ID PRDX3_MOUSE Reviewed; 257 AA.
AC P20108;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 27-MAR-2024, entry version 206.
DE RecName: Full=Thioredoxin-dependent peroxide reductase, mitochondrial;
DE EC=1.11.1.24 {ECO:0000269|PubMed:9497357};
DE AltName: Full=Antioxidant protein 1;
DE Short=AOP-1;
DE AltName: Full=PRX III;
DE AltName: Full=Perioredoxin-3;
DE AltName: Full=Protein MER5;
DE AltName: Full=Thioredoxin-dependent peroxiredoxin 3 {ECO:0000305};
DE Flags: Precursor;
GN Name=Prdx3; Synonyms=Aop1, Mer5;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2583515; DOI=10.1016/0378-1119(89)90297-7;
RA Yamamoto T., Matsui Y., Natori S., Obinata M.;
RT "Cloning of a housekeeping-type gene (MER5) preferentially expressed in
RT murine erythroleukemia cells.";
RL Gene 80:337-343(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RA Lee T.-H., Rhee S.G., Lee K.-K., Yu D.-Y.;
RT "Characterization of mouse peroxiredoxin III genomic DNA and its
RT expression.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 85-92; 151-167 AND 172-215, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain, and Hippocampus;
RA Lubec G., Kang S.U., Klug S., Yang J.W., Zigmond M.;
RL Submitted (JUL-2007) to UniProtKB.
RN [6]
RP CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=9497357; DOI=10.1074/jbc.273.11.6297;
RA Kang S.W., Chae H.Z., Seo M.S., Kim K., Baines I.C., Rhee S.G.;
RT "Mammalian peroxiredoxin isoforms can reduce hydrogen peroxide generated in
RT response to growth factors and tumor necrosis factor-alpha.";
RL J. Biol. Chem. 273:6297-6302(1998).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-84 AND LYS-92, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-92, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27037278; DOI=10.1177/1535370216642039;
RA Zhang Y.G., Wang L., Kaifu T., Li J., Li X., Li L.;
RT "Accelerated decline of physical strength in peroxiredoxin-3 knockout
RT mice.";
RL Exp. Biol. Med. (Maywood) 241:1395-1400(2016).
RN [11]
RP PALMITOYLATION.
RX PubMed=31740833; DOI=10.1038/s41589-019-0399-y;
RA Cao Y., Qiu T., Kathayat R.S., Azizi S.A., Thorne A.K., Ahn D., Fukata Y.,
RA Fukata M., Rice P.A., Dickinson B.C.;
RT "ABHD10 is an S-depalmitoylase affecting redox homeostasis through
RT peroxiredoxin-5.";
RL Nat. Chem. Biol. 15:1232-1240(2019).
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 (PubMed:27037278).
CC {ECO:0000250|UniProtKB:P30048, ECO:0000269|PubMed:27037278}.
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:0000269|PubMed:9497357};
CC -!- SUBUNIT: Homodimer; disulfide-linked, upon oxidation. 6 homodimers
CC assemble to form a ring-like dodecamer. Interacts with NEK6. Interacts
CC with LRRK2. Interacts with MAP3K13 (By similarity). Interacts with
CC RPS6KC1 (via PX domain). {ECO:0000250|UniProtKB:P30048}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:9497357}.
CC Cytoplasm {ECO:0000250|UniProtKB:P30048}. Early endosome
CC {ECO:0000250|UniProtKB:P30048}. Note=Localizes to early endosomes in a
CC RPS6KC1-dependent manner. {ECO:0000250|UniProtKB:P30048}.
CC -!- TISSUE SPECIFICITY: Housekeeping-type gene preferentially expressed in
CC murine erythroleukemia (MEL) cells.
CC -!- INDUCTION: Expression is increased after induction of MEL cells to
CC differentiation by DMSO.
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:0000269|PubMed:31740833}.
CC -!- DISRUPTION PHENOTYPE: Accelerates decline of physical strength; at the
CC age of 10 months, the physical strength is much lower than in the wild-
CC type littermate (PubMed:27037278). Increased oxidative damage and
CC decreased mitochondrial DNA copy number in skeletal muscles
CC (PubMed:27037278). Increased apoptotic cells in the brain
CC (PubMed:27037278). {ECO:0000269|PubMed:27037278}.
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:9497357}.
CC -!- SIMILARITY: Belongs to the peroxiredoxin family. AhpC/Prx1 subfamily.
CC {ECO:0000305}.
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DR EMBL; M28723; AAA39524.1; -; mRNA.
DR EMBL; AF211938; AAF63705.1; -; Genomic_DNA.
DR EMBL; AF211933; AAF63705.1; JOINED; Genomic_DNA.
DR EMBL; AF211934; AAF63705.1; JOINED; Genomic_DNA.
DR EMBL; AF211935; AAF63705.1; JOINED; Genomic_DNA.
DR EMBL; AF211936; AAF63705.1; JOINED; Genomic_DNA.
