Any feedback?
Information on EC 3.4.21.107 - peptidase Do and Organism(s) Escherichia coli and UniProt Accession P39099
for references in articles please use BRENDA:EC3.4.21.107Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
3.4.21.107 peptidase DoSpecify your search results
Word Map
- 3.4.21.107
- degeneration
-
macular
- cerebral
- retinal
- infarct
- neovascularization
- vessel
- parkinsonism
- leukoencephalopathy
-
arteriopathy
-
subcortical
-
carasil
- xiap
-
misfolded
- choroid
- osteoarthritis
- maculopathy
- preeclampsia
-
polypoidal
- pink1
-
acuity
- alopecia
-
drusen
- medicine
-
small-vessel
-
extracytoplasmic
-
amd-associated
-
notch3
- spondylosis
-
transmigration
-
ranibizumab
- biotechnology
- molecular biology
The taxonomic range for the selected organisms is: Escherichia coli
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
acts on substrates that are at least partially unfolded. The cleavage site P1 residue is normally between a pair of hydrophobic residues, such as Val-/-Val
Synonyms
htra1, htra2, htra3, htra4, serine protease htra1, high-temperature requirement a, htra protease, high temperature requirement a, serine protease htra, degp protease, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
DegP
HtrA
protease do
DegP
-
-
HtrA
-
-
protease do
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
cleavage of C-N-linkage
hydrolysis of peptide bond
-
-
cleavage of C-N-linkage
-
-
CAS REGISTRY NUMBER
COMMENTARY
161108-11-8
-
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
alpha-lactalbumin + H2O
?
-
acts on the fully unfolded protein but not on the native form
-
?
citrate synthase + H2O
?
-
acts on the thermally unfolded synthase but not on the native form
-
?
colicin A lysis protein + H2O
?
-
i.e. pCal, hydrolyses the acylated precursor form, cleaves at two sites near the C-terminal end to give two truncated proteins which are matured into two truncated Cals
-
?
insulin beta-chain + H2O
?
-
oxidized beta-chain which is fully unfolded
-
?
outer membrane protein A + H2O
?
in contrast to misfolded model substrates, which are degraded within a few min, the co-purified outer-membrane proteins are stable. Even in the presence of externally applied proteases, the bound outer-membrane proteins are almost entirely resistant to proteolytic degradation. DegP functions as a geniune chaperone
-
-
?
outer membrane protein C + H2O
?
in contrast to misfolded model substrates, which are degraded within a few min, the co-purified outer-membrane proteins are stable. Even in the presence of externally applied proteases, the bound outer-membrane proteins are almost entirely resistant to proteolytic degradation. DegP functions as a geniune chaperone
-
-
?
outer membrane protein F + H2O
?
in contrast to misfolded model substrates, which are degraded within a few min, the co-purified outer-membrane proteins are stable. Even in the presence of externally applied proteases, the bound outer-membrane proteins are almost entirely resistant to proteolytic degradation. DegP functions as a geniune chaperone
-
-
?
PVFNTLPMMGKASPV-4-nitroanilide + H2O
PVFNTLPMMGKASPV + 4-nitroaniline
-
-
-
-
?
reaction centre protein D2 + H2O
?
-
substrate of isoforms DEG1, DEG5, DEG7 and DEG8
-
-
?
VFNTLPMMGKASPV-4-nitroanilide + H2O
VFNTLPMMGKASPV + 4-nitroaniline
-
-
-
-
?
beta-casein + H2O
?
-
cleaves beta-casein yielding several polypeptide fragments
-
?
FkpA + H2O
?
-
periplasmic peptidyl-prolyl cistrans isomerase, chaperone
-
-
?
FkpA + H2O
?
-
periplasmic peptidyl-prolyl cis-trans isomerase, chaperone
-
-
?
Lysozyme + H2O
?
-
can only be digested in the presence of reducing agents
-
?
malate dehydrogenase + H2O
?
-
acts on the thermally unfolded protein but not on the native form
-
?
Protein + H2O
?
-
cleaves model substrates at discrete Val/Xaa or Ile/Xaa sites
-
?
Protein + H2O
?
-
cleaves preferably at hydrophobic side chains at the P1 position
-
?
Protein + H2O
?
-
denatured proteins aggregate to form a distinct S fraction, one third of the isolated S fraction is converted to trichloroacetic acid-soluble products
-
?
Protein + H2O
?
-
denatured proteins aggregate to form a distinct S fraction, one third of the isolated S fraction is converted to trichloroacetic acid-soluble products, enzyme has a preference for valine or isoleucine as the residue preceding the cleavage site
-
?
Protein + H2O
?
-
enzyme recognizes an ssrA-encoded peptide tag which is tagged to misfolded proteins or protein fragments
-
?
additional information
?
-
-
acts on substrates that are at least partially unfolded, does not cleave stably folded proteins, acts as a general chaperone forming stable complexes with several misfolded proteins
-
?
additional information
?
