Full text data of PRDX3
PRDX3
(AOP1)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Thioredoxin-dependent peroxide reductase, mitochondrial; 1.11.1.15 (Antioxidant protein 1; AOP-1; HBC189; Peroxiredoxin III; Prx-III; Peroxiredoxin-3; Protein MER5 homolog; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Thioredoxin-dependent peroxide reductase, mitochondrial; 1.11.1.15 (Antioxidant protein 1; AOP-1; HBC189; Peroxiredoxin III; Prx-III; Peroxiredoxin-3; Protein MER5 homolog; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P30048
ID PRDX3_HUMAN Reviewed; 256 AA.
AC P30048; B2R7Z0; D3DRC9; P35690; Q0D2H1; Q13776; Q5T5V2; Q96HK4;
read moreDT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 3.
DT 22-JAN-2014, entry version 167.
DE RecName: Full=Thioredoxin-dependent peroxide reductase, mitochondrial;
DE EC=1.11.1.15;
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 Flags: Precursor;
GN Name=PRDX3; Synonyms=AOP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Blood;
RX PubMed=7733872;
RA Tsuji K., Copeland N.G., Jenkins N.A., Obinata M.;
RT "Mammalian antioxidant protein complements alkylhydroperoxide
RT reductase (ahpC) mutation in Escherichia coli.";
RL Biochem. J. 307:377-381(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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].
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].
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
RT 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.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 63-72.
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, AND 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
RT are oxidized in vivo at the active-site cysteine during oxidative
RT 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 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
RT pathway: general properties and factors affecting PrxIII activity and
RT oligomeric state.";
RL J. Mol. Biol. 372:1022-1033(2007).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-91, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [15]
RP INTERACTION WITH NEK6.
RX PubMed=20873783; DOI=10.1021/pr100562w;
RA Vaz Meirelles G., Ferreira Lanza D.C., da Silva J.C.,
RA Santana Bernachi J., Paes Leme A.F., Kobarg J.;
RT "Characterization of hNek6 interactome reveals an important role for
RT its short N-terminal domain and colocalization with proteins at the
RT centrosome.";
RL J. Proteome Res. 9:6298-6316(2010).
RN [16]
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.,
RA Buerckstuemmer T., 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 [17]
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).
CC -!- FUNCTION: Involved in redox regulation of the cell. Protects
CC radical-sensitive enzymes from oxidative damage by a radical-
CC generating system. Acts synergistically with MAP3K13 to regulate
CC the activation of NF-kappa-B in the cytosol.
CC -!- CATALYTIC ACTIVITY: 2 R'-SH + ROOH = R'-S-S-R' + H(2)O + ROH.
CC -!- SUBUNIT: Dodecameric ring assembled from homodimeric units;
CC disulfide-linked, upon oxidation. The rings have an approximate
CC diameter of 150 A and a central hole of 70 A. 3-5% of the rings
CC are interlocked by pairs. Binds MAP3K13. Interacts with NEK6.
CC Interacts with LRRK2.
CC -!- INTERACTION:
CC Q5S007:LRRK2; NbExp=10; IntAct=EBI-748336, EBI-5323863;
CC -!- SUBCELLULAR LOCATION: Mitochondrion.
CC -!- PTM: Phosphorylated by LRRK2; phosphorylation reduces perodixase
CC activity.
CC -!- MISCELLANEOUS: The active site is the redox-active Cys-108
CC oxidized to Cys-SOH. Cys-SOH rapidly reacts with Cys-229-SH of the
CC other subunit to form an intermolecular disulfide with a
CC concomitant homodimer formation. The enzyme may be subsequently
CC regenerated by reduction of the disulfide by thioredoxin.
CC -!- MISCELLANEOUS: Irreversibly inactivated by overoxidation of Cys-
CC 108 (to Cys-SO(3)H) upon oxidative stress.
CC -!- SIMILARITY: Belongs to the AhpC/TSA family.
CC -!- SIMILARITY: Contains 1 thioredoxin domain.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/prdx3/";
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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; CAI15802.1; -; 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 RefSeq; NP_006784.1; NM_006793.3.
DR RefSeq; NP_054817.2; NM_014098.3.
DR UniGene; Hs.523302; -.
DR ProteinModelPortal; P30048; -.
DR SMR; P30048; 63-223.
DR IntAct; P30048; 34.
DR MINT; MINT-195453; -.
DR STRING; 9606.ENSP00000298510; -.
DR PeroxiBase; 4492; Hs2CysPrx03.
DR PhosphoSite; P30048; -.
DR DMDM; 2507171; -.
DR OGP; P30048; -.
DR SWISS-2DPAGE; P30048; -.
DR UCD-2DPAGE; P30048; -.
DR PaxDb; P30048; -.
DR PeptideAtlas; P30048; -.
DR PRIDE; P30048; -.