DR EMBL; AF211937; AAF63705.1; JOINED; Genomic_DNA.
DR EMBL; AK002448; BAB22108.1; -; mRNA.
DR EMBL; BC005626; AAH05626.1; -; mRNA.
DR CCDS; CCDS29944.1; -.
DR PIR; JQ0064; JQ0064.
DR RefSeq; NP_031478.1; NM_007452.2.
DR AlphaFoldDB; P20108; -.
DR SMR; P20108; -.
DR BioGRID; 198117; 13.
DR IntAct; P20108; 5.
DR MINT; P20108; -.
DR STRING; 10090.ENSMUSP00000025961; -.
DR PeroxiBase; 4499; Mm2CysPrx03.
DR GlyGen; P20108; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P20108; -.
DR PhosphoSitePlus; P20108; -.
DR SwissPalm; P20108; -.
DR REPRODUCTION-2DPAGE; IPI00116192; -.
DR REPRODUCTION-2DPAGE; P20108; -.
DR EPD; P20108; -.
DR jPOST; P20108; -.
DR MaxQB; P20108; -.
DR PaxDb; 10090-ENSMUSP00000025961; -.
DR PeptideAtlas; P20108; -.
DR ProteomicsDB; 291867; -.
DR Pumba; P20108; -.
DR TopDownProteomics; P20108; -.
DR Antibodypedia; 3274; 609 antibodies from 40 providers.
DR DNASU; 11757; -.
DR Ensembl; ENSMUST00000025961.7; ENSMUSP00000025961.7; ENSMUSG00000024997.8.
DR GeneID; 11757; -.
DR KEGG; mmu:11757; -.
DR UCSC; uc008icd.1; mouse.
DR AGR; MGI:88034; -.
DR CTD; 10935; -.
DR MGI; MGI:88034; Prdx3.
DR VEuPathDB; HostDB:ENSMUSG00000024997; -.
DR eggNOG; KOG0852; Eukaryota.
DR GeneTree; ENSGT00940000153430; -.
DR HOGENOM; CLU_042529_21_0_1; -.
DR InParanoid; P20108; -.
DR OMA; NNFGVMR; -.
DR OrthoDB; 47465at2759; -.
DR PhylomeDB; P20108; -.
DR TreeFam; TF105181; -.
DR Reactome; R-MMU-3299685; Detoxification of Reactive Oxygen Species.
DR BioGRID-ORCS; 11757; 3 hits in 79 CRISPR screens.
DR ChiTaRS; Prdx3; mouse.
DR PRO; PR:P20108; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; P20108; Protein.
DR Bgee; ENSMUSG00000024997; Expressed in adrenal gland and 266 other cell types or tissues.
DR Genevisible; P20108; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005769; C:early endosome; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0043209; C:myelin sheath; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0008379; F:thioredoxin peroxidase activity; ISO:MGI.
DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISO:MGI.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; ISO:MGI.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; ISO:MGI.
DR GO; GO:0001893; P:maternal placenta development; IMP:MGI.
DR GO; GO:0007005; P:mitochondrion organization; ISO:MGI.
DR GO; GO:0030099; P:myeloid cell differentiation; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; ISO:MGI.
DR GO; GO:0042542; P:response to hydrogen peroxide; ISO:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:MGI.
DR GO; GO:0006979; P:response to oxidative stress; IMP:MGI.
DR CDD; cd03015; PRX_Typ2cys; 1.
DR Gene3D; 3.40.30.10; Glutaredoxin; 1.
DR InterPro; IPR000866; AhpC/TSA.
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 Acetylation; Antioxidant; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; Endosome; Lipoprotein; Mitochondrion; Oxidoreductase;
KW Palmitate; Peroxidase; Phosphoprotein; Redox-active center;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..62
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P30048"
FT CHAIN 63..257
FT /note="Thioredoxin-dependent peroxide reductase,
FT mitochondrial"
FT /id="PRO_0000023783"
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:0000250|UniProtKB:P35705"
FT MOD_RES 84
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 92
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 92
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
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:0000250|UniProtKB:P35705"
FT DISULFID 230
FT /note="Interchain (with C-109); in linked form"
FT /evidence="ECO:0000250|UniProtKB:P35705"
SQ SEQUENCE 257 AA; 28127 MW; 66513F2C5F1D56C0 CRC64;
MAAAAGRLLW SSVARHASAI SRSISASTVL RPVASRRTCL TDILWSASAQ GKSAFSTSSS
FHTPAVTQHA PYFKGTAVVN GEFKELSLDD FKGKYLVLFF YPLDFTFVCP TEIVAFSDKA
NEFHDVNCEV VAVSVDSHFS HLAWINTPRK NGGLGHMNIT LLSDITKQIS RDYGVLLESA
GIALRGLFII DPNGVVKHLS VNDLPVGRSV EETLRLVKAF QFVETHGEVC PANWTPESPT
IKPSPTASKE YFEKVHQ
//
