ID PRDX3_HUMAN Reviewed; 256 AA. AC P30048; B2R7Z0; D3DRC9; E9PH29; P35690; Q0D2H1; Q13776; Q5T5V2; Q96HK4; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 3. DT 27-MAR-2024, entry version 248. DE RecName: Full=Thioredoxin-dependent peroxide reductase, mitochondrial; DE EC=1.11.1.24 {ECO:0000269|PubMed:17707404, ECO:0000269|PubMed:19462976}; DE AltName: Full=Antioxidant protein 1; DE Short=AOP-1; DE AltName: Full=HBC189; DE AltName: Full=Peroxiredoxin III; DE Short=Prx-III; DE AltName: Full=Peroxiredoxin-3; DE AltName: Full=Protein MER5 homolog; DE AltName: Full=Thioredoxin-dependent peroxiredoxin 3 {ECO:0000305}; DE Flags: Precursor; GN Name=PRDX3; Synonyms=AOP1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION. RC TISSUE=Blood; RX PubMed=7733872; DOI=10.1042/bj3070377; RA Tsuji K., Copeland N.G., Jenkins N.A., Obinata M.; RT "Mammalian antioxidant protein complements alkylhydroperoxide reductase RT (ahpC) mutation in Escherichia coli."; RL Biochem. J. 307:377-381(1995). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-55; THR-218 AND RP ILE-234. RG NIEHS SNPs program; RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Bone marrow, Skeletal muscle, Testis, Urinary bladder, and RC Uterus; 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 [9] RP PROTEIN SEQUENCE OF 63-72 (ISOFORM 1). RC TISSUE=Liver; RX PubMed=1286669; DOI=10.1002/elps.11501301201; RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F., RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R., RA Appel R.D., Hughes G.J.; RT "Human liver protein map: a reference database established by RT microsequencing and gel comparison."; RL Electrophoresis 13:992-1001(1992). RN [10] RP PROTEIN SEQUENCE OF 74-93; 149-166 AND 171-214 (ISOFORM 1), AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex; RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.; RL Submitted (DEC-2008) to UniProtKB. RN [11] RP OVEROXIDATION AT CYS-108. RX PubMed=12059788; DOI=10.1042/bj20020525; RA Wagner E., Luche S., Penna L., Chevallet M., van Dorsselaer A., RA Leize-Wagner E., Rabilloud T.; RT "A method for detection of overoxidation of cysteines: peroxiredoxins are RT oxidized in vivo at the active-site cysteine during oxidative stress."; RL Biochem. J. 366:777-785(2002). RN [12] RP FUNCTION, AND INTERACTION WITH MAP3K13. RX PubMed=12492477; DOI=10.1046/j.1432-1033.2003.03363.x; RA Masaki M., Ikeda A., Shiraki E., Oka S., Kawasaki T.; RT "Mixed lineage kinase LZK and antioxidant protein-1 activate NF-kappaB RT synergistically."; RL Eur. J. Biochem. 270:76-83(2003). RN [13] RP INTERACTION WITH RPS6KC1, AND SUBCELLULAR LOCATION. RX PubMed=15750338; RA Liu L., Yang C., Yuan J., Chen X., Xu J., Wei Y., Yang J., Lin G., Yu L.; RT "RPK118, a PX domain-containing protein, interacts with peroxiredoxin-3 RT through pseudo-kinase domains."; RL Mol. Cells 19:39-45(2005). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT. RX PubMed=17707404; DOI=10.1016/j.jmb.2007.07.018; RA Cao Z., Bhella D., Lindsay J.G.; RT "Reconstitution of the mitochondrial PrxIII antioxidant defence pathway: RT general properties and factors affecting PrxIII activity and oligomeric RT state."; RL J. Mol. Biol. 372:1022-1033(2007). RN [15] RP CATALYTIC ACTIVITY. RX PubMed=19462976; DOI=10.1021/bi900558g; RA Cox A.G., Peskin A.V., Paton L.N., Winterbourn C.C., Hampton M.B.; RT "Redox potential and peroxide reactivity of human peroxiredoxin 3."; RL Biochemistry 48:6495-6501(2009). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-91, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [17] RP INTERACTION WITH NEK6. RX PubMed=20873783; DOI=10.1021/pr100562w; RA Vaz Meirelles G., Ferreira Lanza D.C., da Silva J.C., Santana Bernachi J., RA Paes Leme A.F., Kobarg J.; RT "Characterization of hNek6 interactome reveals an important role for its RT short N-terminal domain and colocalization with proteins at the RT centrosome."; RL J. Proteome Res. 9:6298-6316(2010). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP INTERACTION WITH LRRK2, PHOSPHORYLATION AT THR-146, AND MUTAGENESIS OF RP THR-146. RX PubMed=21850687; DOI=10.1002/humu.21582; RA Angeles D.C., Gan B.H., Onstead L., Zhao Y., Lim K.L., Dachsel J., RA Melrose H., Farrer M., Wszolek Z.K., Dickson D.W., Tan E.K.; RT "Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 RT exacerbating oxidative stress-induced neuronal death."; RL Hum. Mutat. 32:1390-1397(2011). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [21] RP CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER HIS-61, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS), AND SUBUNIT. RX PubMed=27238969; DOI=10.1016/j.str.2016.04.013; RA Yewdall N.A., Venugopal H., Desfosses A., Abrishami V., Yosaatmadja Y., RA Hampton M.B., Gerrard J.A., Goldstone D.C., Mitra A.K., Radjainia M.; RT "Structures of human peroxiredoxin 3 suggest self-chaperoning assembly that RT maintains catalytic state."; RL Structure 24:1120-1129(2016). RN [23] {ECO:0007744|PDB:5UCX} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 62-256 OF MUTANT CYS-139, RP FUNCTION, SUBUNIT, AND MUTAGENESIS OF SER-136 AND SER-139. RX PubMed=29438714; DOI=10.1016/j.bbrc.2018.02.093; RA Yewdall N.A., Peskin A.V., Hampton M.B., Goldstone D.C., Pearce F.G., RA Gerrard J.A.; RT "Quaternary structure influences the peroxidase activity of peroxiredoxin RT 3."; RL Biochem. Biophys. Res. Commun. 497:558-563(2018). RN [24] RP INVOLVEMENT IN PPPCD, AND VARIANT PPPCD HIS-190. RX PubMed=31782998; DOI=10.1016/j.ajo.2019.11.024; RA Alio Del Barrio J.L., Chung D.D., Al-Shymali O., Barrington A., RA Jatavallabhula K., Swamy V.S., Yebana P., Angelica Henriquez-Recine M., RA Boto-de-Los-Bueis A., Alio J.L., Aldave A.J.; RT "Punctiform and Polychromatic Pre-Descemet Corneal Dystrophy: Clinical RT Evaluation and Identification of the Genetic Basis."; RL Am. J. Ophthalmol. 212:88-97(2020). RN [25] RP INVOLVEMENT IN SCAR32, VARIANTS SCAR32 GLY-142; 170-ARG--GLN-256 DEL AND RP ASN-202, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=33889951; DOI=10.1093/brain/awab071; RG PREPARE network; RA Rebelo A.P., Eidhof I., Cintra V.P., Guillot-Noel L., Pereira C.V., RA Timmann D., Traschuetz A., Schoels L., Coarelli G., Durr A., Anheim M., RA Tranchant C., van de Warrenburg B., Guissart C., Koenig M., Howell J., RA Moraes C.T., Schenck A., Stevanin G., Zuechner S., Synofzik M.; RT "Biallelic loss-of-function variations in PRDX3 cause cerebellar ataxia."; RL Brain 144:1467-1481(2021). RN [26] RP VARIANT PPPCD HIS-190. RX PubMed=34369396; DOI=10.1097/ico.0000000000002828; RA Choo C.H., Boto de Los Bueis A., Chung D.D., Aldave A.J.; RT "Confirmation of PRDX3 c.568G>C as the Genetic Basis of Punctiform and RT Polychromatic Pre-Descemet Corneal Dystrophy."; RL Cornea 41:779-781(2022). 