Any feedback?
Information on EC 1.11.1.27 - glutathione-dependent peroxiredoxin and Organism(s) Mus musculus and UniProt Accession O08709
for references in articles please use BRENDA:EC1.11.1.27Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.11.1.27 glutathione-dependent peroxiredoxinIUBMB Comments
Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant proteins. They can be divided into three classes: typical 2-Cys, atypical 2-Cys and 1-Cys peroxiredoxins . The peroxidase reaction comprises two steps centred around a redox-active cysteine called the peroxidatic cysteine. All three peroxiredoxin classes have the first step in common, in which the peroxidatic cysteine attacks the peroxide substrate and is oxidized to S-hydroxycysteine (a sulfenic acid) (see {single/111115a::mechanism}). The second step of the peroxidase reaction, the regeneration of cysteine from S-hydroxycysteine, distinguishes the three peroxiredoxin classes. For typical 2-Cys Prxs, in the second step, the peroxidatic S-hydroxycysteine from one subunit is attacked by the 'resolving' cysteine located in the C-terminus of the second subunit, to form an intersubunit disulfide bond, which is then reduced by one of several cell-specific thiol-containing reductants completing the catalytic cycle. In the atypical 2-Cys Prxs, both the peroxidatic cysteine and its resolving cysteine are in the same polypeptide, so their reaction forms an intrachain disulfide bond. The 1-Cys Prxs conserve only the peroxidatic cysteine, so its regeneration involves direct interaction with a reductant molecule. Glutathione-dependent peroxiredoxins have been reported from bacteria and animals, and appear to be 1-Cys enzymes. The mechanism for the mammalian PRDX6 enzyme involves heterodimerization of the enzyme with pi-glutathione S-transferase, followed by glutathionylation of the oxidized cysteine residue. Subsequent dissociation of the heterodimer yields glutathionylated peroxiredoxin, which is restored to the active form via spontaneous reduction by a second glutathione molecule.
Specify your search results
Word Map
- 1.11.1.27
- peroxiredoxins
- plasmodium
- falciparum
-
malaria
- prxvi
-
intraerythrocytic
- medicine
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
pf1-cys-prx, peroxiredoxin vi, 1-cys prdx, hi0572, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Prdx6
peroxiredoxin 6
Prdx6
Prx3
-
-
-
-
peroxiredoxin 6
-
dual function enzyme with independent glutathione peroxidase and phospholipase A2 activities
Prdx6
-
-
-
-
Prdx6
-
Prdx6 is the prototype and the only mammalian 1-Cys member of the peroxiredoxin family
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
glutathione:hydroperoxide oxidoreductase
Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant proteins. They can be divided into three classes: typical 2-Cys, atypical 2-Cys and 1-Cys peroxiredoxins [1]. The peroxidase reaction comprises two steps centred around a redox-active cysteine called the peroxidatic cysteine. All three peroxiredoxin classes have the first step in common, in which the peroxidatic cysteine attacks the peroxide substrate and is oxidized to S-hydroxycysteine (a sulfenic acid) (see {single/111115a::mechanism}). The second step of the peroxidase reaction, the regeneration of cysteine from S-hydroxycysteine, distinguishes the three peroxiredoxin classes. For typical 2-Cys Prxs, in the second step, the peroxidatic S-hydroxycysteine from one subunit is attacked by the 'resolving' cysteine located in the C-terminus of the second subunit, to form an intersubunit disulfide bond, which is then reduced by one of several cell-specific thiol-containing reductants completing the catalytic cycle. In the atypical 2-Cys Prxs, both the peroxidatic cysteine and its resolving cysteine are in the same polypeptide, so their reaction forms an intrachain disulfide bond. The 1-Cys Prxs conserve only the peroxidatic cysteine, so its regeneration involves direct interaction with a reductant molecule. Glutathione-dependent peroxiredoxins have been reported from bacteria and animals, and appear to be 1-Cys enzymes. The mechanism for the mammalian PRDX6 enzyme involves heterodimerization of the enzyme with pi-glutathione S-transferase, followed by glutathionylation of the oxidized cysteine residue. Subsequent dissociation of the heterodimer yields glutathionylated peroxiredoxin, which is restored to the active form via spontaneous reduction by a second glutathione molecule.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2 GSH + ROOH
GSSG + H2O + ROH
-
glutathione is the primary native reductant
-
-
?
additional information
?