-
-
no substrates are: bovine serum albumin, ovalbumin, globin, insulin and other peptides that are routinely used as protease substrates
-
?
additional information
?
-
-
no substrates are: native bovine serum albumin, insulin, growth hormone or a variety of commonly used peptide substrates
-
?
additional information
?
-
-
heat shock serine protease that degrades misfolded proteins at high temperatures
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, enzyme is indispensable for bacterial survival at elevated temperatures
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, enzyme is indispensable for bacterial survival at temperatures above 42°C
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, enzyme is indispensable for bacterial survival at temperatures above 42°C
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, participate in removal of aggregated proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, switches from chaperone to protease function in a temperature-dependent manner
-
?
additional information
?
-
-
involved in the degradation of denatured and unfolded proteins
-
?
additional information
?
-
-
involved in the degradation of misfolded proteins
-
?
additional information
?
-
-
involved in the degradation of unfolded proteins
-
?
additional information
?
-
-
unable to cleave inhibitor of apoptosis protein
-
-
?
additional information
?
-
-
allosteric activation of DegP by stress signals during bacterial protein quality control, regulation mechanism, pathway scheme, overview
-
-
?
additional information
?
-
-
HtrA inhibits the unfolded lysozyme substrate aggregation over the range of temperatures at 30-45°C, HtrA is able to bind to the denatured polypeptides and as a consequence limits their ability to form large aggregates, overview, HtrA may protect the bacterial cells from deleterious effects of heat shock not only by degrading the damaged proteins but by combination of the proteolytic and chaperoning activities
-
-
?
additional information
?
-
-
HtrA shows chaperone-like activity, overview
-
-
?
additional information
?
-
-
when unfolded proteins bind to CpxP, DegP efficiently degrades this protein complex
-
-
?
additional information
?
-
-
almost no activity towards SDAEFRHDSGYEV-4-nitroanilide, SDAEFRHDSGYEV-4-nitroanilide, SGRVVPGYGHA-4-nitroanilide, SPLPEGV-4-nitroanilide , GLATGNVSTAELQDATPA-4-nitroanilide, KGKNSGSGATPV-4-nitroanilide, KGASVPGAGLV-4-nitroanilide, SPAKGGEEPLPEGV-4-nitroanilide, and benzoyl-L-Arg-4-nitroanilide
-
-
?
additional information
?
-
-
identification of beta-barrel outer membrane proteins, OMPs, as major natural substrates by photo-crosslinking using non-natural amino acid DiZPK, 3-(3-methyl-3H-diazirine-3-yl)-propaminocarbonyl-Nepsilon-L-lysine, as the photo-crosslinker. Isoform DegP primarily functions as a protease, at both low and high temperatures, to eliminate unfolded outer membrane proteins, with hardly any appreciable chaperone activity in cells. The toxic and cell membrane-damaging misfolded outer membrane proteins would accumulate in DegP-lacking cells cultured under heat shock conditions
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
FkpA + H2O
?
-
periplasmic peptidyl-prolyl cistrans isomerase, chaperone
-
-
?
outer membrane protein A + H2O
?
in contrast to misfolded model substrates, which are degraded within a few min, the co-purified outer-membrane proteins are stable. Even in the presence of externally applied proteases, the bound outer-membrane proteins are almost entirely resistant to proteolytic degradation. DegP functions as a geniune chaperone
-
-
?
outer membrane protein C + H2O
?
in contrast to misfolded model substrates, which are degraded within a few min, the co-purified outer-membrane proteins are stable. Even in the presence of externally applied proteases, the bound outer-membrane proteins are almost entirely resistant to proteolytic degradation. DegP functions as a geniune chaperone
-
-
?
outer membrane protein F + H2O
?
in contrast to misfolded model substrates, which are degraded within a few min, the co-purified outer-membrane proteins are stable. Even in the presence of externally applied proteases, the bound outer-membrane proteins are almost entirely resistant to proteolytic degradation. DegP functions as a geniune chaperone
-
-
?
reaction centre protein D2 + H2O
?
-
substrate of isoforms DEG1, DEG5, DEG7 and DEG8
-
-
?
additional information
?
-
-
heat shock serine protease that degrades misfolded proteins at high temperatures
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, enzyme is indispensable for bacterial survival at elevated temperatures
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, enzyme is indispensable for bacterial survival at temperatures above 42°C
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, enzyme is indispensable for bacterial survival at temperatures above 42°C
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, participate in removal of aggregated proteins
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, switches from chaperone to protease function in a temperature-dependent manner
-
?
additional information
?
-
-
involved in the degradation of denatured and unfolded proteins
-
?
additional information
?
-
-
involved in the degradation of misfolded proteins
-
?
additional information
?
-
-
involved in the degradation of unfolded proteins
-
?
additional information
?
-
-
allosteric activation of DegP by stress signals during bacterial protein quality control, regulation mechanism, pathway scheme, overview
-
-
?
additional information
?
