P30041 · PRDX6_HUMAN
- ProteinPeroxiredoxin-6
- GenePRDX6
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids224 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively (PubMed:10893423, PubMed:9497358).
Can reduce H2O2 and short chain organic, fatty acid, and phospholipid hydroperoxides (PubMed:10893423).
Also has phospholipase activity, can therefore either reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or hydrolyze the sn-2 ester bond of phospholipids (phospholipase activity) (PubMed:10893423, PubMed:26830860).
These activities are dependent on binding to phospholipids at acidic pH and to oxidized phospholipds at cytosolic pH (PubMed:10893423).
Plays a role in cell protection against oxidative stress by detoxifying peroxides and in phospholipid homeostasis (PubMed:10893423).
Exhibits acyl-CoA-dependent lysophospholipid acyltransferase which mediates the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC) (PubMed:26830860).
Shows a clear preference for LPC as the lysophospholipid and for palmitoyl CoA as the fatty acyl substrate (PubMed:26830860).
Can reduce H2O2 and short chain organic, fatty acid, and phospholipid hydroperoxides (PubMed:10893423).
Also has phospholipase activity, can therefore either reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or hydrolyze the sn-2 ester bond of phospholipids (phospholipase activity) (PubMed:10893423, PubMed:26830860).
These activities are dependent on binding to phospholipids at acidic pH and to oxidized phospholipds at cytosolic pH (PubMed:10893423).
Plays a role in cell protection against oxidative stress by detoxifying peroxides and in phospholipid homeostasis (PubMed:10893423).
Exhibits acyl-CoA-dependent lysophospholipid acyltransferase which mediates the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC) (PubMed:26830860).
Shows a clear preference for LPC as the lysophospholipid and for palmitoyl CoA as the fatty acyl substrate (PubMed:26830860).
Miscellaneous
The active site is a conserved redox-active cysteine residue, the peroxidatic cysteine (C(P)), which makes the nucleophilic attack on the peroxide substrate. The peroxide oxidizes the C(P)-SH to cysteine sulfenic acid (C(P)-SOH), which then reacts with another cysteine residue, the resolving cysteine (C(R)), to form a disulfide bridge. The disulfide is subsequently reduced by an appropriate electron donor to complete the catalytic cycle. In this 1-Cys peroxiredoxin, no C(R) is present and C(P) instead forms a disulfide with a cysteine from another protein or with a small thiol molecule. C(P) is reactivated by glutathionylation mediated by glutathione S-transferase Pi, followed by spontaneous reduction of the enzyme with glutathione.
Catalytic activity
- a hydroperoxide + 2 glutathione = an alcohol + glutathione disulfide + H2O
- 1-hexadecanoyl-sn-glycero-3-phosphocholine + hexadecanoyl-CoA = 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + CoAThis reaction proceeds in the forward direction.
- 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + H+ + hexadecanoateThis reaction proceeds in the forward direction.
Activity regulation
MJ33 or lithium;[(2R)-1-hexadecoxy-3-(2,2,2-trifluoroethoxy)propan-2-yl] methyl phosphate inhibits its phospholipase A2 activity (PubMed:26830860).
CI-976 or 2,2-Dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide inhibits its lysophosphatidylcholine acyltransferase activity (PubMed:26830860).
CI-976 or 2,2-Dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide inhibits its lysophosphatidylcholine acyltransferase activity (PubMed:26830860).
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
18 μM | palmitoyl-CoA | 4.0 | lysophosphatidylcholine acyltransferase activity | |||
15 μM | palmitoyl-CoA | 7.0 | lysophosphatidylcholine acyltransferase activity for the phosphorylated form |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
30 nmol/min/mg | 4.0 | with palmitoyl-CoA as substrate for lysophosphatidylcholine acyltransferase activity | |||
770 nmol/min/mg | 7.0 | with palmitoyl-CoA as substrate for lysophosphatidylcholine acyltransferase activity, phosphorylated form |
pH Dependence
Shows a 3-fold greater lysophosphatidylcholine acyltransferase activity at pH 4.0 than at pH 7.0.