-
the enzyme functions in antioxidant defense and lung phospholipid metabolism
-
-
?
additional information
?
-
-
the 1-Cys Prdx type Prdx6, possessing a single conserved cysteine residue, shows heterodimerization with piGSH S-transferase as part of the catalytic cycle, and the ability to either reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or to hydrolyze the sn-2 ester (alkyl) bond of phospholipids (PLA2 activity), thus exhiting peroxidase and phospholipase activities, overview. The bifunctional protein has separate active sites for both activities, namely a Cys 47-dependent peroxidase activity site and a Ser32-dependent PLA2 activity site. Substrate specificity, overview
-
-
?
additional information
?
-
-
DTT is not a physiological reductant and thioredoxin, the reductant that is active in the catalytic cycle for the 2-Cys peroxiredoxins, is not effective as a reductant for 1-Cys Prdx6. Prdx6 binds and reduces phospholipid hydroperoxides. Prdx6 reduces H2O2 and other short chain hydroperoxides. The conserved Cys in Prdx6 is buried at the base of a narrow pocket. This location renders it unable to dimerize through disulfide formation in the native configuration but homodimers (and multimers) can arise through hydrophobic interactions. Disulfide formation may occur with denatured proteins and heterodimerization also occurs normally as part of the catalytic cycle. The protein also contains a surface expressed catalytic triad, S-D-H, that is important for phospholipid binding and enzymatic activities
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2 GSH + ROOH
GSSG + H2O + ROH
-
glutathione is the primary native reductant
-
-
?
additional information
?
-
the enzyme functions in antioxidant defense and lung phospholipid metabolism
-
-
?
additional information
?
-
-
the 1-Cys Prdx type Prdx6, possessing a single conserved cysteine residue, shows heterodimerization with piGSH S-transferase as part of the catalytic cycle, and the ability to either reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or to hydrolyze the sn-2 ester (alkyl) bond of phospholipids (PLA2 activity), thus exhiting peroxidase and phospholipase activities, overview. The bifunctional protein has separate active sites for both activities, namely a Cys 47-dependent peroxidase activity site and a Ser32-dependent PLA2 activity site. Substrate specificity, overview
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Mercaptosuccinate
-
a thiol-active agent that inhibits the peroxidase activity of Prdx6 while the PLA2 activity is unaffected
MJ33
-
a phospholipid substrate intermediate analogue, inhibits the PLA2 activity of Prdx6 but has no effect on peroxidase activity
additional information
-
serine protease inhibitors inhibit the PLA2 activity of Prdx6 but have no effect on peroxidase activity
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
bifunctional protein with glutathione peroxidase activity and phospholipase A2 activity
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
especially in type II alveolar epithelial cells and bronchiolar Clara cells
additional information
-
within organs, expression of Prdx is greatest in epithelium such as apical regions of respiratory epithelium and skin epidermis, tissue distribution, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
cytosolic Prdx6 could bind to and reduce peroxidized membrane phospholipids followed by its dissociation from the membrane and return to the cytosolic compartment
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
Prdx6 null mice show increased lung or liver injury with exposure to hyperoxia, lipopolysaccharide (LPS), or paraquat. Prdx6 null mice as compared to wild type demonstrate increased age-related oxidative damage to their sperm chromatin
physiological function
malfunction
-
enzyme haplodeficiency attenuates astro- and microglia activation around Abeta plaques promoting Abeta deposition and neuritic degeneration
physiological function
additional information
-
regulation of Prdx6 gene regulation, overview. Transcription is activated by binding of the transcription factor Nrf2 to the ARE whereas transcription is inhibited by the binding of Nrf3. Prdx6 expression also is responsive to hormonal regulation
physiological function
