PRDX3_BOVIN
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 03-AUG-2022, entry version 154.
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 (3.3 ANGSTROMS) OF 63-257 OF MUTANT SER-230, AND
RP 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 (2.20 ANGSTROMS), 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. {ECO:0000250|UniProtKB:P30048}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thioredoxin]-dithiol + a hydroperoxide = [thioredoxin]-
CC disulfide + an alcohol + 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 RPS6KC1 (via PX domain) (By
CC similarity). {ECO:0000250|UniProtKB:P30048,
CC ECO:0000269|PubMed:16271889, 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}.
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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 PDBsum; 1ZYE; -.
DR PDBsum; 4MH2; -.
DR PDBsum; 4MH3; -.
DR AlphaFoldDB; P35705; -.
DR SMR; P35705; -.
DR DIP; DIP-48458N; -.
DR STRING; 9913.ENSBTAP00000011505; -.
DR PeroxiBase; 4502; Bt2CysPrx03.
DR PaxDb; P35705; -.
DR PeptideAtlas; P35705; -.
DR PRIDE; P35705; -.
DR Ensembl; ENSBTAT00000011505; ENSBTAP00000011505; ENSBTAG00000008731.
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; WWPKDFT; -.
DR OrthoDB; 1326484at2759; -.
DR TreeFam; TF105181; -.
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 tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
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:0008022; F:protein C-terminus binding; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0008379; F:thioredoxin peroxidase activity; IBA:GO_Central.
DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central.
DR GO; GO:0034599; P:cellular response to oxidative stress; 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; IEA:Ensembl.
DR GO; GO:0001893; P:maternal placenta development; IEA:Ensembl.
DR GO; GO:0007005; P:mitochondrion organization; IEA:Ensembl.
DR GO; GO:0030099; P:myeloid cell differentiation; IEA:Ensembl.
DR GO; GO:0033673; P:negative regulation of kinase activity; IEA:Ensembl.
DR GO; GO:0018171; P:peptidyl-cysteine oxidation; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; 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:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR InterPro; IPR000866; AhpC/TSA.
DR InterPro; IPR019479; Peroxiredoxin_C.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR013766; Thioredoxin_domain.
DR Pfam; PF10417; 1-cysPrx_C; 1.
DR Pfam; PF00578; AhpC-TSA; 1.
DR SUPFAM; SSF52833; SSF52833; 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