Features
Showing features for site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 32 | Important for phospholipase activity | ||||
Sequence: S | ||||||
Active site | 47 | Cysteine sulfenic acid (-SOH) intermediate; for peroxidase activity | ||||
Sequence: C | ||||||
Active site | 140 | For phospholipase activity | ||||
Sequence: D |
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
Chemistry
Names & Taxonomy
Protein names
- Recommended namePeroxiredoxin-6
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP30041
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 32 | Loss of phospholipase activity, but no effect on peroxidase activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 47 | Loss of peroxidase activity, but no effect on phospholipase activity. | ||||
Sequence: C → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 201 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Chain | PRO_0000135102 | 2-224 | UniProt | Peroxiredoxin-6 | |||
Sequence: PGGLLLGDVAPNFEANTTVGRIRFHDFLGDSWGILFSHPRDFTPVCTTELGRAAKLAPEFAKRNVKLIALSIDSVEDHLAWSKDINAYNCEEPTEKLPFPIIDDRNRELAILLGMLDPAEKDEKGMPVTARVVFVFGPDKKLKLSILYPATTGRNFDEILRVVISLQLTAEKRVATPVDWKDGDSVMVLPTIPEEEAKKLFPKGVFTKELPSGKKYLRYTPQP | |||||||
Modified residue | 44 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 44 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 63 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 89 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 89 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 146 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 177 | UniProt | Phosphothreonine; by MAPK | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 177 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 186 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 208 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 209 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Modified residue | 209 | UniProt | N6-succinyllysine; alternate | ||||
Sequence: K |
Post-translational modification
Irreversibly inactivated by overoxidation of Cys-47 to sulfinic acid (Cys-SO2H) and sulfonic acid (Cys-SO3H) forms upon oxidative stress.
Phosphorylation at Thr-177 by MAP kinases increases the phospholipase activity of the enzyme (By similarity).
The phosphorylated form exhibits a greater lysophosphatidylcholine acyltransferase activity compared to the non-phosphorylated form (PubMed:26830860).
The phosphorylated form exhibits a greater lysophosphatidylcholine acyltransferase activity compared to the non-phosphorylated form (PubMed:26830860).
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Interaction
Subunit
Homodimer (PubMed:27353378, PubMed:9587003).
Interacts with GSTP1; mediates PRDX6 glutathionylation and regeneration (By similarity).
Interacts with APEX1 (PubMed:19188445).
Interacts with STH (PubMed:16186110).
May interact with FAM168B (PubMed:20716133).
May interact with HTR2A (By similarity).
Interacts with GSTP1; mediates PRDX6 glutathionylation and regeneration (By similarity).
Interacts with APEX1 (PubMed:19188445).
Interacts with STH (PubMed:16186110).
May interact with FAM168B (PubMed:20716133).
May interact with HTR2A (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P30041 | ARFGAP3 Q9NP61 | 3 | EBI-2255129, EBI-2875816 | |
BINARY | P30041 | COX15 Q7KZN9 | 3 | EBI-2255129, EBI-3248549 | |
BINARY | P30041 | DLD P09622 | 3 | EBI-2255129, EBI-353366 | |
XENO | P30041 | PRO_0000308465 P29991 | 3 | EBI-2255129, EBI-8826747 | |
BINARY | P30041 | PCNA P12004 | 2 | EBI-2255129, EBI-358311 | |
BINARY | P30041 | PSMD8 P48556 | 3 | EBI-2255129, EBI-359304 | |
BINARY | P30041 | TERF1 P54274 | 2 | EBI-2255129, EBI-710997 | |
BINARY | P30041 | VDAC1 P21796 | 3 | EBI-2255129, EBI-354158 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 5-169 | Thioredoxin | ||||
Sequence: LLLGDVAPNFEANTTVGRIRFHDFLGDSWGILFSHPRDFTPVCTTELGRAAKLAPEFAKRNVKLIALSIDSVEDHLAWSKDINAYNCEEPTEKLPFPIIDDRNRELAILLGMLDPAEKDEKGMPVTARVVFVFGPDKKLKLSILYPATTGRNFDEILRVVISLQL | ||||||
Region | 31-40 | Required and sufficient for targeting to lysosomes and lamellar bodies | ||||
Sequence: DSWGILFSHP |
Sequence similarities
Belongs to the peroxiredoxin family. Prx6 subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length224
- Mass (Da)25,035
- Last updated2007-01-23 v3
- Checksum017D955F0FEEDFBC
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
D14662 EMBL· GenBank· DDBJ | BAA03496.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ230990 EMBL· GenBank· DDBJ | ABB02185.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AL139142 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AK289352 EMBL· GenBank· DDBJ | BAF82041.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471067 EMBL· GenBank· DDBJ | EAW90944.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC035857 EMBL· GenBank· DDBJ | AAH35857.1 EMBL· GenBank· DDBJ | mRNA | ||
BC053550 EMBL· GenBank· DDBJ | AAH53550.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ844621 EMBL· GenBank· DDBJ | CAH59743.1 EMBL· GenBank· DDBJ | mRNA |