-
-
HtrA inhibits the unfolded lysozyme substrate aggregation over the range of temperatures at 30-45°C, HtrA is able to bind to the denatured polypeptides and as a consequence limits their ability to form large aggregates, overview, HtrA may protect the bacterial cells from deleterious effects of heat shock not only by degrading the damaged proteins but by combination of the proteolytic and chaperoning activities
-
-
?
additional information
?
-
-
when unfolded proteins bind to CpxP, DegP efficiently degrades this protein complex
-
-
?
additional information
?
-
-
identification of beta-barrel outer membrane proteins, OMPs, as major natural substrates by photo-crosslinking using non-natural amino acid DiZPK, 3-(3-methyl-3H-diazirine-3-yl)-propaminocarbonyl-Nepsilon-L-lysine, as the photo-crosslinker. Isoform DegP primarily functions as a protease, at both low and high temperatures, to eliminate unfolded outer membrane proteins, with hardly any appreciable chaperone activity in cells. The toxic and cell membrane-damaging misfolded outer membrane proteins would accumulate in DegP-lacking cells cultured under heat shock conditions
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
not inhibited by SGRVVPGYGHA-chloromethylketone and IWNTLNSGRVVPGTGHA-chloromethylketone
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
OMP C-terminal tripeptide YYF-COOH
-
activation less efficient as compared to 15 residue presenilin-1 peptide
additional information
-
largely indpependent of activating compounds such as reducing agents
-
additional information
-
low osmolarity conditions result in HtrA repression together with the nucleoid associated proteins H-NS and HhA
-
additional information
-
allosteric activation of DegP by stress signals during bacterial protein quality control, DegP activation is based on an interaction of the activating peptide with PDZ domains
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.001
-
using PMMGKASPV-4-nitroanilide as substrate, in 50 mM NaH2PO4, pH 8.0, temperature not specified in the publication
0.018
0.032
-
using VFNTLPMMGKASPV-4-nitroanilide as substrate, in 50 mM NaH2PO4, pH 8.0, temperature not specified in the publication
0.473
-
using DPMFKLV-4-nitroanilide as substrate, in 50 mM NaH2PO4, pH 8.0, temperature not specified in the publication
additional information
-
DegP protease exhibits a concentration effect: an 8fold increase in the concentration of DegP results in an 2.4fold increase in the specific protease activity
0.018
-
using PVFNTLPMMGKASPV-4-nitroanilide as substrate, in 50 mM NaH2PO4, pH 8.0, temperature not specified in the publication
0.018
-
using SPMFKGV-4-nitroanilide as substrate, in 50 mM NaH2PO4, pH 8.0, temperature not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20
-
reduced alkaline phosphatase is efficiently degraded at 20°C, both in vivo and in vitro. The cleavage is most efficient in the case of a C57A/C69A mutant, lacking its internal SS bond
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20 - 30
-
almost no activity below 20°C, activity rapidly increases above 30°C
37 - 45
44
-
at 44 °C function of DegP in mutant strain CLC198 can be complemented by HtrA2
37 - 45
-
no change of cell density of wild type, cell density of the mutant rapidly falls, protease Do essential for the cell's survival at high temperatures
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
bowl-shaped DegP assemblies on membranes have higher proteolytic activity but lower chaperone-Like activity
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
-
DegP can act as a chaperone and a protease at the same time. Deg P is a key player in extracytoplasmic protein quality control and exhibits features of a protective factor during protein folding stress. As a chaperone, DegP refolds periplasmic amylase MalS and the artificial substrate citrate synthase
physiological function
-
the chaperone activity but not the protease activity of DegP is required for growth of ssrA-deficient cells at high themperature
physiological function
-
HtrA acts as chaperone and protease. DEG1 interacts with the reaction centre protein D2 and assists in the assembly of photosystem II
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
300000
46000
50000
54000
50000
-
12 * 50000, SDS-PAGE, enzyme can exist in two oligomeric forms which are interconvertible
50000
-
6 * 50000, SDS-PAGE, enzyme can exist in two oligomeric forms which are interconvertible
54000
-
10 * 54000, SDS-PAGE, enzyme exists in 3 different forms: pentamer, hexamer and decamer
54000
-
5 * 54000, SDS-PAGE, enzyme exists in 3 different forms: pentamer, hexamer and decamer
54000
-
6 * 54000, SDS-PAGE, enzyme exists in 3 different forms: pentamer, hexamer and decamer
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
decamer
-
10 * 54000, SDS-PAGE, enzyme exists in 3 different forms: pentamer, hexamer and decamer
dodecamer
hexamer
multimer
oligomer
pentamer
-
5 * 54000, SDS-PAGE, enzyme exists in 3 different forms: pentamer, hexamer and decamer
