Information on EC 3.4.21.107 - peptidase Do

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

EC NUMBER
COMMENTARY
3.4.21.107
-
RECOMMENDED NAME
GeneOntology No.
peptidase Do
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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
show the reaction diagram
-
-
-
-
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
show the reaction diagram
the trypsin-like serine protease catalytic triad formed by His129, Asp158, and Ser240
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
-
-
cleavage of C-N-linkage
Q9LA06
-
cleavage of C-N-linkage
Escherichia coli K12
-
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
-
-
hydrolysis of peptide bond
Q9LA06
-
hydrolysis of peptide bond
Escherichia coli K12
-
-
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
bacterial PQC factor
-
-
Deg1
-
isoform
DEG2
-
isoform
DEG5
-
isoform
DEG7
-
isoform
DEG8
-
isoform
DegP
D6BU29
-
DegP
-
-
DegP
Salmonella enterica subsp. enterica serovar Typhimurium SL3261
P26982
-
-
DegP protease
-
classification of proteases
DegP protease
Escherichia coli K12
-
classification of proteases
-
DegP/HtrA
-
-
Do protease
-
-
HhoA
-
HtrA homologue A
HhoB
-
HtrA homologue B
high temperature requirement A
D6BU29
-
high temperature requirement A
-
-
high temperature requirement A protease
-
-
high temperature requirement A protease
-
-
high temperature requirement A protease
Bacillus anthracis Vollum
-
-
-
high temperature requirement A protease
-
-
high temperature requirement A protease
-
-
high temperature requirement A1
-
-
high temperature requirement factor A
-
-
high-temperature requirement A
-
-
high-temperature requirement A
-
-
high-temperature requirement A
-
-
high-temperature requirement A protease
-
-
high-temperature requirement A protease
-
-
high-temperature requirement A-1
-
-
high-temperature requirement A1
-
-
high-temperature requirement A1 protease
-
-
high-temperature requirement factor A
-
-
HtrA
Bacillus anthracis Vollum
-
-
-
HtrA
Campylobacter jejuni NCTC11168
-
-
-
HtrA
D6BU29
-
HtrA
-
classification of proteases
HtrA
Escherichia coli K12
-
-
-
HtrA
Mus musculus BALB/c
-
-
-
HtrA
Salmonella enterica subsp. enterica serovar Typhimurium SL3261
P26982
-
-
HtrA (DegP) protease
-
-
HtrA heat shock protease
-
-
HtrA protease
-
-
HtrA protease
-
-
HtrA protease
Campylobacter jejuni NCTC11168
-
-
-
HtrA protease
-
-
HtrA protease
-
-
HtrA protease
-
-
HtrA protease
-
-
HTRA serine peptidase 1
-
-
HtrA-like protease
-
-
HtrA/DegP
-
-
HtrA1
-
isoform
HtrA1
-
isoform
HtrA1
A6YFB5
-
HtrA2
-
isoform
HtrA2
-
-
HtrA3
-
-
HtrA3
-
isoform
Nma111p
-
contains an HtrA-like serine-protease domain
Omi/HtrA protease orthologue Ynm3p
-
-
protease do
-
-
-
-
protease do
-
-
protease do
-
-
PRSS11
-
-
S01.273
-
Merops ID
serine protease
-
-
serine protease HtrA
-
-
serine protease HtrA1
-
-
HTRA4
-
isoform
additional information
-
the enzyme belongs to the highly conserved family of HtrA/DegP serine proteases
additional information
-
the enzyme belongs to the highly conserved family of HtrA/DegP serine proteases
-
additional information
-
the enzyme is a member of the the HtrA/DegP family of endoserine proteases
CAS REGISTRY NUMBER
COMMENTARY
161108-11-8
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Bacillus anthracis Vollum
-
-
-
Manually annotated by BRENDA team
a member of the Burkholderia cepacia complex, strains J2315 and K56-2
-
-
Manually annotated by BRENDA team
strain NCTC11168
-
-
Manually annotated by BRENDA team
Campylobacter jejuni NCTC11168
-
-
-
Manually annotated by BRENDA team
Campylobacter jejuni NCTC11168
strain NCTC11168
-
-
Manually annotated by BRENDA team
strain TX01
UniProt
Manually annotated by BRENDA team
gene htrA
-
-
Manually annotated by BRENDA team
strain K-38 (pGP1-2)
Uniprot
Manually annotated by BRENDA team
strain K38 (pGP1-2)
-
-
Manually annotated by BRENDA team
strains DH1 and JC7623 (recBc, sbcB)
-
-
Manually annotated by BRENDA team
Escherichia coli K12
K12
-
-
Manually annotated by BRENDA team
ssp. lactis strain IL1403
SwissProt
Manually annotated by BRENDA team
strain 10403S
-
-
Manually annotated by BRENDA team
Balb/c mice
-
-
Manually annotated by BRENDA team
Mus musculus BALB/c
Balb/c mice
-
-
Manually annotated by BRENDA team
mucoid strain FRD1 and nonmucoid strain PAO1, gene mucD encoded in the algT-mucABCD operon
-
-
Manually annotated by BRENDA team
diverse strains, overview, YNM3 gene
-
-
Manually annotated by BRENDA team
DegP; strain SL3261, gene degP or htrA
SwissProt
Manually annotated by BRENDA team
Salmonella enterica subsp. enterica serovar Typhimurium SL3261
DegP; strain SL3261, gene degP or htrA
SwissProt
Manually annotated by BRENDA team
strains K7 (KCTC 13616) and UA159 (ATCC 71610)
-
-
Manually annotated by BRENDA team
strain TIGR4
-
-
Manually annotated by BRENDA team
a group A Streptococcus species, HSC5, M5 serotyp, gene htrA
-
-
Manually annotated by BRENDA team
group A streptococcus, strain HSC5
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
Bordetella pertussis lacking the periplasmic chaperone/protease DegP has a strong growth defect at 37C, and the integrity of its outer membrane is compromised
malfunction
-
HTRA1 is involved in complement regulation and amyloid deposition in age-related macular degeneration pathogenesis
malfunction
-
lack of nuclear localisation of Nma111p causes late onset of cell death during chronological ageing
malfunction
-
stable knockdown of HtrA1 in SKOV-3 and TOV-21G cells results in resistance to anoikis due to enhanced activation of epidermal growth factor receptor/AKT pathway. Downregulation of HtrA1 significantly enhances the peritoneal dissemination of SKOV-3ip1 cells in nonobese diabetic/severe combined immunodeficient mice
malfunction
-
cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy-associated mutant HTRA1 decreases protease activity and fails to decrease transforming growth factor-beta family signaling
malfunction
-
disruption of the high temperature requirement A gene affects significantly the ability of the resulting mutants to withstand heat, oxidative, ethanol and osmotic stress, exhibit delayed proliferation, and show a decrease of over six orders of magnitude in virulence as compared with the parental wild type strain
malfunction
-
HTRA1 knockout mice display reduced blood vessel in retina and upregulation of growth differentiation factor 6
malfunction
-
the loss of HTRA activity is correlated with severe diseases, including arthritis, cancer, familial ischemic cerebral smallvessel disease and age-related macular degeneration, as well as Parkinsons disease and Alzheimers disease
malfunction
Bacillus anthracis Vollum
-
disruption of the high temperature requirement A gene affects significantly the ability of the resulting mutants to withstand heat, oxidative, ethanol and osmotic stress, exhibit delayed proliferation, and show a decrease of over six orders of magnitude in virulence as compared with the parental wild type strain
-
metabolism
-
one of the targets of HtrA1 activity during fetal development is the tuberous sclerosis complex 2-tuberous sclerosis complex 1 pathway
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
D6BU29
DegP enhances the ability of TX01 to disseminate in fish blood at the advanced stage of infection, heightenes the activity of type 2 autoinducer, and increases the expression of luxS and the genes encoding components of the virulence-associated type III secretion system
physiological function
P0C0V0
DegP is a periplasmic heat-shock protein and a key component of protein quality control in the bacterial envelope. DegP along with the Skp chaperone functions to rescue outer membrane proteins that escape recognition by SurA. At temperatures below 28C, DegP is able to protect misfolded proteins from forming aggregates, whereas at temperatures above 30C, misfolded proteins are efficiently degraded by DegP
physiological function
-
DegP is critical for growth and for membrane integrity of Bordetella pertussis at 37C. The chaperone activity of DegP markedly alleviates the periplasmic stress, DegP chaperones the extended filamentous haemagglutinin polypeptide in the periplasm and is thus involved in the two-partner secretion pathway
physiological function
-
HtrA is involved in the ability of the pneumococcus to grow at high temperature, to resist oxidative stress and control the bacteriocin activity
physiological function
-
HtrA plays an important role during acid stress in Streptococcus mutans
physiological function
-
HtrA1 is a critical protease involved in proteoglycan turnover and cartilage degradation during degenerative joint disease
physiological function
-
