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Protein

Peroxiredoxin-6

Gene

Prdx6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Can reduce H2O2 and short chain organic, fatty acid, and phospholipid hydroperoxides. Also has phospholipase activity, and can therefore either reduce the oxidized sn-2 fatty acyl grup of phospholipids (peroxidase activity) or hydrolyze the sn-2 ester bond of phospholipids (phospholipase activity). These activities are dependent on binding to phospholipids at acidic pH and to oxidized phospholipds at cytosolic pH. Plays a role in cell protection against oxidative stress by detoxifying peroxides and in phospholipid homeostasis.By similarity

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.By similarity

Catalytic activityi

2 R'-SH + ROOH = R'-S-S-R' + H2O + ROH.By similarity
Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei32Important for phospholipase activityBy similarity1
Active sitei47Cysteine sulfenic acid (-SOH) intermediate; for peroxidase activityBy similarity1
Active sitei140For phospholipase activityBy similarity1

GO - Molecular functioni

GO - Biological processi

  • bleb assembly Source: MGI
  • cell redox homeostasis Source: InterPro
  • cellular oxidant detoxification Source: MGI
  • glycerophospholipid catabolic process Source: MGI
  • response to oxidative stress Source: MGI
  • response to reactive oxygen species Source: MGI

Keywordsi

Molecular functionAntioxidant, Hydrolase, Oxidoreductase, Peroxidase
Biological processLipid degradation, Lipid metabolism

Enzyme and pathway databases

BRENDAi1.11.1.15. 3474.

Names & Taxonomyi

Protein namesi
Recommended name:
Peroxiredoxin-6 (EC:1.11.1.15)
Alternative name(s):
1-Cys peroxiredoxin
Short name:
1-Cys PRX
Acidic calcium-independent phospholipase A2 (EC:3.1.1.4)
Short name:
aiPLA2
Antioxidant protein 2
Non-selenium glutathione peroxidase
Short name:
NSGPx
Gene namesi
Name:Prdx6
Synonyms:Aop2, Ltw4, Prdx5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:894320. Prdx6.

Subcellular locationi

  • Cytoplasm By similarity
  • Lysosome By similarity

  • Note: Also found in lung secretory organelles (lamellar bodies).By similarity

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytoplasmic vesicle Source: UniProtKB-KW
  • cytosol Source: MGI
  • extracellular exosome Source: MGI
  • extracellular space Source: MGI
  • lysosome Source: UniProtKB-SubCell
  • membrane Source: MGI
  • mitochondrion Source: MGI

Keywords - Cellular componenti

Cytoplasm, Lysosome

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00001351032 – 224Peroxiredoxin-6Add BLAST223

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei44PhosphothreonineBy similarity1
Modified residuei63N6-acetyllysineBy similarity1
Modified residuei89PhosphotyrosineCombined sources1
Modified residuei93PhosphothreonineCombined sources1
Modified residuei177Phosphothreonine; by MAPKBy similarity1
Modified residuei209N6-acetyllysine; alternateBy similarity1
Modified residuei209N6-succinyllysine; alternateCombined sources1

Post-translational modificationi

Irreversibly inactivated by overoxidation of Cys-47 to sulfinic acid (Cys-SO2H) and sulfonic acid (Cys-SO3H) forms upon oxidative stress.By similarity
Phosphorylation at Thr-177 by MAP kinases increases the phospholipase activity of the enzyme.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO08709.
MaxQBiO08709.
PaxDbiO08709.
PeptideAtlasiO08709.
PRIDEiO08709.
TopDownProteomicsiO08709.

2D gel databases

COMPLUYEAST-2DPAGEiO08709.
REPRODUCTION-2DPAGEiO08709.
SWISS-2DPAGEiO08709.
UCD-2DPAGEiO08709.

PTM databases

iPTMnetiO08709.
PhosphoSitePlusiO08709.
SwissPalmiO08709.