trimer
dodecamer
-
12 * 50000, SDS-PAGE, enzyme can exist in two oligomeric forms which are interconvertible
dodecamer
-
consists of two stacks of hexameric rings, SDS-PAGE, cross-linking experiments
hexamer
-
6 * 50000, SDS-PAGE, enzyme can exist in two oligomeric forms which are interconvertible
hexamer
-
6 * 54000, SDS-PAGE, enzyme exists in 3 different forms: pentamer, hexamer and decamer
hexamer
two trimers for a hexameric structure by staggered association
hexamer
crystal structures suggest that HtrA proteins differ in their molecular architecture, ranging from trimers with surface-accessible active sites to hexamers
hexamer
purified wild type DegP exists mainly as hexamers (dimers of trimers) in solution
multimer
-
DegP activates its chaperone and protease functions via formation of large cage-like 12- and 24-mers after binding to substrate proteins. Cryo-electron microscopic and biochemical studies reveal that both oligomers are consistently assembled by blocks of DegP trimers, via pairwise PDZ1-PDZ2 interactions between neighboring trimers. Such interactions simultaneously eliminate the inhibitory effects of the PDZ2 domain. Additionally, both DegP oligomers are also observed in extracts of Escherichia. coli cells, strongly implicating their physiological importance
multimer
gel filtration shows three DegP oligomers, namely the 6-mer (DegP6), the 12-mer (DegP12) and the 24-mer (DegP24), of which the two larger particles had additional proteins bound. Binding of misfolded proteins transforms hexameric DegP into large, catalytically active 12-meric and 24-meric multimers. A structural analysis of these particles reveal that DegP represents a protein packaging device whose central compartment is adaptable to the size and concentration of substrate. Moreover, the inner cavity serves antagonistic functions
oligomer
-
largest complexes are dodecamers, probably formed by dimerization of trimers, gel filtration experiments
oligomer
-
DegP protease chaperone system is regulated by oligomer conversion from the resting hexamer into the catalytically active 12mer and 24mer that capture and digest misfolded proteins
oligomer
-
x * about 50000, SDS-PAGE. In the absence of substrate, DegP oligomerizes as a hexameric cage but in its presence DegP reorganizes into active 12- and 24-mer cages. The size of the substrate molecule is the main factor conditioning the oligomeric state adopted by the enzyme, while ther factors such as temperature, do not influence the oligomeric state
trimer
crystal structures suggest that HtrA proteins differ in their molecular architecture, ranging from trimers with surface-accessible active sites to hexamers
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
enzyme is derived by cleavage of the first 26 amino acids of the pre-HtrA precursor polypeptide
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
a theoretical model of the three-dimensional structure of the LA loop as per the resting state of enzyme HtrA. hydrophobic interactions connect the LA loops of the hexamer and polar contacts between the LA', i.e. the LA loop on an opposite subunit, and L1 loops on opposite subunits. Disturbance of these interactions causes the stimulation of HtrA proteolytic activity. LA loops contribute to the preservation of the integrity of the HtrA oligomer and to the stability of the monomer
crystal structure of the DegP24 multimer-outer membrane protein complex is solved by the single-wavelength anomalous dispersion method: The 24-mer of DegP forms a spherical shell with 432 symmetry. In the crystal structure of DegP24, eight trimers are located at the vertices of an octahedron that assembles a protein shell of about 31 A thickness enclosing a large internal cavity about 110 A in diameter
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C57A/C69A
-
mutant represents a completely reduced HtrA being unable to form the intramolecular S-S bond. Mutant very efficiently degrades alkaline phosphatase at 20°C which is very pronounced compared to wild-type. Thus, the reduction of HtrAs disulfide bridge may facilitate the activation of the protease
C57S/C69S
-
mutant enzyme is less stable, in contrast to wild-type enzyme the mutant protein is autocleaved even without reducing agents
D221A
mutant displays reduced peptide Tyr-Tyr-Phe-stimulated cleavage activity
D221A/H198P
mutant displays more than 65% of peptide Tyr-Tyr-Phe-stimulated cleavage activity of mutant H198P
D52A
mutation within LA loop. Mutation has no impact on the proteolytic activity of HtrA
D53A
mutation within LA loop. Mutation has no impact on the proteolytic activity of HtrA
DELTA360-448
-
mutant lacking the PDZ2 domain. Results of gel filtration reveal that the removal of the whole PDZ2 domain, results in the formation of only trimers that form neither the hexamers nor the 12- or 24-mers. Such a mutant trimeric form of DegP exhibits both chaperone-like and protease activities at a level comparable to that of the wild-type protein. Mutant shows no concentration effect compared to wild-type