HtrA1 is implicated in trophoblast cell migration and invasion, tumor progression, chemotherapy-induced cytotoxicity, osteoarthritis, age-related macular degeneration, and pathogenesis of Alzheimer's disease
physiological function
-
HtrA1 is involved in the inhibition of tumor growth factor-beta signaling in endometrial tissues
physiological function
-
HtrA1 modulates microtubule stability and cell motility. In vitro, purified HtrA1 promotes microtubule assembly
physiological function
-
HtrA1 protease activity is required for inhibition of epidermal growth factor receptor signaling
physiological function
-
HtrA3 plays an important role in ovarian development, granulosa cell differentiation and luteinization
physiological function
-
Nma111p functions as a nuclear serine protease that is necessary for apoptosis under cellular stress conditions, such as elevated temperature or treatment of cells with hydrogen peroxide to induce cell death. The nuclear localisation of Nma111p is required for its function in response to oxidative stress
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
physiological function
-
HtrA acts as chaperone and protease. DEG1 interacts with the reaction centre protein D2 and assists in the assembly of photosystem II
physiological function
-
HtrA displays both temperature-dependent chaperone and protease activities. The HtrA chaperone activity is sufficient for growth at high temperature or under oxidative stress (in the presence of H2O2, cumene hydroperoxide or paraquat) whereas the HtrA protease activity is essential only under conditions close to the growth limit for Campylobacter jejuni. However, the protease activity is required to prevent induction of the cytoplasmic heat shock response even under optimal growth conditions. HtrA may protect oxidatively damaged proteins
physiological function
-
HtrA is a major virulence determinant of Bacillus anthracis
physiological function
-
HtrA is a secreted virulence factor from Helicobacter pylori, which cleaves the ectodomain of E-cadherin. the E-cadherin shedding disrupts epithelial barrier functions allowing Helicobacter pylori to access the intercellular space
physiological function
-
HtrA is important for the biogenesis of extracellular proteins and thus for biofilm formation
physiological function
-
HtrA, HhoA and HhoB are important for survival of Synechocystis sp. strain PCC 6803 under high light and temperature stresses. The three proteases may act as protein-quality-control factors degrading denatured and damaged proteins
physiological function
-
HTRA1 decreases transforming growth factor-beta1 signaling triggered by pro-transforming growth factor-beta1 in the intracellular space
physiological function
-
HTRA1 plays a critical role in the regulation of angiogenesis via transforming growth factor-beta signaling
physiological function
-
isoform HTRA1 regulates cell proliferation by sequestering or proteolysing transforming growth factor-beta and bone morphogenetic protein, proteins of the transforming growth factor family, and IGF-binding protein 5 in the extracellular matrix. Isoform HTRA2 affects quality control in the intermembrane space of mitochondria. HTRA1 and HTRA2 are implicated in tumor suppression and in the control of proliferation, migration and neurodegeneration. Isoform HTRA3 is implicated in pregnancy, and endometrial and ovarian cancers55
physiological function
Bacillus anthracis Vollum
-
HtrA is a major virulence determinant of Bacillus anthracis
-
physiological function
Campylobacter jejuni NCTC11168
-
HtrA displays both temperature-dependent chaperone and protease activities. The HtrA chaperone activity is sufficient for growth at high temperature or under oxidative stress (in the presence of H2O2, cumene hydroperoxide or paraquat) whereas the HtrA protease activity is essential only under conditions close to the growth limit for Campylobacter jejuni. However, the protease activity is required to prevent induction of the cytoplasmic heat shock response even under optimal growth conditions. HtrA may protect oxidatively damaged proteins
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ADAM9 + H2O
?
show the reaction diagram
-
54% cleavage
-
-
?
aggrecan + H2O
aggrecan fragments
show the reaction diagram
-
the HtrA1-specific cleavage site is VQTV3562357TWPD within the interglobular domain of aggrecan
-
-
?
alpha-casein + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-casein + H2O
?
show the reaction diagram
-
weaker substrate than beta-casein
-
?
alpha-lactalbumin + H2O
?
show the reaction diagram
-
-
-
?
alpha-lactalbumin + H2O
?
show the reaction diagram
-
acts on the fully unfolded protein but not on the native form
-
?
alpha-lactalbumin + H2O
?
show the reaction diagram
-
only when incubated in the presence of 20 mM dithiothreitol, which reduces the structural disulfide bonds and unfold the protein, and above 34C, is CtHtrA able to proteolyse alpha-lactalbumin
-
-
?
alpha-Tubulin + H2O
?
show the reaction diagram
-
-
-
-
?
alpha2-macroglobulin + H2O
?
show the reaction diagram
-
55% cleavage
-
-
?
amylase MalS + H2O
?
show the reaction diagram
-
-
-
?
Arc repressor + H2O
?
show the reaction diagram
-
-
-
?
autolysin AcmA + H2O
?
show the reaction diagram
Q9LA06
-
-
?
azocasein + H2O
?
show the reaction diagram
D6BU29
-
-
-
?
beta-casein + H2O
?
show the reaction diagram
-
-
-
?
beta-casein + H2O
?
show the reaction diagram
-
-
-
?
beta-casein + H2O
?
show the reaction diagram
-
-
-
?
beta-casein + H2O
?
show the reaction diagram
-
-
-
?
beta-casein + H2O
?
show the reaction diagram
-
-
-
?
beta-casein + H2O
?
show the reaction diagram
-
-
-
?
beta-casein + H2O
?
show the reaction diagram
-
-
-
-
?
beta-casein + H2O
?
show the reaction diagram
P0C0V0
-
-
-
?
beta-casein + H2O
?
show the reaction diagram
-
-
-
-
?
beta-casein + H2O
?
show the reaction diagram
-
-
-
-
?
beta-casein + H2O
?
show the reaction diagram
-
-
-
-
?
beta-casein + H2O
?
show the reaction diagram
-
-
-
-
?
beta-casein + H2O
?
show the reaction diagram
-
better substrate than alpha-casein
-
?
beta-casein + H2O
?
show the reaction diagram
-
cleaves beta-casein yielding several polypeptide fragments
-
?
beta-casein + H2O
?
show the reaction diagram
-
nonphysiological substrate of DegP
-
-
?
beta-casein + H2O
?
show the reaction diagram
-
little uncleaved beta-casein remains in assays with recombinant HtrA, and a prominent degradation fragment appears. Recombinant HhoA completely degrades the excess of beta-casein, whereas recombinant HhoB shows only little activity and generates a prominent degradation fragment with a slightly lower molecular mass than intact beta-casein. The C-terminal cleavage sites Val162, Gln141 and Val130 are identified for recombinant HtrA. A common cleavage site at Leu165 is found for HhoA and HhoB, however, HhoA additionally cleaves beta-casein at Ala101 generating two proteolytic fragments, the N-terminal 1-101 as well as the C-terminal 102-199 amino acid fragments
-
-
?
beta-casein + H2O
?
show the reaction diagram
Campylobacter jejuni NCTC11168
-
-
-
-
?
beta-casein + H2O
beta-casein peptide fragments
show the reaction diagram
-
-
-
-
?
beta-casein + H2O
beta-casein peptide fragments
show the reaction diagram
-
the cleavage activity at 37C is ATP independent, not significantly influenced by buffer composition, active over a broad range of pH, and with a broad optimum at pH 6.5, and 20 mM salts, e.g. magnesium sulfate, magnesium chloride, or sodium chloride, improving activity, determination of cleavage sites
-
-
?
beta-tubulin + H2O
?
show the reaction diagram
-
-
-
-
?
biglycan + H2O
?
show the reaction diagram
-
-
-
-
?
biglycan + H2O
?
show the reaction diagram
A6YFB5
-
-
-
?
biglycan + H2O
?
show the reaction diagram
-
substrate of isoforms HTRA1 and HTRA3
-
-
?
BODIPY TR-X casein + H2O
?
show the reaction diagram
-
-
-
-
?
bone morphogenetic protein + H2O
?
show the reaction diagram
-
substrate of isoform HTRA1
-
-
?
Bovine serum albumin + H2O
?
show the reaction diagram
-
denatured
-
?
casein + H2O
?
show the reaction diagram
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
major pilin subunit of the Pap pilus
-
?
casein + H2O
?
show the reaction diagram
-
partially unfolded casein
-
?
chloride intracellular channel protein 1 + H2O
?
show the reaction diagram
-
51% cleavage
-
-
?
citrate synthase + H2O
?
show the reaction diagram
-
acts on the thermally unfolded synthase but not on the native form
-
?
clusterin + H2O
?
show the reaction diagram
-
50% cleavage
-
-
?
colicin A lysis protein + H2O
?
show the reaction diagram
Escherichia coli, Escherichia coli K12
-
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
-
?
colicin A lysis protein precursor + H2O
?
show the reaction diagram
-
-
-
?