DR DNASU; 10935; -.
DR Ensembl; ENST00000298510; ENSP00000298510; ENSG00000165672.
DR GeneID; 10935; -.
DR KEGG; hsa:10935; -.
DR UCSC; uc001lec.3; human.
DR CTD; 10935; -.
DR GeneCards; GC10M120917; -.
DR H-InvDB; HIX0035477; -.
DR HGNC; HGNC:9354; PRDX3.
DR HPA; CAB008656; -.
DR MIM; 604769; gene.
DR neXtProt; NX_P30048; -.
DR PharmGKB; PA33724; -.
DR eggNOG; COG0450; -.
DR HOVERGEN; HBG000286; -.
DR InParanoid; P30048; -.
DR KO; K03386; -.
DR OMA; FAHKAWH; -.
DR OrthoDB; EOG7T1RCD; -.
DR PhylomeDB; P30048; -.
DR ChiTaRS; PRDX3; human.
DR GeneWiki; PRDX3; -.
DR GenomeRNAi; 10935; -.
DR NextBio; 41537; -.
DR PRO; PR:P30048; -.
DR ArrayExpress; P30048; -.
DR Bgee; P30048; -.
DR CleanEx; HS_PRDX3; -.
DR Genevestigator; P30048; -.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; 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:0004601; F:peroxidase activity; IEA:UniProtKB-KW.
DR GO; GO:0051920; F:peroxiredoxin activity; IEA:UniProtKB-EC.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IMP:UniProtKB.
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; IMP:UniProtKB.
DR GO; GO:0033673; P:negative regulation of kinase activity; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell 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:0032496; P:response to lipopolysaccharide; ISS:UniProtKB.
DR Gene3D; 3.40.30.10; -; 1.
DR InterPro; IPR000866; AhpC/TSA.
DR InterPro; IPR024706; Peroxiredoxin_AhpC-typ.
DR InterPro; IPR019479; Peroxiredoxin_C.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR Pfam; PF10417; 1-cysPrx_C; 1.
DR Pfam; PF00578; AhpC-TSA; 1.
DR PIRSF; PIRSF000239; AHPC; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Antioxidant; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Mitochondrion;
KW Oxidoreductase; Peroxidase; Phosphoprotein; Polymorphism;
KW Redox-active center; Reference proteome; Transit peptide.
FT TRANSIT 1 62 Mitochondrion.
FT CHAIN 63 256 Thioredoxin-dependent peroxide reductase,
FT mitochondrial.
FT /FTId=PRO_0000023782.
FT DOMAIN 63 221 Thioredoxin.
FT ACT_SITE 108 108 Cysteine sulfenic acid (-SOH)
FT intermediate (By similarity).
FT MOD_RES 91 91 N6-acetyllysine.
FT MOD_RES 146 146 Phosphothreonine (Probable).
FT DISULFID 108 108 Interchain (with C-229); in linked form
FT (By similarity).
FT DISULFID 229 229 Interchain (with C-108); in linked form
FT (By similarity).
FT VARIANT 55 55 S -> R (in dbSNP:rs34698541).
FT /FTId=VAR_025052.
FT VARIANT 170 170 R -> Q (in dbSNP:rs11554902).
FT /FTId=VAR_059546.
FT VARIANT 218 218 A -> T.
FT /FTId=VAR_025053.
FT VARIANT 234 234 T -> I (in dbSNP:rs35697338).
FT /FTId=VAR_025054.
FT MUTAGEN 146 146 T->A: Impairs phosphorylation.
FT CONFLICT 31 31 R -> W (in Ref. 8; AAH08435).
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
//
ID PRDX3_HUMAN Reviewed; 256 AA.
AC P30048; B2R7Z0; D3DRC9; P35690; Q0D2H1; Q13776; Q5T5V2; Q96HK4;
read moreDT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 3.
DT 22-JAN-2014, entry version 167.
DE RecName: Full=Thioredoxin-dependent peroxide reductase, mitochondrial;
DE EC=1.11.1.15;
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 Flags: Precursor;
GN Name=PRDX3; Synonyms=AOP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Blood;
RX PubMed=7733872;
RA Tsuji K., Copeland N.G., Jenkins N.A., Obinata M.;
RT "Mammalian antioxidant protein complements alkylhydroperoxide
RT reductase (ahpC) mutation in Escherichia coli.";
RL Biochem. J. 307:377-381(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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].
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].
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
RT 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.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 63-72.
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, AND 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
RT are oxidized in vivo at the active-site cysteine during oxidative
RT 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 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
RT pathway: general properties and factors affecting PrxIII activity and
RT oligomeric state.";
RL J. Mol. Biol. 372:1022-1033(2007).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-91, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [15]
RP INTERACTION WITH NEK6.