DELTA440-448
-
the removal of the beta26 strand on the C terminus of the PDZ2 domain (residues 440-448), which is shown to directly interact with the neighboring PDZ1 domain, does not disrupt the formation of DegP hexamers but prevents their conversion to the 12- or 24-mers. Mutant protein exhibits significantly lower chaperone-like and protease activity, suggesting an inhibitory role of the PDZ2 domain for DegP to exhibit chaperone and protease activities. Mutant shows no concentration effect compared to wild-type
F234A
mutagenic analysis of allosteric activation, less than 2% of peptide Tyr-Tyr-Phe-stimulated wild-type activity
F46Y
mutation within LA loop. Mutant displays increased activity with substrate beta-casein
F49Y/F50Y
mutation within LA loop. Mutant displays increased activity with substrate beta-casein
F56S
mutation within LA loop. Mutation has no impact on the proteolytic activity of HtrA
F63Y
mutation within LA loop. Mutant displays increased activity with substrate beta-casein
F68Y
mutation within LA loop. Mutant displays increased activity with substrate beta-casein
H105R
-
loss of protease activity, no change in secondary structure
H198P
mutation stabilizes active DegS and increases the proteolytic activity of otherwise wild-type DegSabout 6-fold under assay conditions
I179A
mutant displays reduced peptide Tyr-Tyr-Phe-stimulated cleavage activity
I179A/H198P D221A
mutant displays more than 65% of peptide Tyr-Tyr-Phe-stimulated cleavage activity of mutant H198P
I228D
-
the mutation does not markedly affect the proteolytic activity of HtrA
I232A
mutagenic analysis of allosteric activation, less than 2% of peptide Tyr-Tyr-Phe-stimulated wild-type activity
K305A/K379A/K381A/K416A
to monitor directly the influence of the PDZ domains on lipid binding, mutants in which the surface-exposed lysine residues are replaced by alanine: Dose-response experiments reveal that the lipid affinity of the DegP 24-mer mutant is significantly decreased. Thus DegP could function as a periplasmic macropore, allowing the protected diffusion of outer-membrane protein precursors from the inner membrane to the outer membrane
K379E/K381E/K416E
to monitor directly the influence of the PDZ domains on lipid binding, mutants in which the surface-exposed lysine residues are replaced by glutamate alanine: Dose-response experiments reveal that the lipid affinity of the DegP 24-mer mutant is almost entirely impaired. Thus DegP could function as a periplasmic macropore, allowing the protected diffusion of outer-membrane protein precursors from the inner membrane to the outer membrane
L164A
mutagenic analysis of allosteric activation, less than 2% of peptide Tyr-Tyr-Phe-stimulated wild-type activity
N197A
mutagenic analysis of allosteric activation, less than 2% of peptide Tyr-Tyr-Phe-stimulated wild-type activity
P161A
mutagenic analysis of allosteric activation, less than 2% of peptide Tyr-Tyr-Phe-stimulated wild-type activity
P43G
mutation within LA loop. At 20 °C the activities of are similar to wild-type, whereas at higher temperatures of 35 or 45 °C the mutant shows a higher activity
Q187A
mutant displays reduced peptide Tyr-Tyr-Phe-stimulated cleavage activity
Q187A/H198P
mutant displays more than 65% of peptide Tyr-Tyr-Phe-stimulated cleavage activity of mutant H198P
Q191A
mutagenic analysis of allosteric activation, less than 2% of peptide Tyr-Tyr-Phe-stimulated wild-type activity
Q47L
mutation within LA loop. Mutant displays increased activity with substrate beta-casein
Q64A
mutation within LA loop. Mutation has no impact on the proteolytic activity of HtrA
Q64I
mutation within LA loop. Mutation has no impact on the proteolytic activity of HtrA
Q70A
mutation within LA loop. Mutant displays increased activity with substrate beta-casein
R44A
mutation within LA loop. Mutation leads to dramatic autocleavage of the protein, occurring both within cells and during their preparation
S210A
S54A
mutation within LA loop. Mutation has no impact on the proteolytic activity of HtrA
T167V
mutagenic analysis of allosteric activation, less than 2% of peptide Tyr-Tyr-Phe-stimulated wild-type activity
T169A
mutagenic analysis of allosteric activation, less than 2% of peptide Tyr-Tyr-Phe-stimulated wild-type activity
Y162A
mutagenic analysis of allosteric activation, less than 2% of peptide Tyr-Tyr-Phe-stimulated wild-type activity
additional information
S210A
-
loss of protease activity, no change in secondary structure
S210A
-
experimental studies are carried out using protease deficient mutant
S210A
-
mutant S210A, lacking proteolytic activity but retaining chaperone activity is overexpressed in mutant strain htrAdsbA, lacking the functional htrA gene and the functional DsbA/DsbB oxidoreductase system, which: the presence of mutant S210A increases the survival rate of the htrAdsbA double-mutant bacteria. Thus, the proteolytic activity of HtrA seems to play an important role in bacterial cells even at low temperatures (30°C), at which the chaperone function is proposed as being dominant
