apoptosis-inducing
-
intermembrane
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htras
-
pink1
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apoptogenic
-
iap-binding
-
apoptosome
- 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
cleavage of non-polar aliphatic amino-acids at the P1 position, with a preference for Val, Ile and Met. At the P2 and P3 positions, Arg is selected most strongly with a secondary preference for other hydrophilic residues =
Synonyms
DegP, dOmi/HtrA2, high temperature requirement A serine protease, high temperature requirement A2, high temperature requirement A2 protease, high temperature requirement A2 serine protease, high temperature requirement protein A2, high-temperature requirement factor A2, HtrA protease, HtrA/DegP, HtrA2, HtrA2 protease, HtrA2 serine protease, HtrA2(Omi), HtrA2/Omi, HtrA2/Omi serine protease, Nma11p, Omi, Omi protease, Omi/HtrA2, Omi/HtrA2 protease, Omi/HtrA2 serine protease, pro-apoptotic serine protease, S01.278, serine protease, serine protease HtrA2, serine protease HtrA2/Omi, serine protease Omi/HtrA2
ECTree
3.4.21.108 HtrA2 peptidaseAdvanced search results
results (
results (Substrates Products
Substrates Products on EC 3.4.21.108 - HtrA2 peptidase
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SUBSTRATE 
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(35S) Met-labeled proteolytically inactive S306 form of full length HtrA2 + H2O
?
-
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-IRRVSYSF(Dnp)KK + H2O
?
-
best substrate
-
?
(7-methoxycoumarin-4-yl)acetyl-VTLCAVPS(Dnp)KK + H2O
?
-
cleavage occurs between cysteine and alanine
-
?
(7-methoxycoumarin-4-yl)AIRRVSYSF-(5-amino-2-nitro)benzamide + H2O
?
-
-
-
?
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-His-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoic acid-Ile-Met-Thr + Abu-Tyr-Met-His-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoic acid-Ile-Met-Thr + Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoic acid-Ile-Met-Thr-Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoic acid-Ile-Met-Thr + Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoic acid-Ile-Met-Thr-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoic acid-Ile-Met-Thr + Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoic acid-Ile-Met-Val-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoic acid-Ile-Met-Val + Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoic acid-Ile-Met-Val-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoic acid-Ile-Met-Val + Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoyl-Ile-Met-Thr-Abu-Tyr-Met-His-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoyl-Ile-Met-Thr + Abu-Tyr-Met-His-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoyl-Ile-Met-Thr-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoyl-Ile-Met-Thr + Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoyl-Ile-Met-Thr-Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoyl-Ile-Met-Thr + Abu-Tyr-Met-Trp-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoyl-Ile-Met-Val-Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoyl-Ile-Met-Val + Abu-Tyr-Met-Phe-Tyr(3-NO2)-NH2
-
-
-
?
2-aminobenzoyl-Ile-Met-Val-Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2 + H2O
2-aminobenzoyl-Ile-Met-Val + Ser-Tyr-Met-Phe-Tyr(3-NO2)-NH2
-
-
-
?
35S-beta-casein + H2O
?
-
C-terminus of presenilin-1 interacts the PDZ domain of with Omi/HtrA2, increasing its activity
-
-
?
A beta 40
?
-
HtrA2/Omi binds preferentially to the short form of A beta peptides, the enzyme does not perform degradation by direct hydrolysis
-
-
?
A beta 42
?
-
HtrA2/Omi binds poorly to A beta 42, the enzyme does not perform degradation by direct hydrolysis
-
-
?
alpha-secretase peptide
?
-
HtrA2/Omi does not perform degradation by direct hydrolysis
-
-
?
amyloid precursor protein-like protein 1 + H2O
?
-
processed into two major fragments of 65 and 67 kDa
-
-
?
amyloid precursor protein-like protein 2 + H2O
?
-
processed into cleaved fragments of 103 and 109 kDa
-
-
?
beta-casein
?
-
protease activity is activated by the binding of the PDZ domain of the mature form of Omi to the C-terminal region of the reduced form of Pag
-
-
?
beta-secretase peptide
?
