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Protein

Thioredoxin-dependent peroxide reductase, mitochondrial

Gene

PRDX3

Organism
Homo sapiens (Human)
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. Plays a role in cell protection against oxidative stress by detoxifying peroxides (PubMed:7733872, PubMed:17707404). Acts synergistically with MAP3K13 to regulate the activation of NF-kappa-B in the cytosol (PubMed:12492477).3 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 typical 2-Cys peroxiredoxin, C(R) is provided by the other dimeric subunit to form an intersubunit disulfide. The disulfide is subsequently reduced by thioredoxin.1 Publication

Catalytic activityi

2 R'-SH + ROOH = R'-S-S-R' + H2O + ROH.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei108Cysteine sulfenic acid (-SOH) intermediateBy similarity1

GO - Molecular functioni

  • alkyl hydroperoxide reductase activity Source: UniProtKB
  • cysteine-type endopeptidase inhibitor activity involved in apoptotic process Source: UniProtKB
  • identical protein binding Source: IntAct
  • kinase binding Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • thioredoxin peroxidase activity Source: ParkinsonsUK-UCL

GO - Biological processi

  • cell redox homeostasis Source: InterPro
  • cellular response to oxidative stress Source: ParkinsonsUK-UCL
  • cellular response to reactive oxygen species Source: UniProtKB
  • hydrogen peroxide catabolic process Source: MGI
  • maternal placenta development Source: Ensembl
  • mitochondrion organization Source: UniProtKB
  • myeloid cell differentiation Source: UniProtKB
  • negative regulation of apoptotic process Source: ParkinsonsUK-UCL
  • negative regulation of kinase activity Source: UniProtKB
  • peptidyl-cysteine oxidation Source: ParkinsonsUK-UCL
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • regulation of mitochondrial membrane potential Source: UniProtKB
  • response to hydrogen peroxide Source: UniProtKB
  • response to lipopolysaccharide Source: UniProtKB
  • response to oxidative stress Source: UniProtKB

Keywordsi

Molecular functionAntioxidant, Oxidoreductase, Peroxidase

Enzyme and pathway databases

ReactomeiR-HSA-3299685. Detoxification of Reactive Oxygen Species.

Protein family/group databases

PeroxiBasei4492. Hs2CysPrx03.

Names & Taxonomyi

Protein namesi
Recommended name:
Thioredoxin-dependent peroxide reductase, mitochondrial (EC:1.11.1.152 Publications)
Alternative name(s):
Antioxidant protein 1
Short name:
AOP-1
HBC189
Peroxiredoxin III
Short name:
Prx-III
Peroxiredoxin-3
Protein MER5 homolog
Gene namesi
Name:PRDX3
Synonyms:AOP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000165672.6.
HGNCiHGNC:9354. PRDX3.

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, Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi146T → A: Impairs phosphorylation. 1 Publication1

Organism-specific databases

DisGeNETi10935.
OpenTargetsiENSG00000165672.
PharmGKBiPA33724.

Polymorphism and mutation databases

DMDMi2507171.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 61MitochondrionCombined sourcesAdd BLAST61
ChainiPRO_000002378262 – 256Thioredoxin-dependent peroxide reductase, mitochondrialAdd BLAST195

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei83N6-succinyllysineBy similarity1
Modified residuei91N6-acetyllysine; alternateCombined sources1
Modified residuei91N6-succinyllysine; alternateBy similarity1
Disulfide bondi108Interchain (with C-229); in linked formBy similarity
Modified residuei146Phosphothreonine1 Publication1
Disulfide bondi229Interchain (with C-108); in linked formBy similarity

Post-translational modificationi

Phosphorylated by LRRK2; phosphorylation reduces perodixase activity.1 Publication
The enzyme can be inactivated by further oxidation of the cysteine sulfenic acid (C(P)-SOH) to sulphinic acid (C(P)-SO2H) and sulphonic acid (C(P)-SO3H) instead of its condensation to a disulfide bond.1 Publication

Keywords - PTMi

Acetylation, Disulfide bond, Phosphoprotein

Proteomic databases

EPDiP30048.
MaxQBiP30048.
PaxDbiP30048.
PeptideAtlasiP30048.
PRIDEiP30048.
TopDownProteomicsiP30048-1. [P30048-1]

2D gel databases

OGPiP30048.
SWISS-2DPAGEiP30048.
UCD-2DPAGEiP30048.

PTM databases

iPTMnetiP30048.
PhosphoSitePlusiP30048.
SwissPalmiP30048.

Expressioni

Gene expression databases

BgeeiENSG00000165672.
CleanExiHS_PRDX3.
GenevisibleiP30048. HS.

Organism-specific databases

HPAiCAB008656.
HPA041488.

Interactioni

Subunit structurei

Homodimer; disulfide-linked, upon oxidation. 6 homodimers assemble to form a ring-like dodecamer (PubMed:17707404, PubMed:27238969). Interacts with NEK6 (PubMed:20873783). Interacts with LRRK2 (PubMed:21850687). Interacts with MAP3K13 (PubMed:12492477).5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • kinase binding Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116136. 67 interactors.
DIPiDIP-33600N.
IntActiP30048. 58 interactors.
MINTiMINT-195453.
STRINGi9606.ENSP00000298510.