S210A
proteolytically inactive, the mutant does not show significant changes of the secondary structure at the temperature range 20-45°C
additional information
-
disruption of the ptd gende to obtain lack of activity of protease Do, mutant with prolonged lag period, reduced ability to degrade cell proteins and unable to survive at high temperatures
additional information
-
HtrA mutant S210A suppresses the temperature-sensitive phenotype of the htrA mutant and alleviates the lethality of htrA bacteria at high temperatures
additional information
-
a htrAdsbA double-mutant, lacking the functional htrA gene and the functional DsbA/DsbB oxidoreductase system shows a dramatically inhibited growth rate in the presence of 7 mM DTT when compared to mutant strain dsbA containing a single mutation in the DsbA/DsbB oxidoreductase system, indicating that htrA gene is important for survival of the dsbA mutant in the reducing environment
additional information
in degP-null mutant strains the levels of outer-membrane protein A, outer-membrane protein F and to smaller extent also outer-membrane protein C are decreased, indicating an active role of DegP in the outer-membrane protein biogenesis
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20 - 45
the proteolysis of casein at 20°C is negligible, then it increases in almost linear fashion up to 45°C. At the temperature range of 40-45°C, the activity is approximately 1.5fold higher than at 37°C
additional information
-
interaction with phosphatidylgycerol leads to a remarkable decrease in the thermal stability
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
enzyme cleaves itself under reducing conditions in the presence of 2-mercaptoethanol or dithiothreitol
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cloned into a Bluescript plasmid and overexpressed in Escherichia coli DH1, disrupted gene transformed to Escherichia coli Jc7623
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
RpoE is released from the membrane to function as a sigma factor that induces degP expression. On the protein level, DegP activity is upregulated by C-termini of omps as well as misfolded periplasmic proteins
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
biotechnology
-
htrA mutants show improved expression of envelope-associated proteins
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Swamy, K.H.; Chung, C.H.; Goldberg, A.L.
Isolation and characterization of protease do from Escherichia coli, a large serine protease containing multiple subunits
Arch. Biochem. Biophys.
224
543-554
1983
Escherichia coli
Skorko-Glonek, J.; Zurawa, D.; Tanfani, F.; Scire, A.; Wawrzynow, A.; Narkiewicz, J.; Bertoli, E.; Lipinska, B.
The N-terminal region of HtrA heat shock protease from Escherichia coli is essential for stabilization of HtrA primary structure and maintaining of its oligomeric structure
Biochim. Biophys. Acta
1649
171-182
2003
Escherichia coli
Cavard, D.
Role of DegP protease on levels of various forms of colicin A lysis protein
FEMS Microbiol. Lett.
125
173-178
1995
Escherichia coli
Skorko-Glonek, J.; Wawrzynow, A.; Krzewski, K.; Kurpierz, K.; Lipinska, B.
Site-directed mutagenesis of the HtrA (DegP) serine protease, whose proteolytic activity is indispensable for Escherichia coli survival at elevated temperatures
Gene
163
47-52
1995
Escherichia coli
Strauch, K.L.; Johnson, K.; Beckwith, J.
Characterization of degP, a gene required for proteolysis in the cell envelope and essential for growth of Escherichia coli at high temperature
J. Bacteriol.
171
2689-2696
1989
Escherichia coli
Lipinska, B.; Zylicz, M.; Georgopoulos, C.
The HtrA (DegP) protein, essential for Escherichia coli survival at high temperatures, is an endopeptidase
J. Bacteriol.
172
1791-1797
1990
Escherichia coli
Kolmar, H.; Waller, P.R.; Sauer, R.T.
The DegP and DegQ periplasmic endoproteases of Escherichia coli: specificity for cleavage sites and substrate conformation
J. Bacteriol.
178
5925-5929
1996
Escherichia coli
Jones, C.H.; Dexter, P.; Evans, A.K.; Liu, C.; Hultgren, S.J.; Hruby, D.E.
Escherichia coli DegP protease cleaves between paired hydrophobic residues in a natural substrate: the PapA pilin
J. Bacteriol.
184
5762-5771
2002
Escherichia coli
Skorko-Glonek, J.; Krzewski, K.; Lipinska, B.; Bertoli, E.; Tanfani, F.
Comparison of the structure of wild-type HtrA heat shock protease and mutant HtrA proteins. A Fourier transform infrared spectroscopic study
J. Biol. Chem.
270
11140-11146
1995
Escherichia coli
Skorko-Glonek, J.; Lipinska, B.; Krzewski, K.; Zolese, G.; Bertoli, E.; Tanfani, F.
HtrA heat shock protease interacts with phospholipid membranes and undergoes conformational changes
J. Biol. Chem.
272
8974-8982
1997
Escherichia coli
Spiers, A.; Lamb, H.K.; Cocklin, S.; Wheeler, K.A.; Budworth, J.; Dodds, A.L.; Pallen, M.J.; Maskell, D.J.; Charles, I.G.; Hawkins, A.R.
