P30041 · PRDX6_HUMAN

  • Protein
    Peroxiredoxin-6
  • Gene
    PRDX6
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

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

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).

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
18 μMpalmitoyl-CoA4.0lysophosphatidylcholine acyltransferase activity
15 μMpalmitoyl-CoA7.0lysophosphatidylcholine acyltransferase activity for the phosphorylated form
Vmax pH TEMPERATURE[C] NOTES EVIDENCE
30 nmol/min/mg4.0with palmitoyl-CoA as substrate for lysophosphatidylcholine acyltransferase activity
770 nmol/min/mg7.0with 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.

TypeIDPosition(s)Description
Site32Important for phospholipase activity
Active site47Cysteine sulfenic acid (-SOH) intermediate; for peroxidase activity
Active site140For phospholipase activity

GO annotations

AspectTerm
Cellular Componentazurophil granule lumen
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentextracellular exosome
Cellular Componentextracellular region
Cellular Componentextracellular space
Cellular Componentmembrane
Cellular Componentmitochondrion
Cellular Componentnucleus
Cellular Componentperinuclear region of cytoplasm
Molecular Function1-acylglycerophosphocholine O-acyltransferase activity
Molecular Functioncadherin binding
Molecular Functioncalcium-independent phospholipase A2 activity
Molecular Functionglutathione peroxidase activity
Molecular Functionidentical protein binding
Molecular Functionperoxiredoxin activity
Molecular Functionphospholipase A2 activity
Molecular Functionubiquitin protein ligase binding
Biological Processcell redox homeostasis
Biological Processcellular oxidant detoxification
Biological Processglycerophospholipid catabolic process
Biological Processpositive regulation of mRNA splicing, via spliceosome
Biological Processresponse to oxidative stress

Keywords

Enzyme and pathway databases

Protein family/group databases

Chemistry

Names & Taxonomy

Protein names

  • Recommended name
    Peroxiredoxin-6
  • EC number
  • Alternative names
    • 1-Cys peroxiredoxin (1-Cys PRX)
    • 24 kDa protein
    • Acidic calcium-independent phospholipase A2 (aiPLA2) (EC:3.1.1.4
      ) . EC:3.1.1.4 (UniProtKB | ENZYME | Rhea)
    • Antioxidant protein 2
    • Glutathione-dependent peroxiredoxin

Gene names

    • Name
      PRDX6
    • Synonyms
      AOP2, KIAA0106

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P30041
  • Secondary accessions
    • A8JZY7
    • P32077
    • Q5TAH4
    • Q5ZEZ8

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Disease & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis32Loss of phospholipase activity, but no effect on peroxidase activity.
Mutagenesis47Loss of peroxidase activity, but no effect on phospholipase activity.

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.

Go to variant viewer

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for initiator methionine, chain, modified residue, modified residue (large scale data).

TypeIDPosition(s)SourceDescription
Initiator methionine1UniProtRemoved
ChainPRO_00001351022-224UniProtPeroxiredoxin-6
Modified residue44UniProtPhosphothreonine
Modified residue (large scale data)44PRIDEPhosphothreonine
Modified residue63UniProtN6-acetyllysine
Modified residue89UniProtPhosphotyrosine
Modified residue (large scale data)89PRIDEPhosphotyrosine
Modified residue (large scale data)146PRIDEPhosphoserine
Modified residue177UniProtPhosphothreonine; by MAPK
Modified residue (large scale data)177PRIDEPhosphothreonine
Modified residue (large scale data)186PRIDEPhosphoserine
Modified residue (large scale data)208PRIDEPhosphothreonine
Modified residue209UniProtN6-acetyllysine; alternate
Modified residue209UniProtN6-succinyllysine; alternate

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).

Keywords

Proteomic databases

2D gel databases

PTM databases

Expression

Gene expression databases

Organism-specific databases

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).

Binary interactions

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for domain, region.

TypeIDPosition(s)Description
Domain5-169Thioredoxin
Region31-40Required and sufficient for targeting to lysosomes and lamellar bodies

Sequence similarities

Belongs to the peroxiredoxin family. Prx6 subfamily.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    224
  • Mass (Da)
    25,035
  • Last updated
    2007-01-23 v3
  • Checksum
    017D955F0FEEDFBC
MPGGLLLGDVAPNFEANTTVGRIRFHDFLGDSWGILFSHPRDFTPVCTTELGRAAKLAPEFAKRNVKLIALSIDSVEDHLAWSKDINAYNCEEPTEKLPFPIIDDRNRELAILLGMLDPAEKDEKGMPVTARVVFVFGPDKKLKLSILYPATTGRNFDEILRVVISLQLTAEKRVATPVDWKDGDSVMVLPTIPEEEAKKLFPKGVFTKELPSGKKYLRYTPQP

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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