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 (PubMed:7733872, PubMed:17707404, CC PubMed:29438714, PubMed:33889951). Acts synergistically with MAP3K13 to CC regulate the activation of NF-kappa-B in the cytosol (PubMed:12492477). CC Required for the maintenance of physical strength (By similarity). CC {ECO:0000250|UniProtKB:P20108, ECO:0000269|PubMed:12492477, CC ECO:0000269|PubMed:17707404, ECO:0000269|PubMed:29438714, CC ECO:0000269|PubMed:33889951, ECO:0000269|PubMed:7733872}. 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:17707404, ECO:0000269|PubMed:19462976}; CC -!- SUBUNIT: Homodimer; disulfide-linked, upon oxidation (PubMed:17707404, CC PubMed:27238969, PubMed:29438714). 6 homodimers assemble to form a CC ring-like dodecamer (PubMed:17707404, PubMed:27238969, CC PubMed:29438714). Interacts with NEK6 (PubMed:20873783). Interacts with CC LRRK2 (PubMed:21850687). Interacts with MAP3K13 (PubMed:12492477). CC Interacts with RPS6KC1 (via PX domain) (PubMed:15750338). CC {ECO:0000269|PubMed:12492477, ECO:0000269|PubMed:15750338, CC ECO:0000269|PubMed:17707404, ECO:0000269|PubMed:20873783, CC ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:27238969, CC ECO:0000269|PubMed:29438714}. CC -!- INTERACTION: CC P30048; Q9H8Y8: GORASP2; NbExp=6; IntAct=EBI-748336, EBI-739467; CC P30048; Q5S007: LRRK2; NbExp=14; IntAct=EBI-748336, EBI-5323863; CC P30048; P30048: PRDX3; NbExp=2; IntAct=EBI-748336, EBI-748336; CC P30048; Q15935: ZNF77; NbExp=3; IntAct=EBI-748336, EBI-12840750; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:33889951}. CC Cytoplasm {ECO:0000305|PubMed:12492477}. Early endosome CC {ECO:0000269|PubMed:15750338}. Note=Localizes to early endosomes in a CC RPS6KC1-dependent manner. {ECO:0000269|PubMed:15750338}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P30048-1; Sequence=Displayed; CC Name=2; CC IsoId=P30048-2; Sequence=VSP_054050; CC -!- PTM: Phosphorylated by LRRK2; phosphorylation reduces perodixase CC activity. {ECO:0000269|PubMed:21850687}. 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:0000269|PubMed:12059788}. CC -!- PTM: S-palmitoylated. {ECO:0000250|UniProtKB:P20108}. CC -!- DISEASE: Spinocerebellar ataxia, autosomal recessive, 32 (SCAR32) CC [MIM:619862]: A form of spinocerebellar ataxia, a clinically and CC genetically heterogeneous group of cerebellar disorders due to CC degeneration of the cerebellum with variable involvement of the CC brainstem and spinal cord. SCAR32 is characterized by the onset of gait CC ataxia in the second or third decades of life. Other classic features CC include upper limb ataxia, oculomotor signs, dysphagia, and dysarthria. CC Some patients may have hyper- or hypokinetic movement abnormalities. CC Brain imaging shows cerebellar atrophy. Atrophy can extend to the CC brainstem and medullary olives. {ECO:0000269|PubMed:33889951}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Corneal dystrophy, punctiform and polychromatic pre-Descemet CC (PPPCD) [MIM:619871]: An autosomal dominant corneal dystrophy CC characterized by the presence of punctiform, multicolored opacities in CC the posterior stroma, immediately anterior to Descemet membrane. CC Affected individuals are typically asymptomatic. CC {ECO:0000269|PubMed:31782998, ECO:0000269|PubMed:34369396}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. 