D1 protein + H2O
?
show the reaction diagram
-
degrades photodamaged D1 protein of photosystem II
-
?
decorin + H2O
?
show the reaction diagram
-
substrate of isoforms HTRA1 and HTRA3
-
-
?
decorin + H2O
decorin peptide fragments
show the reaction diagram
-
the small leucine-rich proteoglycan is highly expressed in bone and regulates type I collagen fibril assembly
generation of fragments ranging from 150 to 75 kDa
-
?
decorin + H2O
decorin peptide fragments
show the reaction diagram
-
a small leucine-rich proteoglycan
-
-
?
decorin + H2O
decorin peptide fragments
show the reaction diagram
-
a small leucine-rich proteoglycan, human substrate
generation of fragments ranging from 150 to 75 kDa
-
?
DPMFKLV-4-nitroanilide + H2O
DPMFKLV + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
E-cadherin + H2O
?
show the reaction diagram
-
-
-
-
?
E-cadherin + H2O
85 kDa N-terminal fragment + 40 kDa C-terminal fragment
show the reaction diagram
-
selective substrate
-
-
?
Faa1p + H2O
?
show the reaction diagram
-
direct interaction of Faa1p with the Omi/HtrA protease orthologue Ynm3p alters lipid homeostasis, Ynm3p modulates fatty acid metabolism and gene regulation through negative regulation of ACSL activity, overview
-
-
?
fascin + H2O
?
show the reaction diagram
-
40% cleavage
-
-
?
fibromodulin + H2O
?
show the reaction diagram
-
90% cleavage
-
-
?
Fibronectin + H2O
?
show the reaction diagram
-
-
-
-
?
Fibronectin + H2O
?
show the reaction diagram
-
selective substrate
-
-
?
Fibronectin + H2O
?
show the reaction diagram
-
substrate of isoform HTRA1
-
-
?
fibronectin + H2O
fibronectin peptide fragments
show the reaction diagram
-
-
-
-
?
fibronectin + H2O
fibronectin peptide fragments
show the reaction diagram
-
a major noncollagenous component of mineralized bone matrix
generation of fragments ranging from 200 to 150 kDa
-
?
fibronectin + H2O
fibronectin peptide fragments
show the reaction diagram
-
HtrA is involved in cartilage catabolism
-
-
?
fibronectin + H2O
fibronectin peptide fragments
show the reaction diagram
-
human plasma-derived substrate
generation of fragments ranging from 200 to 150 kDa
-
?
filamentous haemagglutinin precursor + H2O
?
show the reaction diagram
-
DegP contributes to degrading the filamentous haemagglutinin precursor when it is blocked intracellularly
-
-
?
gamma-tubulin + H2O
?
show the reaction diagram
-
-
-
-
?
Globin + H2O
?
show the reaction diagram
-
-
-
?
glypican-4 + H2O
?
show the reaction diagram
A6YFB5
-
-
-
?
HCLS1-associated X1 + H2O
?
show the reaction diagram
-
substrate of isoform HTRA2
-
-
?
HYTAVVKKSSAV + H2O
?
show the reaction diagram
-
model substrate
-
?
IciA protein + H2O
?
show the reaction diagram
-
inhibitor of DNA replication initiation
-
?
insulin beta-chain + H2O
?
show the reaction diagram
-
-
-
-
?
insulin beta-chain + H2O
?
show the reaction diagram
-
oxidized beta-chain which is fully unfolded
-
?
insulin growth factor-binding protein 5 + H2O
?
show the reaction diagram
-
substrate of isoform HTRA1
-
-
?
LamB + H2O
?
show the reaction diagram
-
DegP functions as a geniune chaperone
-
-
?
lambda repressor + H2O
?
show the reaction diagram
-
N-terminal domain
-
?
lysozmye + H2O
?
show the reaction diagram
-
-
-
-
?
Lysozyme + H2O
?
show the reaction diagram
-
can only be digested in the presence of reducing agents
-
?
malate dehydrogenase + H2O
?
show the reaction diagram
-
-
-
-
?
malate dehydrogenase + H2O
?
show the reaction diagram
-
acts on the thermally unfolded protein but not on the native form
-
?
outer membrane protein + H2O
?
show the reaction diagram
P0C0V0
-
-
-
?
outer membrane protein A + H2O
?
show the reaction diagram
-
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
?
show the reaction diagram
-
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
?
show the reaction diagram
-
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
-
-
?
PapA + H2O
?
show the reaction diagram
-
major pilin subunit of the Pap pilus
-
?
PMMGKASPV-4-nitroanilide + H2O
PMMGKASPV + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
pro-transforming growth factor-beta1 + H2O
mature transforming growth factor-beta1 + latency-associated peptide
show the reaction diagram
-
-
latency-associated peptide is the N-terminal of pro-transforming growth factor-beta1
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
P0C0V0
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
Q9LA06
-
-
?
Protein + H2O
?
show the reaction diagram
-
cleaves between paired valine residues
-
?
Protein + H2O
?
show the reaction diagram
-
cleaves model substrates at discrete Val/Xaa or Ile/Xaa sites
-
?
Protein + H2O
?
show the reaction diagram
-
cleaves preferably at hydrophobic side chains at the P1 position
-
?
Protein + H2O
?
show the reaction diagram
-
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
?
show the reaction diagram
-
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
?
show the reaction diagram
-
enzyme recognizes an ssrA-encoded peptide tag which is tagged to misfolded proteins or protein fragments
-
?
Protein + H2O
?
show the reaction diagram
Escherichia coli K12
-
-
-
?
PVFNTLPMMGKASPV-4-nitroanilide + H2O
PVFNTLPMMGKASPV + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
reaction centre protein D1 + H2O
?
show the reaction diagram
-
substrate of isoform DEG1
-
-
?
reaction centre protein D2 + H2O
?
show the reaction diagram
-
substrate of isoforms DEG1, DEG5, DEG7 and DEG8
-
-
?
reduced alkaline phosphatase + H2O
?
show the reaction diagram
-
-
-
-
?
RseA + H2O
?
show the reaction diagram
-
physiological substrate of DegP
-
-
?
SPMFKGV-4-nitroanilide + H2O
SPMFKGV + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
Staphylococcus aureus nuclease Nuc precursor + H2O
?
show the reaction diagram
Q9LA06
-
-
?
syndecan-4 + H2O
?
show the reaction diagram
A6YFB5
-
-
-
?
talin-1 + H2O
?
show the reaction diagram
-
21% cleavage
-
-
?
transforming growth factor-beta + H2O
?
show the reaction diagram
-
substrate of isoform HTRA1
-
-
?
tuberous sclerosis complex 2 protein + H2O
?
show the reaction diagram
-
specific substrate for HtrA1 which is cleaved both in vitro and in vivo
-
-
?
VFNTLPMMGKASPV-4-nitroanilide + H2O
VFNTLPMMGKASPV + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
Vitronectin + H2O
?
show the reaction diagram
-
54% cleavage
-
-
?
matrix Gla protein + H2O
processed matrix Gla protein + 12 kDa peptide
show the reaction diagram
-
the protein substrate is present in cartilage, bone, and arteries, cleavage of MGP at the C terminus
-
-
?
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
?
-
-
deletion mutant is unable to grow at an elevated temperature and to survive within macrophages after phagocytosis
-
?
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
?
-
P0C0V0
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, acts as protease, chaperone and regulator of apoptosis
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, chaperone and proteolytic activity
-
?
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 42C
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, enzyme is indispensable for bacterial survival at temperatures above 42C
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, involved in arthritis, cell growth, stress response, apoptosis and aging, possible tumor suppressor function
-
?
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
?
-
-
mutants are deficient in their ability to survive in mice or macrophages
-
?
additional information
?
-
Q9LA06
role in extracellular proteolysis, proteolysis occurs during or after export to the cell surface, involved in the degradation of abnormal exported 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
?
-
-
DegP degrades unfolded or misfolded, secreted, and accumulated inactive proteins and is important for cell survival, especially in the absence of DsbA
-
-
-
additional information
?
-
-
HtrA inhibits the unfolded lysozyme substrate aggregation over the range of temperatures at 30-45C, 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 is essential for the maturation of cysteine protease streptococcal pyrogenic exotoxin B, SpeB, but is unable to directly process SpeB zymogen, proSpeB to the active form in vitro, thus playing an indirect role in the maturation, overview
-
-
-
additional information
?
-
-
HtrA is involved in the stress response of several important Gram-negative, as well as gram-positive, pathogens, HtrA is required for efficient Listeria monocytogenes biofilm formation at high temperatures
-
-
-
additional information
?
-
-
HtrA is specific for mature mucosal mast cells
-
-
-
additional information
?
-
-
HtrA1 degrades specific matrix-associated proteins, HtrA1 inhibits mineral deposition by osteoblasts, the protease domain and the PDZ domain are essential for the inhibition of osteoblast mineralization by HtrA1, overview
-
-
-
additional information
?
