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Protein

Peroxiredoxin-6

Gene

PRDX6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.2 Publications

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.2 Publications
Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei32Important for phospholipase activity1 Publication1
Active sitei47Cysteine sulfenic acid (-SOH) intermediate; for peroxidase activity3 Publications1
Active sitei140For phospholipase activityBy similarity1

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • calcium-independent phospholipase A2 activity Source: CAFA
  • glutathione peroxidase activity Source: CAFA
  • peroxiredoxin activity Source: UniProtKB-EC
  • phospholipase A2 activity (consuming 1,2-dipalmitoylphosphatidylcholine) Source: UniProtKB-EC
  • phospholipase A2 activity consuming 1,2-dioleoylphosphatidylethanolamine) Source: UniProtKB-EC
  • protein homodimerization activity Source: CAFA
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • cell redox homeostasis Source: InterPro
  • cellular oxidant detoxification Source: CAFA
  • glycerophospholipid catabolic process Source: CAFA
  • hydrogen peroxide catabolic process Source: Ensembl
  • neutrophil degranulation Source: Reactome
  • positive regulation of mRNA splicing, via spliceosome Source: UniProtKB
  • response to oxidative stress Source: CAFA

Keywordsi

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

Enzyme and pathway databases

BRENDAi1.11.1.15 2681
ReactomeiR-HSA-3299685 Detoxification of Reactive Oxygen Species
R-HSA-6798695 Neutrophil degranulation
SIGNORiP30041

Protein family/group databases

MoonDBiP30041 Curated
MoonProtiP30041
PeroxiBasei4426 Hs1CysPrx01

Chemistry databases

SwissLipidsiSLP:000001691

Names & Taxonomyi

Protein namesi
Recommended name:
Peroxiredoxin-6 (EC:1.11.1.152 Publications)
Alternative name(s):
1-Cys peroxiredoxin
Short name:
1-Cys PRX
24 kDa protein
Acidic calcium-independent phospholipase A2 (EC:3.1.1.41 Publication)
Short name:
aiPLA2
Antioxidant protein 2
Liver 2D page spot 40
Non-selenium glutathione peroxidase
Short name:
NSGPx
Red blood cells page spot 12
Gene namesi
Name:PRDX6
Synonyms:AOP2, KIAA0106
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000117592.8
HGNCiHGNC:16753 PRDX6
MIMi602316 gene
neXtProtiNX_P30041

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Lysosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi32S → A: Loss of phospholipase activity, but no effect on peroxidase activity. 1 Publication1
Mutagenesisi47C → S: Loss of peroxidase activity, but no effect on phospholipase activity. 1 Publication1

Organism-specific databases

DisGeNETi9588
OpenTargetsiENSG00000117592
PharmGKBiPA134992760

Chemistry databases

DrugBankiDB03814 2-(N-Morpholino)-Ethanesulfonic Acid
DB02325 Isopropyl Alcohol

Polymorphism and mutation databases

BioMutaiPRDX6
DMDMi1718024

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources4 Publications
ChainiPRO_00001351022 – 224Peroxiredoxin-6Add BLAST223

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei44PhosphothreonineCombined sources1
Modified residuei63N6-acetyllysineCombined sources1
Modified residuei89PhosphotyrosineCombined sources1
Modified residuei177Phosphothreonine; by MAPKBy similarity1
Modified residuei209N6-acetyllysine; alternateCombined sources1
Modified residuei209N6-succinyllysine; alternateBy similarity1

Post-translational modificationi

Irreversibly inactivated by overoxidation of Cys-47 to sulfinic acid (Cys-SO2H) and sulfonic acid (Cys-SO3H) forms upon oxidative stress.2 Publications
Phosphorylation at Thr-177 by MAP kinases increases the phospholipase activity of the enzyme.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP30041
PaxDbiP30041
PeptideAtlasiP30041
PRIDEiP30041
ProteomicsDBi54620
TopDownProteomicsiP30041