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:17707404}. 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-61 or Ala-62. Peptides have been found for both N-termini. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/prdx3/"; 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; D49396; BAA08389.1; -; mRNA. DR EMBL; AK313169; BAG35987.1; -; mRNA. DR EMBL; CR450344; CAG29340.1; -; mRNA. DR EMBL; BT020007; AAV38810.1; -; mRNA. DR EMBL; DQ298752; ABB84468.1; -; Genomic_DNA. DR EMBL; AL355861; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471066; EAW49399.1; -; Genomic_DNA. DR EMBL; BC002685; AAH02685.1; -; mRNA. DR EMBL; BC007062; AAH07062.1; -; mRNA. DR EMBL; BC008435; AAH08435.1; -; mRNA. DR EMBL; BC009601; AAH09601.1; -; mRNA. DR EMBL; BC021691; AAH21691.1; -; mRNA. DR EMBL; BC022373; AAH22373.1; -; mRNA. DR EMBL; BC059169; AAH59169.1; -; mRNA. DR EMBL; BC111397; AAI11398.1; -; mRNA. DR CCDS; CCDS7611.1; -. [P30048-1] DR RefSeq; NP_001289201.1; NM_001302272.1. DR RefSeq; NP_006784.1; NM_006793.4. [P30048-1] DR PDB; 5JCG; X-ray; 2.80 A; A/B/C/D/E/F/G/H/I=62-256. DR PDB; 5UCX; X-ray; 2.40 A; A/B/C/D/E/F/G/H/I=62-256. DR PDBsum; 5JCG; -. DR PDBsum; 5UCX; -. DR AlphaFoldDB; P30048; -. DR EMDB; EMD-6309; -. DR SMR; P30048; -. DR BioGRID; 116136; 300. DR DIP; DIP-33600N; -. DR IntAct; P30048; 111. DR MINT; P30048; -. DR STRING; 9606.ENSP00000298510; -. DR ChEMBL; CHEMBL4295742; -. DR PeroxiBase; 4492; Hs2CysPrx03. DR GlyGen; P30048; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P30048; -. DR PhosphoSitePlus; P30048; -. DR SwissPalm; P30048; -. DR BioMuta; PRDX3; -. DR DMDM; 2507171; -. DR OGP; P30048; -. DR CPTAC; CPTAC-115; -. DR CPTAC; CPTAC-116; -. DR EPD; P30048; -. DR jPOST; P30048; -. DR MassIVE; P30048; -. DR MaxQB; P30048; -. DR PaxDb; 9606-ENSP00000298510; -. DR PeptideAtlas; P30048; -. DR ProteomicsDB; 20445; -. DR ProteomicsDB; 54628; -. [P30048-1] DR Pumba; P30048; -. DR TopDownProteomics; P30048-1; -. [P30048-1] DR Antibodypedia; 3274; 609 antibodies from 40 providers. DR DNASU; 10935; -. DR Ensembl; ENST00000298510.4; ENSP00000298510.2; ENSG00000165672.7. [P30048-1] DR GeneID; 10935; -. DR KEGG; hsa:10935; -. DR MANE-Select; ENST00000298510.4; ENSP00000298510.2; NM_006793.5; NP_006784.1. DR UCSC; uc001lec.5; human. [P30048-1] DR AGR; HGNC:9354; -. DR CTD; 10935; -. DR DisGeNET; 10935; -. DR GeneCards; PRDX3; -. DR HGNC; HGNC:9354; PRDX3. DR HPA; ENSG00000165672; Low tissue specificity. DR MalaCards; PRDX3; -. DR MIM; 604769; gene. DR MIM; 619862; phenotype. DR MIM; 619871; phenotype. DR neXtProt; NX_P30048; -. DR OpenTargets; ENSG00000165672; -. DR PharmGKB; PA33724; -. DR VEuPathDB; HostDB:ENSG00000165672; -. DR eggNOG; KOG0852; Eukaryota. DR GeneTree; ENSGT00940000153430; -. DR HOGENOM; CLU_042529_21_0_1; -. DR InParanoid; P30048; -. DR OMA; NNFGVMR; -. DR OrthoDB; 