PDZ domains facilitate binding of high temperature requirement protease A (HtrA) and tail-specific protease (Tsp) to heterologous substrates through recognition of the small stable RNA A (ssrA)-encoded peptide
J. Biol. Chem.
277
39443-39449
2002
Escherichia coli
Kim, K.I.; Park, S.C.; Kang, S.H.; Cheong, G.W.; Chung, C.H.
Selective degradation of unfolded proteins by the self-compartmentalizing HtrA protease, a periplasmic heat shock protein in Escherichia coli
J. Mol. Biol.
294
1363-1374
1999
Escherichia coli
Clausen, T.; Southan, C.; Ehrmann, M.
The HtrA family of proteases: implications for protein composition and cell fate
Mol. Cell
10
443-455
2002
Arabidopsis thaliana, Escherichia coli, Homo sapiens, Rickettsia sp.
Laskowska, E.; Kuczynska-Wisnik, D.; Skorko-Glonek, J.; Taylor, A.
Degradation by proteases Lon, Clp and HtrA, of Escherichia coli proteins aggregated in vivo by heat shock; HtrA protease action in vivo and in vitro
Mol. Microbiol.
22
555-571
1996
Escherichia coli
Pallen, M.J.; Wren, B.W.
The HtrA family of serine proteases
Mol. Microbiol.
26
209-221
1997
Escherichia coli, Salmonella enterica subsp. enterica serovar Typhimurium, Yersinia enterocolitica
Sassoon, N.; Arie, J.P.; Betton, J.M.
PDZ domains determine the native oligomeric structure of the DegP (HtrA) protease
Mol. Microbiol.
33
583-589
1999
Escherichia coli
Krojer, T.; Garrido-Franco, M.; Huber, R.; Ehrmann, M.; Clausen, T.
Crystal structure of DegP (HtrA) reveals a new protease-chaperone machine
Nature
416
455-459
2002
Escherichia coli (P0C0V0)
Day, C.L.; Hinds, M.G.
HtrA-a renaissance protein
Structure
10
737-739
2002
Mammalia, Escherichia coli (P0C0V0), Escherichia coli
Brndsted, L.; Andersen, M.T.; Parker, M.; Jorgensen, K.; Ingmer, H.
The HtrA protease of Campylobacter jejuni is required for heat and oxygen tolerance and for optimal interaction with human epithelial cells
Appl. Environ. Microbiol.
71
3205-3212
2005
Campylobacter jejuni, Escherichia coli, Campylobacter jejuni NCTC 11168
Seol, J.H.; Woo, S.K.; Jung, E.M.; Yoo, S.J.; Lee, C.S.; Kim, K.J.; Tanaka, K.; Ichihara, A.; Ha, D.B.; Chung, C.H.
Protease Do is essential for survival of Escherichia coli at high temperatures: its identity with the htrA gene product
Biochem. Biophys. Res. Commun.
176
730-736
1991
Escherichia coli
Zhang, X.; Chang, Z
Temperature dependent protease activity and structural properties of human HtrA2 protease
Biochemistry (Moscow)
69
687-692
2004
Escherichia coli
Forns, N.; Juarez, A.; Madrid, C.
Osmoregulation of the HtrA (DegP) protease of Escherichia coli: An HhaH-NS complex represses HtrA expression at low osmolarity
FEMS Microbiol. Lett.
251
75-80
2005
Escherichia coli
Sebert, M.E.; Patel, K.P.; Plotnick, M.; Weiser, J.N.
Pneumococcal HtrA protease mediates inhibition of competence by the CiaRH two-component signaling system
J. Bacteriol.
187
3969-3979
2005
Streptococcus pneumoniae, Escherichia coli
Gupta, S.; Singh, R.; Datta, P.; Zhang, Z.; Orr, C.; Lu, Z.; Dubois, G.; Zervos, A.S.; Meisler, M.H.; Srinivasula, S.M.; Fernandes-Alnemri, T.; Alnemri, E.S.
The C-terminal tail of presenelin regulates Omi/HtrA2 protease activity
J. Biol. Chem.
279
45844-45854
2004
Escherichia coli
Meltzer, M.; Hasenbein, S.; Hauske, P.; Kucz, N.; Merdanovic, M.; Grau, S.; Beil, A.; Jones, D.; Krojer, T.; Clausen, T.; Ehrmann, M.; Kaiser, M.
Allosteric activation of HtrA protease DegP by stress signals during bacterial protein quality control
Angew. Chem. Int. Ed. Engl.
47
1332-1334
2008
Escherichia coli
Skorko-Glonek, J.; Laskowska, E.; Sobiecka-Szkatula, A.; Lipinska, B.
Characterization of the chaperone-like activity of HtrA (DegP) protein from Escherichia coli under the conditions of heat shock
Arch. Biochem. Biophys.
464
80-89
2007
Escherichia coli
Skorko-Glonek, J.; Sobiecka-Szkatula, A.; Narkiewicz, J.; Lipinska, B.