RX PubMed=20873783; DOI=10.1021/pr100562w;
RA Vaz Meirelles G., Ferreira Lanza D.C., da Silva J.C.,
RA Santana Bernachi J., Paes Leme A.F., Kobarg J.;
RT "Characterization of hNek6 interactome reveals an important role for
RT its short N-terminal domain and colocalization with proteins at the
RT centrosome.";
RL J. Proteome Res. 9:6298-6316(2010).
RN [16]
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.,
RA Buerckstuemmer T., 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 [17]
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).
CC -!- FUNCTION: Involved in redox regulation of the cell. Protects
CC radical-sensitive enzymes from oxidative damage by a radical-
CC generating system. Acts synergistically with MAP3K13 to regulate
CC the activation of NF-kappa-B in the cytosol.
CC -!- CATALYTIC ACTIVITY: 2 R'-SH + ROOH = R'-S-S-R' + H(2)O + ROH.
CC -!- SUBUNIT: Dodecameric ring assembled from homodimeric units;
CC disulfide-linked, upon oxidation. The rings have an approximate
CC diameter of 150 A and a central hole of 70 A. 3-5% of the rings
CC are interlocked by pairs. Binds MAP3K13. Interacts with NEK6.
CC Interacts with LRRK2.
CC -!- INTERACTION:
CC Q5S007:LRRK2; NbExp=10; IntAct=EBI-748336, EBI-5323863;
CC -!- SUBCELLULAR LOCATION: Mitochondrion.
CC -!- PTM: Phosphorylated by LRRK2; phosphorylation reduces perodixase
CC activity.
CC -!- MISCELLANEOUS: The active site is the redox-active Cys-108
CC oxidized to Cys-SOH. Cys-SOH rapidly reacts with Cys-229-SH of the
CC other subunit to form an intermolecular disulfide with a
CC concomitant homodimer formation. The enzyme may be subsequently
CC regenerated by reduction of the disulfide by thioredoxin.
CC -!- MISCELLANEOUS: Irreversibly inactivated by overoxidation of Cys-
CC 108 (to Cys-SO(3)H) upon oxidative stress.
CC -!- SIMILARITY: Belongs to the AhpC/TSA family.
CC -!- SIMILARITY: Contains 1 thioredoxin domain.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/prdx3/";
CC -----------------------------------------------------------------------
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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; CAI15802.1; -; 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 RefSeq; NP_006784.1; NM_006793.3.
DR RefSeq; NP_054817.2; NM_014098.3.
DR UniGene; Hs.523302; -.
DR ProteinModelPortal; P30048; -.
DR SMR; P30048; 63-223.
DR IntAct; P30048; 34.
DR MINT; MINT-195453; -.
DR STRING; 9606.ENSP00000298510; -.
DR PeroxiBase; 4492; Hs2CysPrx03.
DR PhosphoSite; P30048; -.
DR DMDM; 2507171; -.
DR OGP; P30048; -.
DR SWISS-2DPAGE; P30048; -.
DR UCD-2DPAGE; P30048; -.
DR PaxDb; P30048; -.
DR PeptideAtlas; P30048; -.
DR PRIDE; P30048; -.
DR DNASU; 10935; -.
DR Ensembl; ENST00000298510; ENSP00000298510; ENSG00000165672.
DR GeneID; 10935; -.
DR KEGG; hsa:10935; -.
DR UCSC; uc001lec.3; human.
DR CTD; 10935; -.
DR GeneCards; GC10M120917; -.
DR H-InvDB; HIX0035477; -.
DR HGNC; HGNC:9354; PRDX3.
DR HPA; CAB008656; -.
DR MIM; 604769; gene.
DR neXtProt; NX_P30048; -.
DR PharmGKB; PA33724; -.
DR eggNOG; COG0450; -.
DR HOVERGEN; HBG000286; -.
DR InParanoid; P30048; -.
DR KO; K03386; -.
DR OMA; FAHKAWH; -.
DR OrthoDB; EOG7T1RCD; -.
DR PhylomeDB; P30048; -.
DR ChiTaRS; PRDX3; human.
DR GeneWiki; PRDX3; -.
DR GenomeRNAi; 10935; -.
DR NextBio; 41537; -.
DR PRO; PR:P30048; -.
DR ArrayExpress; P30048; -.
DR Bgee; P30048; -.
DR CleanEx; HS_PRDX3; -.
DR Genevestigator; P30048; -.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; 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:0004601; F:peroxidase activity; IEA:UniProtKB-KW.
DR GO; GO:0051920; F:peroxiredoxin activity; IEA:UniProtKB-EC.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IMP:UniProtKB.
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; IMP:UniProtKB.
DR GO; GO:0033673; P:negative regulation of kinase activity; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell 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:0032496; P:response to lipopolysaccharide; ISS:UniProtKB.
DR Gene3D; 3.40.30.10; -; 1.