-
-
HtrA1 expression is regulated by cisplatin and paclitaxel, and upregulation results in catalytic activation of HtrA1, overview, HtrA1 influences tumor response to chemotherapy by modulating hemotherapy-induced cytotoxicity, HtrA1 in ovarian and gastric cancers may contribute to in vivo chemoresistance, overview
-
-
-
additional information
?
-
-
HtrA1 plays a role in arthritic disease, within the context of arthritis pathology HtrA1 contributes to cartilage degradation, overview
-
-
-
additional information
?
-
A6YFB5
HtrA1 promotes posterior development in mRNA-injected Xenopus laevis embryos, e.g. induces secondary tail-like structures, expansion of mesoderm, and formation of ectopic neurons in an FGF-dependent manner, HtrA1 activates FGF/ERK signaling and the transcription of FGF genes by cleaving proteoglycans and releasing cell surface-bound FGF ligands, overview
-
-
-
additional information
?
-
-
MucD negatively regulates alginate production on genetic level, MucD-deficient strain show temperature-dependent alginate production, while MucD-containing strains do not, which is independent of MucD proteolytic activity, overview
-
-
-
additional information
?
-
P26982
the enzyme is involved in survival of the bacteria under heat shock stress conditions in vitro and in vivo, overview
-
-
-
additional information
?
-
-
the enzyme plays a role in the Burkholderia cenocepacia stress response, HtrABCAL2829 is required for growth of Burkholderia cenocepacia upon exposure to osmotic stress by NaCl or KCl, and thermal stress at 44C
-
-
-
additional information
?
-
-
HtrA sequence specificity, overview, no activity with albumin and myoglobin at 37C, HtrA acts as both a chaperone and protease, HtrA mutant S247A is able to chaperone insulin B-chain, irrespective of temperature, but at 30C only HtrA and not mutant S247A displays significant chaperone activity for alpha-lactalbumin, overview
-
-
-
additional information
?
-
-
HtrA shows chaperone-like activity, overview
-
-
-
additional information
?
-
-
HtrA1 is a secreted multidomain protein with serine protease activity
-
-
-
additional information
?
-
-
HTRA1 does not cleave CFH protein, complement component C3 and complement component C3b
-
-
-
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
?
-
-
HTRA1 interacts with presenilin 1 to cleave one product of gamma-secretase
-
-
-
additional information
?
-
-
HTRA1 fails to cleave mature transforming growth factor-beta1
-
-
-
additional information
?
-
-
HtrA1 shows no activity towards tuberous sclerosis complex 1 protein and bovine serum albumin
-
-
-
additional information
?
-
-
no activity with correctly folded globular bovine serum albumin or lysozyme
-
-
-
additional information
?
-
-
the enzyme does not cleave recombinant immunoglobulin A, epidermal growth factor receptor or junctional adhesion molecule
-
-
-
additional information
?
-
-
HtrA is involved in the stress response of several important Gram-negative, as well as gram-positive, pathogens, HtrA is required for efficient Listeria monocytogenes biofilm formation at high temperatures
-
-
-
additional information
?
-
Mus musculus BALB/c
-
HtrA is specific for mature mucosal mast cells
-
-
-
additional information
?
-
Escherichia coli K12
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
Salmonella enterica subsp. enterica serovar Typhimurium SL3261
P26982
the enzyme is involved in survival of the bacteria under heat shock stress conditions in vitro and in vivo, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ADAM9 + H2O
?
show the reaction diagram
-
54% cleavage
-
-
?
aggrecan + H2O
aggrecan fragments
show the reaction diagram
-
the HtrA1-specific cleavage site is VQTV3562357TWPD within the interglobular domain of aggrecan
-
-
?
alpha-Tubulin + H2O
?
show the reaction diagram
-
-
-
-
?
alpha2-macroglobulin + H2O
?
show the reaction diagram
-
55% cleavage
-
-
?
beta-tubulin + H2O
?
show the reaction diagram
-
-
-
-
?
biglycan + H2O
?
show the reaction diagram
-
substrate of isoforms HTRA1 and HTRA3
-
-
?
bone morphogenetic protein + H2O
?
show the reaction diagram
-
substrate of isoform HTRA1
-
-
?
chloride intracellular channel protein 1 + H2O
?
show the reaction diagram
-
51% cleavage
-
-
?
clusterin + H2O
?
show the reaction diagram
-
50% cleavage
-
-
?
decorin + H2O
?
show the reaction diagram
-
substrate of isoforms HTRA1 and HTRA3
-
-
?
decorin + H2O
decorin peptide fragments
show the reaction diagram
-
the small leucine-rich proteoglycan is highly expressed in bone and regulates type I collagen fibril assembly
generation of fragments ranging from 150 to 75 kDa
-
?
E-cadherin + H2O
?
show the reaction diagram
-
-
-
-
?
E-cadherin + H2O
85 kDa N-terminal fragment + 40 kDa C-terminal fragment
show the reaction diagram
-
selective substrate
-
-
?
Faa1p + H2O
?
show the reaction diagram
-
direct interaction of Faa1p with the Omi/HtrA protease orthologue Ynm3p alters lipid homeostasis, Ynm3p modulates fatty acid metabolism and gene regulation through negative regulation of ACSL activity, overview
-
-
?
fascin + H2O
?
show the reaction diagram
-
40% cleavage
-
-
?
fibromodulin + H2O
?
show the reaction diagram
-
90% cleavage
-
-
?
Fibronectin + H2O
?
show the reaction diagram
-
selective substrate
-
-
?
Fibronectin + H2O
?
show the reaction diagram
-
substrate of isoform HTRA1
-
-
?
fibronectin + H2O
fibronectin peptide fragments
show the reaction diagram
-
a major noncollagenous component of mineralized bone matrix
generation of fragments ranging from 200 to 150 kDa
-
?
fibronectin + H2O
fibronectin peptide fragments
show the reaction diagram
-
HtrA is involved in cartilage catabolism
-
-
?
filamentous haemagglutinin precursor + H2O
?
show the reaction diagram
-
DegP contributes to degrading the filamentous haemagglutinin precursor when it is blocked intracellularly
-
-
?
gamma-tubulin + H2O
?
show the reaction diagram
-
-
-
-
?
HCLS1-associated X1 + H2O
?
show the reaction diagram
-
substrate of isoform HTRA2
-
-
?
insulin beta-chain + H2O
?
show the reaction diagram
-
-
-
-
?
insulin growth factor-binding protein 5 + H2O
?
show the reaction diagram
-
substrate of isoform HTRA1
-
-
?
LamB + H2O
?
show the reaction diagram
-
DegP functions as a geniune chaperone
-
-
?
outer membrane protein + H2O
?
show the reaction diagram
P0C0V0
-
-
-
?
outer membrane protein A + H2O
?
show the reaction diagram
-
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
?
show the reaction diagram
-
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
?
show the reaction diagram
-
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
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
P0C0V0
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
-
-
-
?
Protein + H2O
?
show the reaction diagram
Q9LA06
-
-
?
Protein + H2O
?
show the reaction diagram
Escherichia coli K12
-
-
-
?
reaction centre protein D1 + H2O
?
show the reaction diagram
-
substrate of isoform DEG1
-
-
?
reaction centre protein D2 + H2O
?
show the reaction diagram
-
substrate of isoforms DEG1, DEG5, DEG7 and DEG8
-
-
?
talin-1 + H2O
?
show the reaction diagram
-
21% cleavage
-
-
?
transforming growth factor-beta + H2O
?
show the reaction diagram
-
substrate of isoform HTRA1
-
-
?
tuberous sclerosis complex 2 protein + H2O
?
show the reaction diagram
-
specific substrate for HtrA1 which is cleaved both in vitro and in vivo
-
-
?
Vitronectin + H2O
?
show the reaction diagram
-
54% cleavage
-
-
?
matrix Gla protein + H2O
processed matrix Gla protein + 12 kDa peptide
show the reaction diagram
-
the protein substrate is present in cartilage, bone, and arteries
-
-
?
additional information
?
-
-
deletion mutant is unable to grow at an elevated temperature and to survive within macrophages after phagocytosis
-
?
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
?
-
P0C0V0
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, acts as protease, chaperone and regulator of apoptosis
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, chaperone and proteolytic activity
-
?
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 42C
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, enzyme is indispensable for bacterial survival at temperatures above 42C
-
?
additional information
?
-
-
involved in the degradation of damaged proteins, involved in arthritis, cell growth, stress response, apoptosis and aging, possible tumor suppressor function
-
?
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
?
-
-
mutants are deficient in their ability to survive in mice or macrophages
-
?
additional information
?
-
Q9LA06
role in extracellular proteolysis, proteolysis occurs during or after export to the cell surface, involved in the degradation of abnormal exported proteins
-
?
additional information
?