47465at2759; -. DR PhylomeDB; P30048; -. DR TreeFam; TF105181; -. DR PathwayCommons; P30048; -. DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species. DR SignaLink; P30048; -. DR SIGNOR; P30048; -. DR BioGRID-ORCS; 10935; 88 hits in 1155 CRISPR screens. DR ChiTaRS; PRDX3; human. DR GeneWiki; PRDX3; -. DR GenomeRNAi; 10935; -. DR Pharos; P30048; Tbio. DR PRO; PR:P30048; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; P30048; Protein. DR Bgee; ENSG00000165672; Expressed in adrenal tissue and 212 other cell types or tissues. DR ExpressionAtlas; P30048; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:ParkinsonsUK-UCL. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0008785; F:alkyl hydroperoxide reductase activity; NAS:UniProtKB. DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IMP:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0019901; F:protein kinase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0008379; F:thioredoxin peroxidase activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central. DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:ParkinsonsUK-UCL. DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:UniProtKB. DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IDA:MGI. DR GO; GO:0001893; P:maternal placenta development; IEA:Ensembl. DR GO; GO:0007005; P:mitochondrion organization; IMP:UniProtKB. DR GO; GO:0030099; P:myeloid cell differentiation; ISS:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:ParkinsonsUK-UCL. DR GO; GO:0033673; P:negative regulation of kinase activity; IDA:UniProtKB. DR GO; GO:0018171; P:peptidyl-cysteine oxidation; IDA:ParkinsonsUK-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB. DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IMP:UniProtKB. DR GO; GO:0042542; P:response to hydrogen peroxide; IDA:UniProtKB. DR GO; GO:0032496; P:response to lipopolysaccharide; ISS:UniProtKB. DR GO; GO:0006979; P:response to oxidative stress; IMP:UniProtKB. 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. DR SWISS-2DPAGE; P30048; -. DR UCD-2DPAGE; P30048; -. DR Genevisible; P30048; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Antioxidant; KW Corneal dystrophy; Cytoplasm; Direct protein sequencing; Disease variant; KW Disulfide bond; Endosome; Lipoprotein; Mitochondrion; Neurodegeneration; KW Oxidoreductase; Palmitate; Peroxidase; Phosphoprotein; Redox-active center; KW Reference proteome; Transit peptide. FT TRANSIT 1..61 FT /note="Mitochondrion" FT /evidence="ECO:0007744|PubMed:25944712" FT CHAIN 62..256 FT /note="Thioredoxin-dependent peroxide reductase, FT mitochondrial" FT /id="PRO_0000023782" FT DOMAIN 63..221 FT /note="Thioredoxin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691" FT ACT_SITE 108 FT /note="Cysteine sulfenic acid (-SOH) intermediate" FT /evidence="ECO:0000250|UniProtKB:P35705" FT MOD_RES 83 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P20108" FT MOD_RES 91 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 91 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P20108" FT MOD_RES 146 FT /note="Phosphothreonine" FT /evidence="ECO:0000305|PubMed:21850687" FT DISULFID 108 FT /note="Interchain (with C-229); in linked form" FT /evidence="ECO:0000250|UniProtKB:P35705" FT