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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

Involved in redox regulation of the cell. Protects radical-sensitive enzymes from oxidative damage by a radical-generating system. Acts synergistically with MAP3K13 to regulate the activation of NF-kappa-B in the cytosol.1 Publication

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei108 – 1081Cysteine sulfenic acid (-SOH) intermediateBy similarity

GO - Molecular functioni

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

GO - Biological processi

  • cellular response to oxidative stress Source: ParkinsonsUK-UCL
  • cellular response to reactive oxygen species Source: UniProtKB
  • hydrogen peroxide catabolic process Source: UniProtKB
  • maternal placenta development Source: Ensembl
  • mitochondrion organization Source: UniProtKB
  • myeloid cell differentiation Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • 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
  • response to reactive oxygen species Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Antioxidant, 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:1.11.1.15)
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

HGNCiHGNC:9354. PRDX3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: ParkinsonsUK-UCL
  • early endosome Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • mitochondrial matrix Source: Reactome
  • mitochondrion Source: UniProtKB
  • myelin sheath Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi146 – 1461T → A: Impairs phosphorylation. 1 Publication

Organism-specific databases

PharmGKBiPA33724.

Polymorphism and mutation databases

DMDMi2507171.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 6161MitochondrionCombined sourcesAdd
BLAST
Chaini62 – 256195Thioredoxin-dependent peroxide reductase, mitochondrialPRO_0000023782Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei83 – 831N6-succinyllysineBy similarity
Modified residuei91 – 911N6-acetyllysine; alternateCombined sources
Modified residuei91 – 911N6-succinyllysine; alternateBy similarity
Disulfide bondi108 – 108Interchain (with C-229); in linked formBy similarity
Modified residuei146 – 1461Phosphothreonine1 Publication
Disulfide bondi229 – 229Interchain (with C-108); in linked formBy similarity

Post-translational modificationi

Phosphorylated by LRRK2; phosphorylation reduces perodixase activity.1 Publication

Keywords - PTMi

Acetylation, Disulfide bond, Phosphoprotein

Proteomic databases

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

2D gel databases

OGPiP30048.
SWISS-2DPAGEP30048.
UCD-2DPAGEP30048.

PTM databases

iPTMnetiP30048.
PhosphoSiteiP30048.
SwissPalmiP30048.

Expressioni

Gene expression databases

BgeeiENSG00000165672.
CleanExiHS_PRDX3.
GenevisibleiP30048. HS.

Organism-specific databases

HPAiCAB008656.
HPA041488.

Interactioni

Subunit structurei

Dodecameric ring assembled from homodimeric units; disulfide-linked, upon oxidation. The rings have an approximate diameter of 150 A and a central hole of 70 A. 3-5% of the rings are interlocked by pairs. Binds MAP3K13. Interacts with NEK6. Interacts with LRRK2.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GORASP2Q9H8Y83EBI-748336,EBI-739467
LRRK2Q5S00712EBI-748336,EBI-5323863

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi116136. 63 interactions.
DIPiDIP-33600N.
IntActiP30048. 54 interactions.
MINTiMINT-195453.
STRINGi9606.ENSP00000298510.

Structurei

Secondary structure

1
256
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi73 – 786Combined sources
Beta strandi81 – 866Combined sources
Helixi87 – 904Combined sources
Beta strandi93 – 997Combined sources
Helixi107 – 11711Combined sources
Helixi119 – 1235Combined sources
Turni124 – 1263Combined sources
Beta strandi127 – 1359Combined sources
Helixi137 – 1448Combined sources
Helixi148 – 1503Combined sources
Beta strandi157 – 1626Combined sources
Beta strandi164 – 1663Combined sources
Helixi167 – 1715Combined sources
Turni177 – 1804Combined sources
Beta strandi184 – 1896Combined sources
Beta strandi193 – 2019Combined sources
Helixi209 – 22517Combined sources
Turni244 – 2474Combined sources
Helixi248 – 2536Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
5JCGX-ray2.80A/B/C/D/E/F/G/H/I62-256[»]
ProteinModelPortaliP30048.
SMRiP30048. Positions 62-256.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini63 – 221159ThioredoxinPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the AhpC/TSA family.Curated
Contains 1 thioredoxin domain.PROSITE-ProRule annotation

