ID PRDX3_BOVIN Reviewed; 257 AA. AC P35705; Q3SZA8; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 04-NOV-2026, entry version 171. DE RecName: Full=Thioredoxin-dependent peroxide reductase, mitochondrial; DE EC=1.11.1.24 {ECO:0000250|UniProtKB:P30048}; DE AltName: Full=Antioxidant protein 1; DE Short=AOP-1; DE AltName: Full=Peroxiredoxin-3; DE AltName: Full=Protein SP-22 {ECO:0000303|PubMed:8089078, ECO:0000303|PubMed:8912927}; DE AltName: Full=Thioredoxin-dependent peroxiredoxin 3 {ECO:0000305}; DE Flags: Precursor; GN Name=PRDX3; Synonyms=AOP1; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Adrenal medulla; RX PubMed=8912927; DOI=10.3109/10425179609008449; RA Hiroi T., Watabe S., Takimoto K., Yago N., Ymamoto Y., Takahashi S.Y.; RT "The cDNA sequence encoding bovine SP-22, a new defence system against RT reactive oxygen species in mitochondria."; RL DNA Seq. 6:239-242(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Crossbred X Angus; TISSUE=Ileum; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP PROTEIN SEQUENCE OF 63-257, CLEAVAGE OF TRANSIT PEPTIDE AFTER HIS-62, RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RC TISSUE=Adrenal medulla; RX PubMed=8089078; DOI=10.1093/oxfordjournals.jbchem.a124390; RA Watabe S., Kohno H., Kouyama H., Hiroi T., Yago N., Nakazawa T.; RT "Purification and characterization of a substrate protein for mitochondrial RT ATP-dependent protease in bovine adrenal cortex."; RL J. Biochem. 115:648-654(1994). RN [4] RP X-RAY CRYSTALLOGRAPHY OF MUTANT SER-230, AND SUBUNIT. RX PubMed=16271889; DOI=10.1016/j.str.2005.07.021; RA Cao Z., Roszak A.W., Gourlay L.J., Lindsay J.G., Isaacs N.W.; RT "Bovine mitochondrial peroxiredoxin III forms a two-ring catenane."; RL Structure 13:1661-1664(2005). RN [5] RP X-RAY CRYSTALLOGRAPHY, AND DISULFIDE BONDS. RX PubMed=25906064; DOI=10.1371/journal.pone.0123303; RA Cao Z., McGow D.P., Shepherd C., Lindsay J.G.; RT "Improved catenated structures of bovine peroxiredoxin III F190L reveal RT details of ring-ring interactions and a novel conformational state."; RL PLoS ONE 10:E0123303-E0123303(2015). CC -!- FUNCTION: Thiol-specific peroxidase that catalyzes the reduction of CC hydrogen peroxide and organic hydroperoxides to water and alcohols, CC respectively. Plays a role in cell protection against oxidative stress CC by detoxifying peroxides. Acts synergistically with MAP3K13 to regulate CC the activation of NF-kappa-B in the cytosol (By similarity). Required CC for the maintenance of physical strength (By similarity). CC {ECO:0000250|UniProtKB:P20108, ECO:0000250|UniProtKB:P30048}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a hydroperoxide + [thioredoxin]-dithiol = an alcohol + CC [thioredoxin]-disulfide + H2O; Xref=Rhea:RHEA:62620, Rhea:RHEA- CC COMP:10698, Rhea:RHEA-COMP:10700, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:29950, ChEBI:CHEBI:30879, ChEBI:CHEBI:35924, CC ChEBI:CHEBI:50058; EC=1.11.1.24; CC Evidence={ECO:0000250|UniProtKB:P30048}; CC -!- SUBUNIT: Homodimer; disulfide-linked, upon oxidation. 6 homodimers CC assemble to form a ring-like dodecamer (PubMed:16271889, CC PubMed:25906064). Interacts with NEK6 (By similarity). Interacts with CC LRRK2 (By similarity). Interacts with MAP3K13 (By similarity). CC Interacts with RPS6KC1 (via PX domain) (By similarity). CC {ECO:0000250|UniProtKB:P30048, ECO:0000269|PubMed:16271889, CC ECO:0000269|PubMed:25906064}. CC -!- INTERACTION: CC P35705; P35705: PRDX3; NbExp=4; IntAct=EBI-15559045, EBI-15559045; CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix CC {ECO:0000269|PubMed:8089078}. Cytoplasm {ECO:0000250|UniProtKB:P30048}. CC Early endosome {ECO:0000250|UniProtKB:P30048}. Note=Localizes to early CC endosomes in a RPS6KC1-dependent manner. CC {ECO:0000250|UniProtKB:P30048}. CC -!