The proteolytic activity of the HtrA (DegP) protein from Escherichia coli at low temperatures
Microbiology
154
3649-3658
2008
Escherichia coli
Krojer, T.; Sawa, J.; Schaefer, E.; Saibil, H.R.; Ehrmann, M.; Clausen, T.
Structural basis for the regulated protease and chaperone function of DegP
Nature
453
885-890
2008
Escherichia coli (P0C0V0)
Jiang, J.; Zhang, X.; Chen, Y.; Wu, Y.; Zhou, Z.H.; Chang, Z.; Sui, S.F.
Activation of DegP chaperone-protease via formation of large cage-like oligomers upon binding to substrate proteins
Proc. Natl. Acad. Sci. USA
105
11939-11944
2008
Escherichia coli
Sobiecka-Szkatula, A.; Gieldon, A.; Scire, A.; Tanfani, F.; Figaj, D.; Koper, T.; Ciarkowski, J.; Lipinska, B.; Skorko-Glonek, J.
The role of the L2 loop in the regulation and maintaining the proteolytic activity of HtrA (DegP) protein from Escherichia coli
Arch. Biochem. Biophys.
500
123-130
2010
Escherichia coli
Sobiecka-Szkatula, A.; Polit, A.; Scire, A.; Gieldon, A.; Tanfani, F.; Szkarlat, Z.; Ciarkowski, J.; Zurawa-Janicka, D.; Skorko-Glonek, J.; Lipinska, B.
Temperature-induced conformational changes within the regulatory loops L1-L2-LA of the HtrA heat-shock protease from Escherichia coli
Biochim. Biophys. Acta
1794
1573-1582
2009
Escherichia coli (P0C0V0), Escherichia coli
Hauske, P.; Meltzer, M.; Ottmann, C.; Krojer, T.; Clausen, T.; Ehrmann, M.; Kaiser, M.
Selectivity profiling of DegP substrates and inhibitors
Bioorg. Med. Chem.
17
2920-2924
2009
Escherichia coli
Ono, K.; Kutsukake, K.; Abo, T.
Suppression by enhanced RpoE activity of the temperature-sensitive phenotype of a degP ssrA double mutant in Escherichia coli
Genes Genet. Syst.
84
15-24
2009
Escherichia coli
Shen, Q.T.; Bai, X.C.; Chang, L.F.; Wu, Y.; Wang, H.W.; Sui, S.F.
Bowl-shaped oligomeric structures on membranes as DegPs new functional forms in protein quality control
Proc. Natl. Acad. Sci. USA
106
4858-4863
2009
Escherichia coli (P0C0V0)
Meltzer, M.; Hasenbein, S.; Mamant, N.; Merdanovic, M.; Poepsel, S.; Hauske, P.; Kaiser, M.; Huber, R.; Krojer, T.; Clausen, T.; Ehrmann, M.
Structure, function and regulation of the conserved serine proteases DegP and DegS of Escherichia coli
Res. Microbiol.
160
660-666
2009
Escherichia coli
Clausen, T.; Kaiser, M.; Huber, R.; Ehrmann, M.
HTRA proteases: regulated proteolysis in protein quality control
Nat. Rev. Mol. Cell Biol.
12
152-162
2011
Arabidopsis thaliana, Escherichia coli, Helicobacter pylori, Homo sapiens, Streptococcus mutans
Iwanczyk, J.; Leong, V.; Ortega, J.
Factors defining the functional oligomeric state of Escherichia coli DegP protease
PLoS ONE
6
e18944
2011
Escherichia coli
Ge, X.; Wang, R.; Ma, J.; Liu, Y.; Ezemaduka, A.N.; Chen, P.R.; Fu, X.; Chang, Z.
DegP primarily functions as a protease for the biogenesis of beta-barrel outer membrane proteins in the Gram-negative bacterium Escherichia coli
FEBS J.
281
1226-1240
2014
Escherichia coli
Hoy, B.; Geppert, T.; Boehm, M.; Reisen, F.; Plattner, P.; Gadermaier, G.; Sewald, N.; Ferreira, F.; Briza, P.; Schneider, G.; Backert, S.; Wessler, S.
Distinct roles of secreted HtrA proteases from gram-negative pathogens in cleaving the junctional protein and tumor suppressor E-cadherin
J. Biol. Chem.
287
10115-10120
2012
Campylobacter jejuni, Shigella flexneri, Escherichia coli (B7UIK8), Escherichia coli E2348/69 (B7UIK8)
Figaj, D.; Gieldon, A.; Polit, A.; Sobiecka-Szkatula, A.; Koper, T.; Denkiewicz, M.; Banecki, B.; Lesner, A.; Ciarkowski, J.; Lipinska, B.; Skorko-Glonek, J.
The LA loop as an important regulatory element of the HtrA (DegP) protease from Escherichia coli: structural and functional studies
J. Biol. Chem.
289
15880-15893
2014
Escherichia coli (P0C0V0), Escherichia coli
EXTERNAL LINKS (specific for EC-Number 3.4.21.107)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