-
HtrA2/Omi does not perform degradation by direct hydrolysis
-
-
?
c-inhibitor of apoptosis protein1 + H2O
?
-
C-terminus of presenilin-1 interacts with the PDZ domain of Omi/HtrA2, increasing its activity
-
-
?
c-inhibitor of apoptosis protein2 + H2O
?
-
C-terminus of presenilin-1 interacts with the PDZ domain of Omi/HtrA2, increasing its activity
-
-
?
FLIP + H2O
?
-
Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein
-
-
?
gamma-secretase peptide
?
-
HtrA2/Omi binds less strongly to gamma-secretase substrate peptide as compared to alpha-secretase substrate peptide and beta-secretase substrate peptide, the enzyme does not perform degradation by direct hydrolysis
-
-
?
HS1-associated protein X-1 + H2O
?
-
HtrA2/Omi-mediated degradation of HS1-associated protein X-1 correlates with extensive cell death in response to etoposide, cisplatin and H2O2
-
-
?
ped/pea-15
?
-
HtrA2 is a specific interactor of the ped/pea-15 death effector domain and leads to its degradation
-
-
?
protein cIAP1 + H2O
?
-
best substrate, preferred cleavage sites are after Thr4, Asn133 and Leu161
-
?
receptor-interacting protein 1 + H2O
?
-
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
?
-
HtrA2-Opt peptides stimulate the delta N-HtrA1 protease activity more than 3fold
-
-
?
thanatos-associated protein 5 (THAP5) + H2O
?
-
in a yeast two-hybrid assay it is shown that Omi/HtrA2 protease interacts with thanatos-associated protein 5. Degradation assays show that thanatos-associated protein 5 is cleaved by Omi/HtrA2
-
-
?
ubiquitin carboxyl-terminal hydrolase L1 + H2O
?
-
natural substrate for HtrA2 in the apoptotic pathway. HtrA2 directly cleaves UCH-L1 and inhibits its hydrolase activity
-
-
?
unidentified substrate + H2O
?
-
its cleavage by Omi/HtrA2 leads to permeabilization of the mitochondria outer membrane and release of chytochrome c followed by enhanced caspase activation
-
-
?
WARTS kinase + H2O
?
-
WARTS, WTS, large tumor-suppressor 1 mitotic kinase
-
-
?
X-linked inhibitor of apoptosis protein
?
-
HtrA2 promotes degradation of the X-linked inhibitor of apoptosis protein followed by subsequent caspase activation
-
-
?
Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide) + H2O
?
-
-
-
?
Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitrobenzamide) + H2O
?
-
-
-
?
amyloid precursor protein + H2O
?
-
efficient cleavage by HtrA2 in the normal physiological condition. HtrA2-mediated cleavage product is the C161 fragment encompassing amino acids 535695 of amyloid precursor protein 695. Mature HtrA2 and full-length HtrA2 can process amyloid precursor protein into C161
-
-
?
Apollon + H2O
?
-
HtrA2 cleaves Apollon, a huge inhibitor of apoptosis protein, with its serine protease activity, conversely, Apollon ubiquitylates and facilitates proteasomal degradation of HtrA2, thus both downregulate each other
-
-
?
beta-casein + H2O
?
-
main selectivity at position P1 is for non-polar aliphatic amino acids, in particular valine, isoleucine and methionine. At the P2 and P3 positions arginine is selected most strongly with a secondary selection for other hydrophilic residues
-
?
beta-casein + H2O
?
-
cleaved to approximately 50% by GST-HtrA2 after a cleavage reaction for 1 h
-
-
?
Bir1p + H2O
?
-
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
-
-
?
Bir1p + H2O
?
-
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
-
-
?
parkin + H2O
?
-
using cleavage and binding assays, it is demonstrated that HtrA2 specifically binds to and directly cleaves the E3 ubiquitin ligase Parkin
-
-
?
Wilms' tumor suppressor 1 + H2O
?
-
bona fide substrate for HtrA2-mediated proteolysis, cleavage sites are in the C terminus at Val286 and Leu320, resulting in fragments of 20000 and 35000 Da, respectively, while another cleavage site is in the N terminus at Leu91 adjacent to suppression domain
-
-
?