cells over-expressing Prdx6 show an increase in survival compared to control when oxidatively challenged with hydroperoxides, paraquat, UVB radiation, or OH generated by Cu2+/ascorbate. Prx6 over-expression through adenoviral-mediated intratracheal delivery of a Prdx6 expression vector or in transgenic mice protected lungs from hyperoxic injury. Prdx6 has an important role in the repair of peroxidized cell membranes, at least in lungs, and that both its PHGPx and PLA2 activities play important roles
physiological function
Prdx6 plays crucial roles in lung phospholipid metabolism, lipid peroxidation repair, and inflammatory signaling. Mice that over-express Prdx6 show a greater increase in the growth of lung tumors compared to wild-type animals. Both aiPLA2 and Prdx6 peroxidase activities are implicated in lung tumor development through the regulation of redox-sensitive pathways such as MAPK, JNK, JAK/STAT, and AP-1
physiological function
-
Prdx6 has important roles in both antioxidant defense based on its ability to reduce peroxidized membrane phospholipids and in phospholipid homeostasis based on its ability to generate lysophospholipid substrate for the remodeling pathway of phospholipid synthesis
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PRDX6_MOUSE
224
0
24871
Swiss-Prot
other Location (Reliability: 1)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
-
MAP kinase mediated phosphorylation of Prdx6 at residue T177, results in increased phospholipase A2 activity, but phosphorylation has no effect on the peroxidase activity of Prdx6
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
peroxiredoxin 6 is a bifunctional protein with glutathione peroxidase activity and phospholipase A2 activity. A Prdx6 enzyme with a single activity is constructed to facilitate study of the relationship between the single function of Prdx6 and Brucella infection. The target open reading frame DNAs of Prdx6 with a single active centre are prepared using gene splicing by overlap extension PCR, and the recombinant eukaryotic expression plasmids inserted by Prdx6 with the single activity centre are constructed and transfected into murine Raw264.7 macrophages. The glutathione peroxidase activity and phospholipase A2 activity of the constructed Prdx6 are examined. The core centres (Ser32 and Cys47) of Prdx6 are successfully mutated by changing the 94th nucleotide from T to G and the 140th nucleotide from G to C in the two enzyme activity cores, respectively. The constructed recombinant plasmids of Prdx6 with the single active centre are transfected into murine macrophages showing the expected single functional enzyme activity, which MJ33 or mercaptosuccinate inhibitors are able to inhibit
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
Prdx6 gene, DNA and amino acid sequence determination and analysis, comprises 5 exons and 4 introns and is located on chromosome 1, mapped to a 0.66 cM interval between D1Mit 159 and D1Mit 398, sequence comparison
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
oxidant stress is, e.g. by H2O2, paraquat, a potent inducer of Prdx6 expression and stimulates Prdx6 gene expression by a transcriptional mechanism involving its antioxidant response element, ARE
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Manevich, Y.; Fisher, A.B.
Peroxiredoxin 6, a 1-Cys peroxiredoxin, functions in antioxidant defense and lung phospholipid metabolism
Free Radic. Biol. Med.
38
1422-1432
2005
Bos taurus (O77834), Homo sapiens (P30041), Mus musculus (O08709), Rattus norvegicus (O35244), Sus scrofa (Q9TSX9)
Fisher, A.B.
Peroxiredoxin 6: A bifunctional enzyme with glutathione peroxidase and phospholipase A2 activities
Antioxid. Redox Signal.
15
831-844
2010
Bos taurus, Homo sapiens, Mus musculus, Rattus norvegicus
Arevalo, J.A.; Vazquez-Medina, J.P.
The role of peroxiredoxin 6 in cell signaling
Antioxidants (Basel)
7
172
2018
Mus musculus (O08709), Homo sapiens (P30041)
Fisher, A.B.
Peroxiredoxin 6 in the repair of peroxidized cell membranes and cell signaling
Arch. Biochem. Biophys.
617
68-83
2017
Mus musculus (O08709)
Wang, L.L.; Lu, S.Y.; Hu, P.; Fu, B.Q.; Li, Y.S.; Zhai, F.F.; Ju, D.D.; Zhang, S.J.; Su, B.; Zhou, Y.; Liu, Z.S.; Ren, H.L.
Construction and activity analyses of single functional mouse peroxiredoxin 6 (Prdx6)
J. Vet. Res.
63
99-105
2019
Mus musculus (O08709)
EXTERNAL LINKS (specific for EC-Number 1.11.1.27)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