Expressioni

Tissue specificityi

Highly expressed in heart, kidney and liver. Moderate expression in brain and stomach. Very low levels in intestine.

Gene expression databases

CleanExiMM_PRDX5.
MM_PRDX6.

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with GSTP1; mediates PRDX6 glutathionylation and regeneration (By similarity). Interacts with APEX1. Interacts with STH. May interact with FAM168B (By similarity). May interact with HTR2A (PubMed:14988405).By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198118. 3 interactors.
IntActiO08709. 9 interactors.
MINTiMINT-1869428.
STRINGi10090.ENSMUSP00000071636.

Structurei

3D structure databases

ProteinModelPortaliO08709.
SMRiO08709.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini5 – 169ThioredoxinPROSITE-ProRule annotationAdd BLAST165

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni31 – 40Required and sufficient for targeting to lysosomes and lamellar bodiesBy similarity10

Sequence similaritiesi

Belongs to the peroxiredoxin family. Prx6 subfamily.Curated

Keywords - Domaini

Redox-active center

Phylogenomic databases

eggNOGiKOG0854. Eukaryota.
COG0450. LUCA.
HOVERGENiHBG105234.
InParanoidiO08709.
KOiK11188.

Family and domain databases

InterProiView protein in InterPro
IPR000866. AhpC/TSA.
IPR024706. Peroxiredoxin_AhpC-typ.
IPR019479. Peroxiredoxin_C.
IPR012336. Thioredoxin-like_fold.
IPR013766. Thioredoxin_domain.
PfamiView protein in Pfam
PF10417. 1-cysPrx_C. 1 hit.
PF00578. AhpC-TSA. 1 hit.
PIRSFiPIRSF000239. AHPC. 1 hit.
SUPFAMiSSF52833. SSF52833. 1 hit.
PROSITEiView protein in PROSITE
PS51352. THIOREDOXIN_2. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O08709-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPGGLLLGDE APNFEANTTI GRIRFHDFLG DSWGILFSHP RDFTPVCTTE
60 70 80 90 100
LGRAAKLAPE FAKRNVKLIA LSIDSVEDHL AWSKDINAYN GETPTEKLPF
110 120 130 140 150
PIIDDKGRDL AILLGMLDPV EKDDNNMPVT ARVVFIFGPD KKLKLSILYP
160 170 180 190 200
ATTGRNFDEI LRVVDSLQLT GTKPVATPVD WKKGESVMVV PTLSEEEAKQ
210 220
CFPKGVFTKE LPSGKKYLRY TPQP
Length:224
Mass (Da):24,871
Last modified:January 23, 2007 - v3
Checksum:iAECDEDD332858B8F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti154G → S in AAC67553 (PubMed:10395907).Curated1
Sequence conflicti181W → R in AAD03716 (PubMed:10395907).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti124D → A in strain: C57BL/6, C57BL/6J and FVB/N. Combined sources1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF004670 mRNA. Translation: AAC53277.1.
Y12883 mRNA. Translation: CAA73383.1.
AF093852 mRNA. Translation: AAC63376.1.
AF093853 Genomic DNA. Translation: AAC67553.1.
AF093857
, AF093854, AF093855, AF093856 Genomic DNA. Translation: AAD03716.1.
AK030413 mRNA. Translation: BAC26952.1.
BC013489 mRNA. Translation: AAH13489.1.
CCDSiCCDS15415.1.
RefSeqiNP_031479.1. NM_007453.4.
UniGeneiMm.186185.

Genome annotation databases

GeneIDi11758.
KEGGimmu:11758.

Similar proteinsi

Entry informationi

Entry nameiPRDX6_MOUSE
AccessioniPrimary (citable) accession number: O08709
Secondary accession number(s): Q91WT2, Q9QWP4, Q9QWW0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 23, 2007
Last modified: August 30, 2017
This is version 161 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Multifunctional enzyme, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families