Keywords - Domaini

Redox-active center, Transit peptide

Phylogenomic databases

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

Family and domain databases

Gene3Di3.40.30.10. 1 hit.
InterProiIPR000866. AhpC/TSA.
IPR019479. Peroxiredoxin_C.
IPR012336. Thioredoxin-like_fold.
IPR013766. Thioredoxin_domain.
[Graphical view]
PfamiPF10417. 1-cysPrx_C. 1 hit.
PF00578. AhpC-TSA. 1 hit.
[Graphical view]
SUPFAMiSSF52833. SSF52833. 1 hit.
PROSITEiPS51352. THIOREDOXIN_2. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti31 – 311R → W in AAH08435 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti55 – 551S → R.1 Publication
Corresponds to variant rs34698541 [ dbSNP | Ensembl ].
VAR_025052
Natural varianti170 – 1701R → Q.
Corresponds to variant rs11554902 [ dbSNP | Ensembl ].
VAR_059546
Natural varianti218 – 2181A → T.1 Publication
Corresponds to variant rs36064375 [ dbSNP | Ensembl ].
VAR_025053
Natural varianti234 – 2341T → I.1 Publication
Corresponds to variant rs35697338 [ dbSNP | Ensembl ].
VAR_025054

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei51 – 6818Missing in isoform 2. CuratedVSP_054050Add
BLAST

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

Cross-referencesi

Web resourcesi

NIEHS-SNPs

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
5JCGX-ray2.80A/B/C/D/E/F/G/H/I62-256[»]
ProteinModelPortaliP30048.
SMRiP30048. Positions 62-256.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116136. 63 interactions.
DIPiDIP-33600N.
IntActiP30048. 54 interactions.
MINTiMINT-195453.
STRINGi9606.ENSP00000298510.

Protein family/group databases

PeroxiBasei4492. Hs2CysPrx03.

PTM databases

iPTMnetiP30048.
PhosphoSiteiP30048.
SwissPalmiP30048.

Polymorphism and mutation databases

DMDMi2507171.

2D gel databases

OGPiP30048.
SWISS-2DPAGEP30048.
UCD-2DPAGEP30048.

Proteomic databases

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

Protocols and materials databases

DNASUi10935.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi10935.
GeneCardsiPRDX3.
H-InvDBHIX0035477.
HGNCiHGNC:9354. PRDX3.
HPAiCAB008656.
HPA041488.
MIMi604769. gene.
neXtProtiNX_P30048.
PharmGKBiPA33724.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiPRDX3. human.
GeneWikiiPRDX3.
GenomeRNAii10935.
PROiP30048.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165672.
CleanExiHS_PRDX3.
GenevisibleiP30048. HS.

Family and domain databases

Gene3Di3.40.30.10. 1 hit.
InterProiIPR000866. AhpC/TSA.
IPR019479. Peroxiredoxin_C.
IPR012336. Thioredoxin-like_fold.
IPR013766. Thioredoxin_domain.
[Graphical view]
PfamiPF10417. 1-cysPrx_C. 1 hit.
PF00578. AhpC-TSA. 1 hit.
[Graphical view]
SUPFAMiSSF52833. SSF52833. 1 hit.
PROSITEiPS51352. THIOREDOXIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPRDX3_HUMAN
AccessioniPrimary (citable) accession number: P30048
Secondary accession number(s): B2R7Z0
, D3DRC9, E9PH29, P35690, Q0D2H1, Q13776, Q5T5V2, Q96HK4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: November 1, 1997
Last modified: September 7, 2016
This is version 196 of the entry and version 3 of the sequence. [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

Miscellaneous

The active site is the redox-active Cys-108 oxidized to Cys-SOH. Cys-SOH rapidly reacts with Cys-229-SH of the other subunit to form an intermolecular disulfide with a concomitant homodimer formation. The enzyme may be subsequently regenerated by reduction of the disulfide by thioredoxin.
Irreversibly inactivated by overoxidation of Cys-108 (to Cys-SO3H) upon oxidative stress.

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.