-
-
allosteric activation of DegP by stress signals during bacterial protein quality control, regulation mechanism, pathway scheme, overview
-
-
-
additional information
?
-
-
DegP degrades unfolded or misfolded, secreted, and accumulated inactive proteins and is important for cell survival, especially in the absence of DsbA
-
-
-
additional information
?
-
-
HtrA inhibits the unfolded lysozyme substrate aggregation over the range of temperatures at 30-45C, 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 is essential for the maturation of cysteine protease streptococcal pyrogenic exotoxin B, SpeB, but is unable to directly process SpeB zymogen, proSpeB to the active form in vitro, thus playing an indirect role in the maturation, overview
-
-
-
additional information
?
-
-
HtrA is involved in the stress response of several important Gram-negative, as well as gram-positive, pathogens, HtrA is required for efficient Listeria monocytogenes biofilm formation at high temperatures
-
-
-
additional information
?
-
-
HtrA is specific for mature mucosal mast cells
-
-
-
additional information
?
-
-
HtrA1 degrades specific matrix-associated proteins, HtrA1 inhibits mineral deposition by osteoblasts, the protease domain and the PDZ domain are essential for the inhibition of osteoblast mineralization by HtrA1, overview
-
-
-
additional information
?
-
-
HtrA1 expression is regulated by cisplatin and paclitaxel, and upregulation results in catalytic activation of HtrA1, overview, HtrA1 influences tumor response to chemotherapy by modulating hemotherapy-induced cytotoxicity, HtrA1 in ovarian and gastric cancers may contribute to in vivo chemoresistance, overview
-
-
-
additional information
?
-
-
HtrA1 plays a role in arthritic disease, within the context of arthritis pathology HtrA1 contributes to cartilage degradation, overview
-
-
-
additional information
?
-
A6YFB5
HtrA1 promotes posterior development in mRNA-injected Xenopus laevis embryos, e.g. induces secondary tail-like structures, expansion of mesoderm, and formation of ectopic neurons in an FGF-dependent manner, HtrA1 activates FGF/ERK signaling and the transcription of FGF genes by cleaving proteoglycans and releasing cell surface-bound FGF ligands, overview
-
-
-
additional information
?
-
-
MucD negatively regulates alginate production on genetic level, MucD-deficient strain show temperature-dependent alginate production, while MucD-containing strains do not, which is independent of MucD proteolytic activity, overview
-
-
-
additional information
?
-
P26982
the enzyme is involved in survival of the bacteria under heat shock stress conditions in vitro and in vivo, overview
-
-
-
additional information
?
-
-
the enzyme plays a role in the Burkholderia cenocepacia stress response, HtrABCAL2829 is required for growth of Burkholderia cenocepacia upon exposure to osmotic stress by NaCl or KCl, and thermal stress at 44C
-
-
-
additional information
?
-
-
HTRA1 does not cleave CFH protein, complement component C3 and complement component C3b
-
-
-
additional information
?
-
-
when unfolded proteins bind to CpxP, DegP efficiently degrades this protein complex
-
-
-
additional information
?
-
-
HTRA1 interacts with presenilin 1 to cleave one product of gamma-secretase
-
-
-
additional information
?
-
-
HtrA is involved in the stress response of several important Gram-negative, as well as gram-positive, pathogens, HtrA is required for efficient Listeria monocytogenes biofilm formation at high temperatures
-
-
-
additional information
?
-
Mus musculus BALB/c
-
HtrA is specific for mature mucosal mast cells
-
-
-
additional information
?
-
Escherichia coli K12
-
involved in the degradation of damaged proteins
-
?
additional information
?
-
Salmonella enterica subsp. enterica serovar Typhimurium SL3261
P26982
the enzyme is involved in survival of the bacteria under heat shock stress conditions in vitro and in vivo, overview
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
largely indpependent of cofactors such as ATP
-
additional information
-
ATP is not required
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
the activity of recombinant HtrA and HhoA increases almost 4-6fold in the presence of 5 mM CaCl2 and remains constant at higher concentrations. The activity of recombinant HhoB increases more gradually up to 14fold, reaching the maximal level at 10 mM CaCl2. Almost no proteolytic activity is detected for recombinant HhoB in the absence of Ca2+
CaCl2
-
stimulates at 5 mM
Mg2+
-
stimulates at 10 mM
Mg2+
-
the activity of recombinant HtrA and HhoA increases almost 4-6fold in the presence of 5 mM MgCl2 and remains constant at higher concentrations. The activity of recombinant HhoB increases more gradually up to 14fold, reaching the maximal level at 10 mM MgCl2
MgCl2
-
stimulates at 5 mM
MgCl2
-
activates at 20 mM
MgSO4
-
activates at 20 mM
NaCl
-
activates at 20 mM
NaCl
-
activates
MnCl2
-
stimulates at 5 mM
additional information
-
largely independent of divalent cations
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
AEBSF
-
-
cardiolipin
-
-
diisopropyl fluorophosphate
-
binds covalently to the enzyme
diisopropyl fluorophosphates
-
-
diisopropylfluorophosphate
-
efficient inhibitor
diisopropylfluorophosphate
-
-
DnaJ
-
chaperone protein
-
EDTA
-
inhibits at 10 mM
HpHtrA inhibitor
-
small-molecule inhibitor that completely blocks E-cadherin cleavage by HtrA at 0.03 mM
-
phosphatidylglycerol
-
inhibits activity at 50-55C
PMMGKASPV-chloromethylketone
-
49% residual activity at 0.5 mM
PVFNTLPMMGKASPV-chloromethylketone
-
63% residual activity at 0.5 mM
SPMFKGV-chloromethylketone
-
3% residual activity at 0.5 mM
VFNTLPMMGKASPV-chloromethylketone
-
57% residual activity at 0.5 mM
HtrA1 inhibitor
-
-
-
additional information
-
wild type and HtrA mutant are not sensitive to H2O2, cumene hydroperoxide and paraquat, moreover the wild type is not sensitive to oxygen while the mutant has a reduced oxygen tolerance
-
additional information
-
rHtrA-mediated decline in transformation efficiency can not be corrected with excess competence-stimulating peptide
-
additional information
-
no inhibition by aprotinin and trypsin inhibitor
-
additional information
-
no inhibition by Z-VAD-FMK, a broad-spectrum caspase inhibitor, nor dominant-negative caspase 9
-
additional information
-
not inhibited by SGRVVPGYGHA-chloromethylketone and IWNTLNSGRVVPGTGHA-chloromethylketone
-
additional information
-
not inhibited by benzyloxycarbonyl-VAD-fluoromethylketone
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
15 residue presenilin-1 peptide
-
activation
-
cardiolipin
P0C0V0
enhances DegP proteolytic activity at high temperatures
CPII
-
cleavage of aggrecan by HtrA1 is strongly enhanced by HtrA1 agonists such as CPII, a C-terminal hexapeptide derived from the C-propeptide of procollagen IIalpha1
-
dermatan sulfate
A6YFB5
triggers HtrA1-induced peteriorization, overview
DKVLVVWAGQQ
-
MalS-derived peptide sequence
DNRNGNVYDF
-
-
DNRNGNVYFF
-
thermodynamic binding affinities of the peptide
DNRNGNVYGF
-
-
DNRNGNVYIF
-
-
DNRNGNVYKF
-
-
DNRNGNVYLF
-
thermodynamic binding affinities of the peptide
DNRNGNVYQF
-
-
DNRNGNVYSF
-
-
DNRNGNVYWF
-
-
DNRNGNVYYF
-
-
DTT
-
only when incubated in the presence of 20 mM dithiothreitol, which reduces the structural disulfide bonds and unfold the protein, and above 34C, is CtHtrA able to proteolyse alpha-lactalbumin
Heparan sulfate
A6YFB5
triggers HtrA1-induced peteriorization, overview
OMP C-terminal tripeptide YYF-COOH
-
activation less efficient as compared to 15 residue presenilin-1 peptide
phosphatidyl glycerol
P0C0V0
enhances DegP proteolytic activity at high temperatures
phosphatidylglycerol
-
activates at 37-45C