Wilms' tumor suppressor 1 + H2O
?
-
HtrA2 cleaves at, at least, two specific sites. Wilms' tumor suppressor 1 degradation by HtrA2 reveals two major proteolytic products of 20000 Da and 15000 Da, but the same samples immunoblotted with N-Ter antibody reveals major fragment sizes of 35000 Da and 30000 Da. The potential cleavage site that produces the 20000 Da fragment is at Val286, and the potential cleavage site producing the 15000 Da fragment is at Leu320
-
-
?
Wilms' tumor suppressor protein WT1 + H2O
?
-
using a yeat two-hybrid assay WT1 is identified as a binding partner of HtrA2/Omi. HtrA2/Omi cleaves WT1 at multiple binding sites following the treatment of cells with cytotoxic drugs
-
-
?
X-linked inhibitor of apoptosis protein + H2O
?
-
-
-
-
?
X-linked inhibitor of apoptosis protein + H2O
?
-
autocatalytically processing of HtrA2 to the 36-kDa protein fragment, which is required for the cytochrome c-dependent caspase activation, promoting apoptotic cell death
-
-
?
X-linked inhibitor of apoptosis protein + H2O
?
-
C-terminus of presenilin-1 interacts with the PDZ domain of Omi/HtrA2, increasing its activity
-
-
?
X-linked inhibitor of apoptosis protein + H2O
?
-
homotrimeric structure of enzyme is required for executing its activity
-
-
?
X-linked inhibitor of apoptosis protein + H2O
?
-
Omi/HtrA2 cleaves as well as directly binds and inactivates X-linked inhibitor of apoptosis protein to promote caspase activation
-
-
?
additional information
?
-
-
no cleavage of STDGGV-para-nitroaniline and SKAKGGEEPLPEGV-para-nitroaniline
-
-
?
additional information
?
-
cleavage of DIAP1 between the BIR1 and BIR2 domain and further degradation of BIR1
-
-
?
additional information
?
-
-
Omi can degrade inhibitor of apoptosis proteins
-
?
additional information
?
-
-
can promote caspase activation and cell death apoptosis
-
?
additional information
?
-
-
induces atypical cell death. Inhibits the caspase-inhibitory activity of XIAP by direct binding to it. Only mature form but not its precursor binds to IAPs
-
?
additional information
?
-
-
role in apoptosis, amino-terminal IAP interaction motif displaces IAPs from caspases, leading to enhanced caspase activity
-
?
additional information
?
-
-
role in apoptosis, binds to XIAP-binding protein
-
?
additional information
?
-
role in apoptosis, degradation of aberrantly folded proteins during conditions of cellular stress
-
?
additional information
?
-
-
role in apoptosis, degradation of aberrantly folded proteins during conditions of cellular stress
-
?
additional information
?
-
-
role in apoptosis, enzyme can induce apoptosis in a caspase-independent manner through its protease activity and in a caspase-dependent manner via its ability to disrupt caspase-IAP interaction
-
?
additional information
?
-
-
does not bind the reversed control peptide A beta 41-1 and peptide H2-Opt
-
-
?
additional information
?
-
-
degradation of inhibitor of apoptosis proteins, IAPs
-
-
?
additional information
?
-
-
HtrA2 cleaves p73alpha in the C-terminal portion
-
-
?
additional information
?
-
-
co-immunoprecipitation show direct interaction of Omi/HtrA2 with optic atrophy protein 1 (OPA1)
-
-
?
additional information
?
-
-
HtrA2 fails to cleave the Wilms' tumor suppressor 1 cofactors Par-4 and BASP1
-
-
?
additional information
?
-
allostery does regulate HtrA2 activity using a non-canonical selective binding pocket in HtrA2 which initiates signal propagation to the distal active site through a complex allosteric mechanism
-
-
?
additional information
?
-
-
induces cell death in a caspase-dependent manner
-
?
additional information
?
-
-
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
-
?
additional information
?
-
loss of enzyme activity causes neuromuscular disorder
-
?
additional information
?
-
-
loss of enzyme activity causes neuromuscular disorder
-
?
additional information
?
-
-
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
-
?