- TISSUE SPECIFICITY: Predominantly expressed in adrenal cortex. Also CC detected in liver, renal cortex and medulla, and adrenal medulla (at CC protein level). {ECO:0000269|PubMed:8089078}. CC -!- PTM: Phosphorylated by LRRK2; phosphorylation reduces perodixase CC activity. {ECO:0000250|UniProtKB:P30048}. CC -!- PTM: The enzyme can be inactivated by further oxidation of the cysteine CC sulfenic acid (C(P)-SOH) to sulphinic acid (C(P)-SO2H) and sulphonic CC acid (C(P)-SO3H) instead of its condensation to a disulfide bond. CC {ECO:0000250|UniProtKB:P30048}. CC -!- PTM: S-palmitoylated. {ECO:0000250|UniProtKB:P20108}. CC -!- MISCELLANEOUS: The active site is a conserved redox-active cysteine CC residue, the peroxidatic cysteine (C(P)), which makes the nucleophilic CC attack on the peroxide substrate. The peroxide oxidizes the C(P)-SH to CC cysteine sulfenic acid (C(P)-SOH), which then reacts with another CC cysteine residue, the resolving cysteine (C(R)), to form a disulfide CC bridge. The disulfide is subsequently reduced by an appropriate CC electron donor to complete the catalytic cycle. In this typical 2-Cys CC peroxiredoxin, C(R) is provided by the other dimeric subunit to form an CC intersubunit disulfide. The disulfide is subsequently reduced by CC thioredoxin. {ECO:0000305|PubMed:16271889}. CC -!- SIMILARITY: Belongs to the peroxiredoxin family. AhpC/Prx1 subfamily. CC {ECO:0000305}. CC -!- CAUTION: It is uncertain whether transit peptide cleavage occurs after CC His-62 or Ala-63. Peptides have been found for both N-termini in CC roughly equal amounts. {ECO:0000269|PubMed:8089078}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D82025; BAA11511.1; -; mRNA. DR EMBL; BC103009; AAI03010.1; -; mRNA. DR PIR; JC2258; JC2258. DR RefSeq; NP_776857.1; NM_174432.2. DR PDB; 1ZYE; X-ray; 3.30 A; A/B/C/D/E/F/G/H/I/J/K/L=63-257. DR PDB; 4MH2; X-ray; 2.20 A; A/B/C/D/E/F/G/H/I/J/K/L=63-257. DR PDB; 4MH3; X-ray; 2.40 A; A/B/C/D/E/F/G/H/I/J/K/L=63-257. DR AlphaFoldDB; P35705; -. DR SMR; P35705; -. DR DIP; DIP-48458N; -. DR FunCoup; P35705; 1304. DR STRING; 9913.ENSBTAP00000011505; -. DR PeroxiBase; 4502; Bt2CysPrx03. DR PaxDb; 9913-ENSBTAP00000011505; -. DR PeptideAtlas; P35705; -. DR Ensembl; ENSBTAT00000011505.3; ENSBTAP00000011505.1; ENSBTAG00000008731.4. DR Ensembl; ENSBTAT00085042712; ENSBTAP00085037651; ENSBTAG00085034247. DR Ensembl; ENSBTAT00090068821; ENSBTAP00090037832; ENSBTAG00090032524. DR GeneID; 281998; -. DR KEGG; bta:281998; -. DR CTD; 10935; -. DR VEuPathDB; HostDB:ENSBTAG00000008731; -. DR VGNC; VGNC:33301; PRDX3. DR eggNOG; KOG0852; Eukaryota. DR GeneTree; ENSGT00940000153430; -. DR HOGENOM; CLU_042529_21_0_1; -. DR InParanoid; P35705; -. DR OMA; AAACQHG; -. DR OrthoDB; 185659at2759; -. DR Reactome; R-BTA-3299685; Detoxification of Reactive Oxygen Species. DR EvolutionaryTrace; P35705; -. DR Proteomes; UP000009136; Chromosome 26. DR Bgee; ENSBTAG00000008731; Expressed in diaphragm and 102 other cell types or tissues. DR ExpressionAtlas; P35705; baseline. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005769; C:early endosome; ISS:UniProtKB. DR GO; GO:0005759; C:mitochondrial matrix; EXP:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central. DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl. DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl. DR GO; GO:0008379; F:thioredoxin peroxidase activity; IBA:GO_Central. DR GO; GO:0140824; F:thioredoxin-dependent peroxiredoxin activity; ISS:UniProtKB. DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central. DR GO; GO:0034614; P:cellular response to reactive oxygen species; IEA:Ensembl. DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IBA:GO_Central. DR GO; GO:0007005; P:mitochondrion organization; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IEA:Ensembl. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IEA:Ensembl. DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0006979; P:response to oxidative stress; IBA:GO_Central. DR CDD; cd03015; PRX_Typ2cys; 1. DR FunFam; 3.40.30.10:FF:000003; Peroxiredoxin 1; 1. DR Gene3D; 3.40.30.10; Glutaredoxin; 1. DR InterPro; IPR000866; AhpC/TSA. DR InterPro; IPR050217; Peroxiredoxin. DR InterPro; IPR019479; Peroxiredoxin_C. DR InterPro; IPR036249; Thioredoxin-like_sf. DR InterPro; IPR013766; Thioredoxin_domain. DR PANTHER; PTHR10681; THIOREDOXIN PEROXIDASE; 1. DR PANTHER; PTHR10681:SF128; THIOREDOXIN-DEPENDENT PEROXIDE REDUCTASE, MITOCHONDRIAL; 1. DR Pfam; PF10417; 1-cysPrx_C; 1. DR Pfam; PF00578; AhpC-TSA; 1. DR SUPFAM; SSF52833; Thioredoxin-like; 1. DR PROSITE; PS51352; THIOREDOXIN_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Antioxidant; Cytoplasm; KW Direct protein sequencing; Disulfide bond; Endosome; Lipoprotein; KW Mitochondrion; Oxidoreductase; Palmitate; Peroxidase; Phosphoprotein; KW Redox-active center; Reference proteome; Transit peptide. FT TRANSIT 1..62 FT /note="Mitochondrion" FT /evidence="ECO:0000269|PubMed:8089078" FT CHAIN 63..257 FT /note="Thioredoxin-dependent peroxide reductase, FT mitochondrial" FT /id="PRO_0000023781" FT DOMAIN 64..222 FT /note="Thioredoxin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691" FT ACT_SITE 109 FT /note="Cysteine sulfenic acid (-SOH) intermediate" FT /evidence="ECO:0000269|PubMed:8089078" FT MOD_RES 84 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P20108" FT MOD_RES 92 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P30048" FT MOD_RES 92 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P20108" FT MOD_RES 147 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P30048" FT DISULFID 109 FT /note="Interchain (with C-230); in linked form" FT /evidence="ECO:0000269|PubMed:16271889, FT ECO:0007744|PDB:4MH3" FT DISULFID 230 FT /note="Interchain (with C-109); in linked form" FT /evidence="ECO:0000269|PubMed:16271889, FT ECO:0007744|PDB:4MH3" FT STRAND 74..79 FT /evidence="ECO:0007829|PDB:4MH2" FT STRAND 82..87 FT /evidence="ECO:0007829|PDB:4MH2" FT HELIX 88..91 FT /evidence="ECO:0007829|PDB:4MH2" FT STRAND 94..100 FT /evidence="ECO:0007829|PDB:4MH2" FT STRAND 107..109 FT /evidence="ECO:0007829|PDB:4MH2" FT HELIX 110..118 FT /evidence="ECO:0007829|PDB:4MH2" FT HELIX 120..124 FT /evidence="ECO:0007829|PDB:4MH2" FT TURN 125..127 FT /evidence="ECO:0007829|PDB:4MH2" FT STRAND 128..136 FT /evidence="ECO:0007829|PDB:4MH2" FT HELIX 138..145 FT /evidence="ECO:0007829|PDB:4MH2" FT HELIX 149..151 FT /evidence="ECO:0007829|PDB:4MH2" FT STRAND 158..163 FT /evidence="ECO:0007829|PDB:4MH2" FT HELIX 168..172 FT /evidence="ECO:0007829|PDB:4MH2" FT TURN 178..181 FT /evidence="ECO:0007829|PDB:4MH2" FT STRAND 185..190 FT /evidence="ECO:0007829|PDB:4MH2" FT STRAND 194..202 FT /evidence="ECO:0007829|PDB:4MH2" FT HELIX 210..225 FT /evidence="ECO:0007829|PDB:4MH2" SQ SEQUENCE 257 AA; 28195 MW; F2E89EE2F172A42D CRC64; MAATAGRLFR ASLIRHVSAI PWGISASAAL RPAASRRMCL TNALWSGSDQ AKFAFSTSSS YHAPAVTQHA PYFKGTAVVS GEFKEISLDD FKGKYLVLFF YPLDFTFVCP TEIIAFSDKA SEFHDVNCEV VAVSVDSHFS HLAWINTPRK NGGLGHMNIA LLSDLTKQIS RDYGVLLEGP GLALRGLFII DPNGVIKHLS VNDLPVGRSV EETLRLVKAF QFVEAHGEVC PANWTPESPT IKPHPTASRE YFEKVNQ //