puromycin
-
increases level of misfolded proteins, HtrA is required for growth under conditions in which misfolded proteins accumulate
YTMKAAGLGK
-
PhoA-derived peptide sequence
IVALGLVYQF
-
OmpC-derived peptide sequence
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
-
no activation by 3 residue presenelin-1 peptide
-
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
-
additional information
A6YFB5
HtrA1 is expressed in early embryo and activated by FGF signals
-
additional information
-
both cisplatin and paclitaxel treatment upregulates HtrA1 expression resulting in limited autoproteolysis and activation of HtrA1, active HtrA1 induces cell death in a serine protease-dependent manner and activates caspase-3/7 activity, overview
-
additional information
P26982
DegP and DegQ are constitutive, while DegS needs to be activated by an extracellular signal
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00021
HtrA1 inhibitor
-
pH 8.5, 37C, recombinant enzyme
-
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
-
using PVFNTLPMMGKASPV-4-nitroanilide as substrate, in 50 mM NaH2PO4, pH 8.0, temperature not specified in the publication; using SPMFKGV-4-nitroanilide as substrate, in 50 mM NaH2PO4, pH 8.0, temperature not specified in the publication
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
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5 - 6
-
HtrA in the absence of Ca2+
5.5 - 6.5
-
HhoB activity shows an optimum at pH 5.5-6.5 in the presence of 10 mM Ca2+
6.5
-
broad optimum
6.5
-
HhoA in the absence of Ca2+
7
-
HtrA in the presence of 10 mM Ca2+
7.6
-
protease assay
8
-
activation assay at
8
-
assay at
8
-
assay at
8
-
HhoA activity shows an optimum at pH 8.0 or higher in the presence of 10 mM Ca2+
8.5
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.8 - 10
-
proteolytic activity is largely independent of the pH
6 - 9
D6BU29
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20
-
reduced alkaline phosphatase is efficiently degraded at 20C, both in vivo and in vitro. The cleavage is most efficient in the case of a C57A/C69A mutant, lacking its internal SS bond
37
-
assay at, chaperone and protease activities
37
-
assay at
37
-
assay at
42
-
substrate-binding using mutant S210A and protease assay
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20 - 30
-
almost no activity below 20C, activity rapidly increases above 30C
30 - 42
-
enzyme activity is constant within this temperature range
34 - 55
-
low activity below 34C, rapid loss of activity at 55C
37 - 44
-
the HtrA mutant forms colonies with the same frequency as the wild type at 37C and 42C, the ability of the mutant to form colonies at 44C was greatly reduced as compared to the wild type
37 - 45
-
enzyme is more efficient at 45C than at 37C
37 - 45
-
no change of cell density of wild type, cell density of the mutant rapidly falls, protease Do essential for the cells survival at high temperatures
37 - 55
-
activity rapidly increases with temperature
40 - 50
D6BU29
-
44
-
at 44 C function of DegP in mutant strain CLC198 can be complemented by HtrA2
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
primary chondrocyte
Manually annotated by BRENDA team
-
alternative splice form lacing exons 3 and 7
Manually annotated by BRENDA team
-
high level of enzyme expression in decidua capsularis specifically at the decidual-trophoblast interface where active involution occurs
Manually annotated by BRENDA team
A6YFB5
HtrA1 is expressed in early embryo and activated by FGF signals
Manually annotated by BRENDA team
-
synovial, main source of secreted enzyme
Manually annotated by BRENDA team
-
high HtrA1 expression levels
Manually annotated by BRENDA team
-
the luteinizing granulosa cells of the corpus luteum express the highest levels of Htra3
Manually annotated by BRENDA team
-
alternative splice form lacing exons 3 and 7
Manually annotated by BRENDA team
-
from cord blood, expression and enzyme content analysis, the enzyme is constitutively released from mast cells, overview
Manually annotated by BRENDA team
-
peritoneal, mucosal, and connective tissue-derived mast cells, the enzyme expression is highly up-regulated during mucosal mast cell differentiation, enzyme levels in mucosal mast cells are much higher compared to connective-tissue-type mast cells, expression and enzyme content analysis, overview
Manually annotated by BRENDA team
Mus musculus BALB/c
-
peritoneal, mucosal, and connective tissue-derived mast cells, the enzyme expression is highly up-regulated during mucosal mast cell differentiation, enzyme levels in mucosal mast cells are much higher compared to connective-tissue-type mast cells, expression and enzyme content analysis, overview
-
Manually annotated by BRENDA team
-
low endogenous HtrA1 level
Manually annotated by BRENDA team
-
high HtrA1 expression levels
Manually annotated by BRENDA team
-
first and third trimester (5-14 weeks and 28-40 weeks respectively)
Manually annotated by BRENDA team
-
elevated synovial HtrA1 levels in fluids obtained from rheumatoid and osteoarthritis patients
Manually annotated by BRENDA team
-
alternative splice form lacing exons 3 and 7
Manually annotated by BRENDA team
-
HtrA1 especially expressed in giant cells during the early stages of placental development
Manually annotated by BRENDA team
additional information
-
HtrA expression can be lowered by the suppression of the acid tolerance response (ATR)
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
intracellular HtrA1 associates with centrosomes
Manually annotated by BRENDA team
-
especially close to microvilli that characterizes the plasma membrane of syncytiotrophoblast cells, or in the extracytoplasmic space of the stroma of placental villi between the collagen fibers and on collagen fibers themselves
Manually annotated by BRENDA team
-
constitutive secretion from mast cells unaffected by degranulating compounds
-
Manually annotated by BRENDA team
A6YFB5
secretion of embryo HtrA1
-
Manually annotated by BRENDA team
-
periplasmatic side of the membrane
-
Manually annotated by BRENDA team
-
periplasmic side of the inner membrane
-
Manually annotated by BRENDA team
-
bowl-shaped DegP assemblies on membranes have higher proteolytic activity but lower chaperone-Like activity
Manually annotated by BRENDA team
-
HtrA1 is localized to microtubules in both interphase and mitotic cells
Manually annotated by BRENDA team
-
intracellular HtrA1 associates with newly polymerized microtubules
Manually annotated by BRENDA team
-
Nma111p does not shuttle between the nucleus and cytoplasm
Manually annotated by BRENDA team
-
the N-terminal leader of the HtrA protease is required for export to the periplasmic space
-
Manually annotated by BRENDA team
Campylobacter jejuni NCTC11168
-
-
-
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
26000
-
SDS-PAGE, protease domain
649181
42000
-
Western blot analysis, processed protein
668373
45000
-
SDS-PAGE with coomassie staining
669100
48000
-
SDS-PAGE
651615
50000
-
SDS-PAGE
651613
50000
-
Western blot analysis, native protein
668373
50000
-
SDS-PAGE
710167
51000
-
precursor protein, SDS-PAGE
651398
200000
-
above, gel filtration
650414
274000
-
sedimentation analysis
653262
281000
-
hexameric form, gel filtration
653262
300000
-
gel filtration, 2 forms: 300000 Da and 500000 Da
649410
300000
-
gel filtration, hexameric form
651624
307000
-
recombinant enzyme, gel filtration
683471
328000
-
heptameric form, gel filtration
653262
500000
-
gel filtration, 2 forms: 300000 Da and 500000 Da
649410
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 42000, SDS-PAGE
?
-
x * 50000, SDS-PAGE
?
A6YFB5
x * 50000
?
-
x * 35000, recombinant wild-type and mutant enzyme, SDS-PAGE
?