2D gel databases

DOSAC-COBS-2DPAGEiP30041
OGPiP30041
REPRODUCTION-2DPAGEiIPI00220301
P30041
SWISS-2DPAGEiP30041

PTM databases

CarbonylDBiP30041
iPTMnetiP30041
PhosphoSitePlusiP30041
SwissPalmiP30041

Expressioni

Gene expression databases

BgeeiENSG00000117592
CleanExiHS_PRDX6
ExpressionAtlasiP30041 baseline and differential
GenevisibleiP30041 HS

Organism-specific databases

HPAiCAB008663
HPA006983

Interactioni

Subunit structurei

Homodimer (PubMed:9587003, PubMed:27353378). 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).By similarity5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • protein homodimerization activity Source: CAFA
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi114956, 94 interactors
IntActiP30041, 27 interactors
MINTiP30041
STRINGi9606.ENSP00000342026

Structurei

Secondary structure

1224
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi15 – 18Combined sources4
Beta strandi21 – 24Combined sources4
Helixi25 – 29Combined sources5
Beta strandi32 – 40Combined sources9
Helixi45 – 62Combined sources18
Turni63 – 65Combined sources3
Beta strandi66 – 74Combined sources9
Helixi76 – 89Combined sources14
Beta strandi102 – 104Combined sources3
Helixi109 – 113Combined sources5
Beta strandi117 – 122Combined sources6
Beta strandi124 – 126Combined sources3
Beta strandi128 – 130Combined sources3
Beta strandi133 – 137Combined sources5
Beta strandi141 – 148Combined sources8
Beta strandi151 – 153Combined sources3
Helixi157 – 173Combined sources17
Beta strandi175 – 177Combined sources3
Beta strandi187 – 189Combined sources3
Helixi195 – 201Combined sources7
Beta strandi219 – 221Combined sources3

3D structure databases

ProteinModelPortaliP30041
SMRiP30041
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP30041

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
GeneTreeiENSGT00550000074794
HOGENOMiHOG000022346
HOVERGENiHBG105234
InParanoidiP30041
KOiK11188
OMAiYPIIADD
OrthoDBiEOG091G0IWK
PhylomeDBiP30041
TreeFamiTF105183

Family and domain databases

InterProiView protein in InterPro
IPR000866 AhpC/TSA
IPR024706 Peroxiredoxin_AhpC-typ
IPR019479 Peroxiredoxin_C
IPR036249 Thioredoxin-like_sf
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.

P30041-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPGGLLLGDV APNFEANTTV GRIRFHDFLG DSWGILFSHP RDFTPVCTTE
60 70 80 90 100
LGRAAKLAPE FAKRNVKLIA LSIDSVEDHL AWSKDINAYN CEEPTEKLPF
110 120 130 140 150
PIIDDRNREL AILLGMLDPA EKDEKGMPVT ARVVFVFGPD KKLKLSILYP
160 170 180 190 200
ATTGRNFDEI LRVVISLQLT AEKRVATPVD WKDGDSVMVL PTIPEEEAKK
210 220
LFPKGVFTKE LPSGKKYLRY TPQP
Length:224
Mass (Da):25,035
Last modified:January 23, 2007 - v3
Checksum:i017D955F0FEEDFBC
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D14662 mRNA Translation: BAA03496.1
DQ230990 Genomic DNA Translation: ABB02185.1
AL139142 Genomic DNA No translation available.
AK289352 mRNA Translation: BAF82041.1
CH471067 Genomic DNA Translation: EAW90944.1
BC035857 mRNA Translation: AAH35857.1
BC053550 mRNA Translation: AAH53550.1
AJ844621 mRNA Translation: CAH59743.1
CCDSiCCDS1307.1
RefSeqiNP_004896.1, NM_004905.2
UniGeneiHs.120
Hs.731505

Genome annotation databases

EnsembliENST00000340385; ENSP00000342026; ENSG00000117592
GeneIDi9588
KEGGihsa:9588

Similar proteinsi

Entry informationi

Entry nameiPRDX6_HUMAN
AccessioniPrimary (citable) accession number: P30041
Secondary accession number(s): A8JZY7
, P32077, Q5TAH4, Q5ZEZ8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: January 23, 2007
Last modified: July 18, 2018
This is version 198 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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