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
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caspases
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caspase-independent
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aif
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x-linked
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medicine
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apoptosis-inducing
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intermembrane
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htras
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pink1
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apoptogenic
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iap-binding
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apoptosome
- 3.4.21.108
- xiap
- bcl-2
- parkinson
-
proapoptotic
-
caspases
-
caspase-independent
- aif
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x-linked
- medicine
-
apoptosis-inducing
-
intermembrane
-
htras
- pink1
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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 (Engineering
Engineering on EC 3.4.21.108 - HtrA2 peptidase
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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
F16D
residue involved in most of the peptide interactions, almost complete loss of catalytic activity
F303W
mutation does not cause significant destabilizing or stabilizing effects on the thermal denaturation
F331W
mutation in proease domain, mutation does not cause significant destabilizing or stabilizing effects on the thermal denaturation
G230A
residue involved in most of the peptide interactions, about 12% of wild-type catalytic efficiency
G399S
L367W
mutation does not cause significant destabilizing or stabilizing effects on the thermal denaturation
L377W
mutation in PDZ domain, mutation does not cause significant destabilizing or stabilizing effects on the thermal denaturation
N216A/S219A
residues involved in most of the peptide interactions, about 33% of wild-type catalytic efficiency
R337L
mutant has an increased activity at all temperatures tested, higher affinity for the substrate and a higher turnover rate
R432L
S142A
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considerably less phosphorylated by p38gamma in vitro. Markedly lower protease activity than its acidic counterpart
S142D
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
S306A
S400A
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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
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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
S276C
S306A
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
A141S
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affects the enzymatic activity of the protease, associated with the development of Parkinsons disease
G399S
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affects the enzymatic activity of the protease, associated with the development of Parkinsons disease
G399S
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mutation in HtrA2 identified in patients with Parkinson's disease, ability of p38gamma to phosphorylate the peptide is decreased
R432L
variant has an increased activity with beta-casein and the peptide Ala(7-methoxycoumarin-4-acetic acid)-IRRVSYSF-(5-amido-2-nitro benzoic acid) at various temperatures
S142D
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phospho-mimetic HtrA2-mutant, increases the basal ability of HtrA2 to cleave a fluorogenic substrate peptide by about 2fold
S142D
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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
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phospho-mimetic HtrA2-mutant, increases the basal ability of HtrA2 to cleave a fluorogenic substrate peptide by about 3fold
S400D
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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
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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
S276C
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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
additional information
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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
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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
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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
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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
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HtrA2 knockout MEFs, no endogenous PINK1. Show decreased mitochondrial membrane potential
additional information
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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