-
x * 70000, about 70000 kDa, GST-tagged enzyme, SDS-PAGE
decamer
-
10 * 54000, SDS-PAGE, enzyme exists in 3 different forms: pentamer, hexamer and decamer
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
heptamer
-
7 * 46000, mass spectroscopy
hexamer
-
-
hexamer
-
6 * 50000, SDS-PAGE
hexamer
-
6 * 44000, gel filtration, SDS-PAGE
hexamer
-
6 * 46000, mass spectroscopy
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
-
formed by staggered association of trimeric rings
hexamer
-
two trimeric rings for a functional DegP hexamer
hexamer
-
two trimers for a hexameric structure by staggered association
hexamer
-
two trimers form a hexamer, crystallization experiments
hexamer
P26982
DegP, dimer of two trimers
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
hexamer
Salmonella enterica subsp. enterica serovar Typhimurium SL3261
-
DegP, dimer of two trimers
-
homooligomer
P0C0V0
DegP of Escherichia coli assembles into large homooligomers with an internal cavity combining both chaperone and protease activity
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
pentamer
-
5 * 54000, SDS-PAGE, enzyme exists in 3 different forms: pentamer, hexamer and decamer
tetracosamer
-
-
trimer
-
does not form hexamers like the Escherichia coli protein
trimer
-
crystal structures suggest that HtrA proteins differ in their molecular architecture, ranging from trimers with surface-accessible active sites to hexamers
homotrimer
-
-
additional information
-
HtrA contains a putative N-terminal membrane anchor domain, Ile13 to Ile26, a trypsin-like serine protease catalytic triad formed by His129, Asp158, and Ser240, and a single C-terminal PDZ domain, Gly296 to Arg385
additional information
-
secondary structures for activated protease at different temperatures
additional information
P26982
the Deg protein contain a catalytic domain with the serine protease catalytic triad, and C-terminal PDZ domains, two in DegP and DegQ, one in DegS
additional information
Salmonella enterica subsp. enterica serovar Typhimurium SL3261
-
the Deg protein contain a catalytic domain with the serine protease catalytic triad, and C-terminal PDZ domains, two in DegP and DegQ, one in DegS
-
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
proteolytic modification
-
HtrA1 activation by limited autoproteolysis, not of mutant S328A
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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
-
vapor diffusion method
-
hanging drop vapor diffusion method
-
protease domain
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10 - 25
-
low proteolytic activity is recorded for the Deg/HtrA proteases HtrA, HhoA, and HhoB at a temperature ranging from 10 to 25C
717219
20 - 45
P0C0V0
the proteolysis of casein at 20C is negligible, then it increases in almost linear fashion up to 45C. At the temperature range of 40-45C, the activity is approximately 1.5fold higher than at 37C
711285
45
-
stable for at least 4 h
651849
50
-
stable for at least 1.5 h
651849
50
D6BU29
purified recombinant DegP retains 60% of the maximum activity after incubation at 50C for 1 h
712048
55 - 75
-
denaturation of the enzyme starts at 55C and ends at 75C
651849
55
-
stable for at least 1 h
651849
60
-
drastic decrease of activity within 5 min
651849
additional information
-
interaction with phosphatidylgycerol leads to a remarkable decrease in the thermal stability
651878
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
enzyme cleaves itself under reducing conditions in the presence of 2-mercaptoethanol or dithiothreitol
-
native enzyme undergoes slow self cleavage
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Ni-NTA column chromatography
-
Ni-NTA agarose column chromatography
D6BU29
90% purity
-
near homogeneity
-
recombinant HtrA S210A mutant from overproducing strain K38
-
using Ni-NTA chromatography
-
wild-type, htrA22 and htrA63 mutant
-
wild-type, S210A and H105R mutant
-
glutathione-Sepharose bead chromatography
-
Ni-NTA column chromatography
-
recombinant His-tagged HtrA1 lacking the N-terminal insulin-like growth factor-binding protein and serine protease inhibitor domain from Escherichia coli by affinity chromatography
-
recombinant HtrA1 from 293-EBNA cell culture medium partially by ultrafiltration and dialysis
-
by Ni affinity chromatography
-
HisTrap column chromatography, gel filtration
-
Ni-NTA column chromatography and His GraviTrap affinity column chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
-
a six-gene cluster in chromosome 1 encoding a two-component regulatory system and an HtrA protease
-
expressed in Escherichia coli BL21(DE3) cells (wild type enzyme) and ion Escherichia coli BL20 cells (mutant enzyme S197A)
-
expression in Escherichia coli DH5alpha, BL20 and BL78
-
gene htrA, expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3) using a vector containing pelB secretion signal sequence
-
expressed in Escherichia coli BL21(DE3) cells
D6BU29
cloned into a Bluescript plasmid and overexpressed in Escherichia coli DH1, disrupted gene transformed to Escherichia coli Jc7623
-
cloned into pET28a
-
expressed as a C-terminal his-tagged fusion protein
-
expressed in Escherichia coli as a His-tagged fusion protein
-
overexpression of mutant S210A in strain K38
-
truncated variant lacking both PDZ domains
-
expressed in Escherichia coli
-
expressed in Escherichia coli BL21 cells
-
expressed in Escherichia coli BL21(DE3) cells
-
gene htrA, expression of His-tagged HtrA1 lacking the N-terminal insulin-like growth factor-binding protein and serine protease inhibitor domain in Escherichia coli
-
gene htrA, overexpression of wild-type and mutant enzymes in SKOV3 cells or OV202 cells
-
cloning from MC3T3-E1 cells and expression in avian myeloblastosis virus reverse transcriptase and oligo(dT) primers, overexpression in 2T3 osteoblasts and secretion of the recombinant enzyme to the cell culture medium, expression of HtrA1 in 293-EBNA cells using a mammalian episomal expression vector pCEP-His and secretion of recombinant enzyme to the culture medium
-
gene mucD is encoded in the algT-mucABCD operon, mapping of the transcriptional start site for a mucD promoter, PmucD within mucC, expression of S217A mutant single-copy gene mucD217 in strain PAO-derived mutant strains with defects in known regulators for alginate production
-
degP, DNA and amino acid sequence deterination and analysis, expression anaylsis
-
co-expression of Faa1p with Omi/HtrA in the yeast two-hybrid system, interaction analysis, overview
-
gene degP, and two paralogues degQ and degS
P26982
expressed in Escherichia coli BL21 cells
-
expression in Escherichia coli as an IPTG-inducible, recombinant protein having both N-terminal and C-terminal His6-tags
-
expression in Escherichia coli strain DH5 alpha
-
gene htrA, DNA and amino acid sequence determination and analysis
-
expressed in Escherichia coli BL21 Star (DE3) cells
-
protease domain
-
gene htrA1, DNA and amino acid sequence determination and analysis, expression in HEK-293T cells and secretion of the recombinant enzyme to the cell culture medium
A6YFB5
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
protease activity stimulates HtrA production and oligomer formation
-
protease activity stimulates HtrA production and oligomer formation
Campylobacter jejuni NCTC11168
-
-
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
-
HtrA1 mRNA and protein levels are significantly decreased in endometrial cancer compared to normal tissues
-
HtrA3 expression is reduced or completely lost in over 50% of lung cancer cell lines and primary lung tumors from heavy smokers. An increased frequency of methylation within the first exon of HtrA3 corresponds to a loss of HtrA3 expression, particularly in tumors from smokers. 4-(methylnitrosamino)-I-(3-pyridyl)-1-butanone results in HtrA3 downregulation with a corresponding increase in methylation. HtrA3 expression is reduced after 15 days of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone treatment (0.01 mM)
-
HTRA1 expression is increased in the pathogenesis of age-related macular degeneration
-
HTRA1 expression is upregulated in osteoarthritic joints, HTRA1 mRNA is increased by transforming growth factor-beta treatment (1 ng/ml for 24 h) in human primary chondrocytes
-
HtrA1 levels are highly elevated (about 7.8fold) in osteoarthritic cartilage
-
HTRA1 mRNA levels are 3fold higher in primary RPE cells homozygous for the HTRA1 promoter risk allele (rs11200638 -512 G>A), than in RPE cells with the wild type allele. This translates into a 2fold increase in HTRA1 secretion by RPE cells with the risk genotype
-
in response to loss of anchorage, HtrA1 expression is upregulated in SKOV-3 cells, resulting in autocatalytic activation. Expression of HtrA1 is upregulated during anoikis
-
the activity of isoform HTRA2 is stimulated by phosphorylation downstream of PTEN-induced putative kinase 1 and the p38 stress kinase pathway
-
treatment of HtrA3-deficient cell lines with 5-aza-2-deoxycytidine results in a dose-dependent increase in HtrA3 transcription. HtrA3 expression is induced by the histone deacetylase inhibitor LBH589
-
the growth differentiation factor 6 age-related macular degeneration risk allele (rs6982567 A) is associated with 70% increased expression of HTRA1. The HTRA1 age-related macular degeneration risk allele (rs10490924 T) is associated with 94% increased HTRA1 expression
-
HTRA3 expression is initiated on day 12 after birth and upregulated during ovarian maturation with the highest levels found in the mature cycling ovary
-
during acid stress, htrA is overexpressed in Streptococcus mutans strains K7 and UA159
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S197A
Campylobacter jejuni NCTC11168
-
protease-negative mutant protein with decreased chaperone activity compared to the wild type
-
S247A
-
proteolytically inactive mutant
C57A/C69A
-
mutant represents a completely reduced HtrA being unable to form the intramolecular S-S bond. Mutant very efficiently degrades alkaline phosphatase at 20C 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
D232V
-
the mutation causes a stimulation of proteolytic activity
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
H105R
-
loss of protease activity, no change in secondary structure
I228D
-
the mutation does not markedly affect the proteolytic activity of HtrA
I238N
-
the proteolytic activity of the mutant enzyme is undetectable
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
K455A
-
proteolytically inactive
N235I
-
the proteolytic activity of the mutant enzyme is undetectable
S210A
-
no proteolytic activity
S210A
-
loss of protease activity, no change in secondary structure
S210A
-
proteolytically inactive
S210A
-
active site residue mutant, proteolytically inactive HtrA
S210A
-
proteolytically inactive mutant