Structurei

Secondary structure

1256
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi73 – 78Combined sources6
Beta strandi81 – 86Combined sources6
Helixi87 – 90Combined sources4
Beta strandi93 – 99Combined sources7
Helixi107 – 117Combined sources11
Helixi119 – 123Combined sources5
Turni124 – 126Combined sources3
Beta strandi127 – 135Combined sources9
Helixi137 – 144Combined sources8
Helixi148 – 150Combined sources3
Beta strandi157 – 162Combined sources6
Beta strandi164 – 166Combined sources3
Helixi167 – 171Combined sources5
Turni177 – 180Combined sources4
Beta strandi184 – 189Combined sources6
Beta strandi193 – 201Combined sources9
Helixi209 – 225Combined sources17
Turni244 – 247Combined sources4
Helixi248 – 253Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5JCGX-ray2.80A/B/C/D/E/F/G/H/I62-256[»]
ProteinModelPortaliP30048.
SMRiP30048.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini63 – 221ThioredoxinPROSITE-ProRule annotationAdd BLAST159

Sequence similaritiesi

Keywords - Domaini

Redox-active center, Transit peptide

Phylogenomic databases

eggNOGiKOG0852. Eukaryota.
COG0450. LUCA.
GeneTreeiENSGT00390000004653.
HOVERGENiHBG000286.
InParanoidiP30048.
KOiK20011.
OMAiTAVHNGE.
OrthoDBiEOG091G0IE5.
PhylomeDBiP30048.
TreeFamiTF105181.

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.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P30048-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAAVGRLLR ASVARHVSAI PWGISATAAL RPAACGRTSL TNLLCSGSSQ
60 70 80 90 100
AKLFSTSSSC HAPAVTQHAP YFKGTAVVNG EFKDLSLDDF KGKYLVLFFY
110 120 130 140 150
PLDFTFVCPT EIVAFSDKAN EFHDVNCEVV AVSVDSHFSH LAWINTPRKN
160 170 180 190 200
GGLGHMNIAL LSDLTKQISR DYGVLLEGSG LALRGLFIID PNGVIKHLSV
210 220 230 240 250
NDLPVGRSVE ETLRLVKAFQ YVETHGEVCP ANWTPDSPTI KPSPAASKEY

FQKVNQ
Length:256
Mass (Da):27,693
Last modified:November 1, 1997 - v3
Checksum:i8BEB7F5E55BFE9BE
GO
Isoform 2 (identifier: P30048-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     51-68: Missing.

Note: No experimental confirmation available. Gene prediction based on EST data.
Show »
Length:238
Mass (Da):25,839
Checksum:i28657F36943A2355
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti31R → W in AAH08435 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02505255S → R1 PublicationCorresponds to variant dbSNP:rs34698541Ensembl.1
Natural variantiVAR_059546170R → Q. Corresponds to variant dbSNP:rs11554902Ensembl.1
Natural variantiVAR_025053218A → T1 PublicationCorresponds to variant dbSNP:rs36064375Ensembl.1
Natural variantiVAR_025054234T → I1 PublicationCorresponds to variant dbSNP:rs35697338Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05405051 – 68Missing in isoform 2. CuratedAdd BLAST18

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D49396 mRNA. Translation: BAA08389.1.
AK313169 mRNA. Translation: BAG35987.1.
CR450344 mRNA. Translation: CAG29340.1.
BT020007 mRNA. Translation: AAV38810.1.
DQ298752 Genomic DNA. Translation: ABB84468.1.
AL355861 Genomic DNA. Translation: CAI15802.1.
CH471066 Genomic DNA. Translation: EAW49399.1.
BC002685 mRNA. Translation: AAH02685.1.
BC007062 mRNA. Translation: AAH07062.1.
BC008435 mRNA. Translation: AAH08435.1.
BC009601 mRNA. Translation: AAH09601.1.
BC021691 mRNA. Translation: AAH21691.1.
BC022373 mRNA. Translation: AAH22373.1.
BC059169 mRNA. Translation: AAH59169.1.
BC111397 mRNA. Translation: AAI11398.1.
CCDSiCCDS7611.1. [P30048-1]
RefSeqiNP_001289201.1. NM_001302272.1.
NP_006784.1. NM_006793.4. [P30048-1]
UniGeneiHs.523302.

Genome annotation databases

EnsembliENST00000298510; ENSP00000298510; ENSG00000165672. [P30048-1]
GeneIDi10935.
KEGGihsa:10935.
UCSCiuc001lec.5. human. [P30048-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPRDX3_HUMAN
AccessioniPrimary (citable) accession number: P30048
Secondary accession number(s): B2R7Z0
, D3DRC9, E9PH29, P35690, Q0D2H1, Q13776, Q5T5V2, Q96HK4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: November 1, 1997
Last modified: October 25, 2017
This is version 207 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

Caution

It is uncertain whether transit peptide cleavage occurs after His-61 or Ala-62. Peptides have been found for both N-termini.

Keywords - Technical termi

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

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families