DISULFID 229 FT /note="Interchain (with C-108); in linked form" FT /evidence="ECO:0000250|UniProtKB:P35705" FT VAR_SEQ 51..68 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_054050" FT VARIANT 55 FT /note="S -> R (in dbSNP:rs34698541)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_025052" FT VARIANT 142 FT /note="A -> G (in SCAR32; uncertain significance; FT dbSNP:rs202061531)" FT /evidence="ECO:0000269|PubMed:33889951" FT /id="VAR_087329" FT VARIANT 170..256 FT /note="Missing (in SCAR32; absent protein, reduced FT glutathione peroxidase activity and reduced PRDX5 protein FT levels in patient fibroblasts; dbSNP:rs140609531)" FT /evidence="ECO:0000269|PubMed:33889951" FT /id="VAR_087330" FT VARIANT 170 FT /note="R -> Q (in dbSNP:rs11554902)" FT /id="VAR_059546" FT VARIANT 190 FT /note="D -> H (in PPPCD)" FT /evidence="ECO:0000269|PubMed:31782998, FT ECO:0000269|PubMed:34369396" FT /id="VAR_087331" FT VARIANT 202 FT /note="D -> N (in SCAR32; unstable protein leading to its FT degradation, reduced glutathione peroxidase activity and FT reduced PRDX5 protein levels in patient fibroblasts; FT dbSNP:rs548327727)" FT /evidence="ECO:0000269|PubMed:33889951" FT /id="VAR_087332" FT VARIANT 218 FT /note="A -> T (in dbSNP:rs36064375)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_025053" FT VARIANT 234 FT /note="T -> I (in dbSNP:rs35697338)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_025054" FT MUTAGEN 136 FT /note="S->E: Forms obligate homodimers under reducing and FT oxidizing conditions; does not form dodecamer rings under FT reducing conditions." FT /evidence="ECO:0000269|PubMed:29438714" FT MUTAGEN 139 FT /note="S->C: Forms predominantly dodecamer rings." FT /evidence="ECO:0000269|PubMed:29438714" FT MUTAGEN 146 FT /note="T->A: Impairs phosphorylation." FT /evidence="ECO:0000269|PubMed:21850687" FT CONFLICT 31 FT /note="R -> W (in Ref. 8; AAH08435)" FT /evidence="ECO:0000305" FT STRAND 73..78 FT /evidence="ECO:0007829|PDB:5UCX" FT STRAND 81..86 FT /evidence="ECO:0007829|PDB:5UCX" FT HELIX 87..90 FT /evidence="ECO:0007829|PDB:5UCX" FT STRAND 93..99 FT /evidence="ECO:0007829|PDB:5UCX" FT HELIX 107..117 FT /evidence="ECO:0007829|PDB:5UCX" FT HELIX 119..123 FT /evidence="ECO:0007829|PDB:5UCX" FT TURN 124..126 FT /evidence="ECO:0007829|PDB:5UCX" FT STRAND 127..135 FT /evidence="ECO:0007829|PDB:5UCX" FT HELIX 137..144 FT /evidence="ECO:0007829|PDB:5UCX" FT HELIX 148..150 FT /evidence="ECO:0007829|PDB:5UCX" FT STRAND 157..162 FT /evidence="ECO:0007829|PDB:5UCX" FT STRAND 164..166 FT /evidence="ECO:0007829|PDB:5JCG" FT HELIX 167..171 FT /evidence="ECO:0007829|PDB:5UCX" FT TURN 177..180 FT /evidence="ECO:0007829|PDB:5UCX" FT STRAND 184..189 FT /evidence="ECO:0007829|PDB:5UCX" FT STRAND 193..201 FT /evidence="ECO:0007829|PDB:5UCX" FT HELIX 209..225 FT /evidence="ECO:0007829|PDB:5UCX" FT HELIX 244..254 FT /evidence="ECO:0007829|PDB:5UCX" SQ SEQUENCE 256 AA; 27693 MW; 8BEB7F5E55BFE9BE CRC64; MAAAVGRLLR ASVARHVSAI PWGISATAAL RPAACGRTSL TNLLCSGSSQ AKLFSTSSSC HAPAVTQHAP YFKGTAVVNG EFKDLSLDDF KGKYLVLFFY PLDFTFVCPT EIVAFSDKAN EFHDVNCEVV AVSVDSHFSH LAWINTPRKN GGLGHMNIAL LSDLTKQISR DYGVLLEGSG LALRGLFIID PNGVIKHLSV NDLPVGRSVE ETLRLVKAFQ YVETHGEVCP ANWTPDSPTI KPSPAASKEY FQKVNQ //