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 (30C), at which the chaperone function is proposed as being dominant
S210A
-
proteolytic activity-null mutant
S210A
P0C0V0
proteolytically inactive, the mutant does not show significant changes of the secondary structure at the temperature range 20-45C
S210A
-
the mutant lacks protease activity but retains chaperone activity
S328A
-
enzymatically inactive
S328A
-
active site mutant
S328A
-
site-directed mutagenesis, catalytically inactive mutant HtrA1
S217A
-
MucD altered in the protease motif is defective in temperature resistance and alginate gene regulation
E384K
-
naturally occuring single missense mutation in Rhodobacter capsulatus DsbA-null mutant revertant, the mutation leads to decreased protease activity, structural model
G217S
-
naturally occuring single missense mutation in Rhodobacter capsulatus DsbA-null mutant revertant, the mutation leads to decreased protease activity, structural model
G392C
-
naturally occuring single missense mutation in Rhodobacter capsulatus DsbA-null mutant revertant, the mutation leads to decreased protease activity, structural model
I120F
-
naturally occuring single missense mutation in Rhodobacter capsulatus DsbA-null mutant revertant, the mutation leads to decreased protease activity, structural model
L373S
-
naturally occuring single missense mutation in Rhodobacter capsulatus DsbA-null mutant revertant, the mutation leads to decreased protease activity, structural model
S234A
-
mutant P1386, release of competence inhibition when mutant P1388 is present alone
S237A
-
inactive mutant of HhoA
S258A
-
inactive mutant of HhoB
S237A
-
protease-inactive mutant
additional information
-
insertional inactivation of the six-gene cluster in chromosome 1 including gene htrA by recombination with a suicide plasmid, pGPOMEGATp, genetic analyses and complementation studies, overview, inactivation of the htrA gene is associated with a bacterial survival defect in vivo in a rat agar bead model of chronic lung infection
S245A
-
site-directed mutagenesis, and deletion of the HtrABCAL2829 PDZ domains result in an inactive mutant
additional information
-
mutant strain NCTC11168deltahtrA cat, main part of the HtrA gene replaced
S197A
-
protease-negative mutant protein with decreased chaperone activity compared to the wild type
additional information
Campylobacter jejuni NCTC11168
-
mutant strain NCTC11168deltahtrA cat, main part of the HtrA gene replaced
-
L229N
-
the proteolytic activity of the mutant enzyme is undetectable
additional information
-
degP null mutant strain CLC198
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
-
Escherichia coli HtrA mutant
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
additional information
-
deletion of region D232 abolishes the activity
S210A
P0C0V0
proteolytically inactive
additional information
-
downregulation of HtrA1 inovarian cancer attenuates cisplatin- and paclitaxel-induced cytotoxicity, while overexpression of HtrA1 enhances cisplatin- and paclitaxel-induced cytotoxicity
additional information
-
a genetic variation (-625G>A, rs11200638) at the HTRA1 gene promoter locus is associated with spinal disc degeneration
additional information
-
high-temperature requirement A-1 gene promoter polymorphism (G512A) is associated with age-related macular degeneration
additional information
-
HTRA1 rs11200638 gene polymorphisms confer a 10.1fold risk of age-related macular degeneration disease in the Hungarian population
additional information
-
the single nucleotide polymorphisms rs2672598, rs1049331, and rs2293870 in the HRTA1 gene are associated with age-related macular degeneration
additional information
-
mutations in the HTRA1 gene cause a hereditary cerebral small-vessel disease, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy
S328A
-
the mutation abolishes protease activity in HTRA1
additional information
-
htrA mutation in Lactococcus lactis (strain NZ9000htrA) leads to significant reduction of the efficiency of recombinant-protein secretion, as shown by recombinantly expressed streptokinase and nuclease in Lactococcus lactis
additional information
-
a htrA-deletion mutant strain shows reduced biofilm formation at high temperatures and gain sensitivity to puromycin, overview
additional information
-
a htrA-deletion mutant strain shows reduced biofilm formation at high temperatures and gain sensitivity to puromycin, overview
-
additional information
-
downregulation of HtrA1 by siRNA increases osteoblast mineralization, HtrA1 overexpression inhibits osteoblast mineral deposition in vitro and prevents BMP-2-induced mineralization, overview
additional information
-
a htrA mutant, consisting of a truncated gene, demonstrates no significant difference to the W83 parent strain when subjected to high temperature and pH values from 3 to 11. Mutant shows increased sensitivity to H2O2. HtrA mutant shows increased invasion in KB cells and gingival epithelial cells. Microarray experiments indicate that a total of 253 genes are differentially regulated in the htrA mutant, including a group of stress-related genes. In animal experiments, a competition assay shows that the htrA mutant does not survive as well as the wild-type. Fewer mice infected with the htrA mutant die than mice infected with W83, suggesting that the htrA gene is virulence-related
L382P
-
naturally occuring single missense mutation in Rhodobacter capsulatus DsbA-null mutant revertant, the mutation leads to decreased protease activity, structural model
additional information
-
the respiratory defect of Rhodobacter capsulatus DsbA-null mutants originates from the overproduction of the periplasmic protease DegP, which renders them temperature sensitive for growth, the mutants are viable and proficient in photosynthesis, phenotype, overview, overproduction of DegP abolishes the newly restored respiratory growth ability of the revertants in all growth media
V356M
-
naturally occuring single missense mutation in Rhodobacter capsulatus DsbA-null mutant revertant, the mutation leads to decreased protease activity, structural model
additional information
-
disruption of the YNM3 gene encoding Ynm3p results in increased fatty acid uptake, triglyceride accumulation, and reduced expression of the fatty acid-responsive OLE1 gene encoding the essential DELTA9-acyl-CoA desaturase, as well as in increased Faa1p and Faa4p ACSL activities, strain-specific phenotypes associated with deletion of YNM3 include the inability to grow on non-fermentable carbon sources and altered cellular morphology, overview
additional information
P26982
construction of deg deletion mutants by allelic replacement, the viability of degP and degS deletion mutants, as well as of the double mutant DELTAdegP-degS, is affected at elevated temperatures, while the degQ deletion mutant viability is not, also the triple mutant degP-degS-degQ is not severely affected, transfection of the mutants in the mouse-virulent strain SL1344 and injection into BALB/c mice, which leads attenuation of degP, degS, double, and triple mutants, while the degQ mutant is virulent as the wild-type strain, several maturally occuring mutations in the deg genes influence the virulence and pathology of Salmonella typhimurium strains, overview
additional information
Salmonella enterica subsp. enterica serovar Typhimurium SL3261
-
construction of deg deletion mutants by allelic replacement, the viability of degP and degS deletion mutants, as well as of the double mutant DELTAdegP-degS, is affected at elevated temperatures, while the degQ deletion mutant viability is not, also the triple mutant degP-degS-degQ is not severely affected, transfection of the mutants in the mouse-virulent strain SL1344 and injection into BALB/c mice, which leads attenuation of degP, degS, double, and triple mutants, while the degQ mutant is virulent as the wild-type strain, several maturally occuring mutations in the deg genes influence the virulence and pathology of Salmonella typhimurium strains, overview
-
additional information
-
mutant P1149 containing an insertion deletion mutation in the caiRH locus resulting in substantially lower HtrA expression
T230P
-
mutant P1388 with ciaH mutation
additional information
-
mutant HTR10 with in-frame deletion in htrA, mutant HTR10 is unable to efficiently process the protease proprotein, shows a dramatic increase in hemolytic activity and is virulent in a murine model of subcutaneous infection, mutant HSC11 with a deletion control strain that is a sibling of mutant HTR10 but contains wild-type htrA
additional information
-
construction of the deletion mutant HSC5DELTAhtrA
additional information
-
deletion of the PDZ domain severely impairs proteolytic activity
S296A
-
inactive mutant of HtrA
additional information
A6YFB5
HtrA knockdown promotes anterior development and impairs mesoderm and neuronal differentiation, phenotype, overview
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
HtrA is important both for adherence to and invasion of human INT407 epithelial cells
medicine
Campylobacter jejuni NCTC11168
-
HtrA is important both for adherence to and invasion of human INT407 epithelial cells
-
medicine
D6BU29
purified recombinant DegP is a protective immunogen that can induce the production of specific serum antibodies and elicit strong protective immunity in fish vaccinated with recombinant DegP
biotechnology
-
htrA mutants show improved expression of envelope-associated proteins
medicine
-
htrA mutants can act as vaccines
medicine
-
increased expression of HtrA1 in the human placenta in the third trimester of gestation, especially in the outer layer forming the syncytiotrophoblast
medicine
-
HtrA is an antigen for serum immunglobulin G during Chlamydia trachomatis sexually transmitted infection, but is not associated with pathology
medicine
-
HTRA1 is involved in osteoarthritis
medicine
-
cigarette smokeinduced methylation of HtrA3 can contribute to the etiology of chemoresistant disease in smoking-related lung cancer
molecular biology
-
instead of using an Lactococcus lactis htrA mutant, the reduction of the HtrA level in wild-type recombinant cultures of Lactococcus lactis by acid tolerace response (ATR) suppression may serve as a better strategy for the production of secreted recombinant proteins
medicine
-
HtrA1 is developmentally regulated in the uterus and trophoblast during placental establishment
molecular biology
-
htrA gene in Porphyromonas gingivalis does not relate to stress conditions such as high temperature and pH, but rather to H2O2 stress. The htrA gene is important for virulence and survival in in vivo animal models
medicine
-
aroC aroD HtrA mutant shows promise as a typhoid vaccine in humans
additional information
-
regulatory role for pneumococcal HtrA in modulating the activity of a two-component signaling system that controls the development of genetic competence