DR InterPro; IPR000866; AhpC/TSA.
DR InterPro; IPR024706; Peroxiredoxin_AhpC-typ.
DR InterPro; IPR019479; Peroxiredoxin_C.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR Pfam; PF10417; 1-cysPrx_C; 1.
DR Pfam; PF00578; AhpC-TSA; 1.
DR PIRSF; PIRSF000239; AHPC; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Antioxidant; Complete proteome;
KW Direct protein sequencing; Disulfide bond; Mitochondrion;
KW Oxidoreductase; Peroxidase; Phosphoprotein; Polymorphism;
KW Redox-active center; Reference proteome; Transit peptide.
FT TRANSIT 1 62 Mitochondrion.
FT CHAIN 63 256 Thioredoxin-dependent peroxide reductase,
FT mitochondrial.
FT /FTId=PRO_0000023782.
FT DOMAIN 63 221 Thioredoxin.
FT ACT_SITE 108 108 Cysteine sulfenic acid (-SOH)
FT intermediate (By similarity).
FT MOD_RES 91 91 N6-acetyllysine.
FT MOD_RES 146 146 Phosphothreonine (Probable).
FT DISULFID 108 108 Interchain (with C-229); in linked form
FT (By similarity).
FT DISULFID 229 229 Interchain (with C-108); in linked form
FT (By similarity).
FT VARIANT 55 55 S -> R (in dbSNP:rs34698541).
FT /FTId=VAR_025052.
FT VARIANT 170 170 R -> Q (in dbSNP:rs11554902).
FT /FTId=VAR_059546.
FT VARIANT 218 218 A -> T.
FT /FTId=VAR_025053.
FT VARIANT 234 234 T -> I (in dbSNP:rs35697338).
FT /FTId=VAR_025054.
FT MUTAGEN 146 146 T->A: Impairs phosphorylation.
FT CONFLICT 31 31 R -> W (in Ref. 8; AAH08435).
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
//
MIM
604769
*RECORD*
*FIELD* NO
604769
*FIELD* TI
*604769 PEROXIREDOXIN 3; PRDX3
;;PRX3;;
ANTIOXIDANT PROTEIN 1; AOP1
*FIELD* TX
DESCRIPTION
read more
Peroxiredoxins inactivate H2O2 by oxidizing a key cysteine residue in
their catalytic center, which is subsequently reduced by thioredoxins
(see 187700). The thioredoxins are subsequently reduced by electrons
from NADPH via thioredoxin reductases (see TXNRD1; 601112). PRDX3 is
localized exclusively in mitochondria (summary by Chiribau et al.,
2008).
CLONING
The mouse Aop1 protein, also called Mer5, may promote early events in
the differentiation of murine erythroleukemia (MEL) cells (Nemoto et
al., 1990). Tsuji et al. (1995) found that mouse Aop1 shares 38% amino
acid sequence identity with the C22 subunit of Salmonella typhimurium
alkylhydroperoxide reductase.
By screening a human leukemia cell line cDNA library with a mouse Aop1
cDNA, Tsuji et al. (1995) isolated a cDNA encoding human AOP1. The
deduced 256-amino acid human AOP1 protein shares 86% amino acid sequence
similarity with mouse Aop1, and significant similarity with both the
human proliferation-associated gene A product (PAGA; 176763) and the
mouse stress-induced peritoneal macrophage protein Msp23. AOP1 also
shows sequence similarity to the S. cerevisiae thiol-specific
antioxidant protein TSA; a surface antigen of Entamoeba histolytica,
which is a pathogenic protozoan that causes diarrhea and organ abscess
formation; and a protein of H. pylori, which is a causative agent in
gastritis, ulcers, and gastric adenocarcinoma.
GENE FUNCTION
Tsuji et al. (1995) demonstrated that recombinant mouse Aop1 could
complement an alkylhydroperoxide reductase mutation in E. coli,
suggesting that Aop1 functions as an antioxidant protein.
Shih et al. (2001) determined that AOP1 interacts with Abrin A-chain
(ABRA), which inhibits protein synthesis and can induce apoptosis. By
immunolocalization studies, they determined that both AOP1 and ABRA
colocalize within the mitochondria. By assays of thiol-dependent
antioxidant activity, they determined that ABRA can attenuate AOP1
activity in a dose-dependent manner. Ectopic expression of AOP1 also
blocked the release of cytochrome c from mitochondria and inhibited
apoptosis in ABRA-treated cells.
Deregulated expression of the MYC transcription factor (190080) is found
in a wide variety of human tumors. The primary transforming activity of
MYC is thought to arise through transcriptional regulation of numerous
target genes. Wonsey et al. (2002) showed that PRDX3, which encodes a
mitochondrial protein of the peroxiredoxin gene family, is such a
target. Expression of PRDX3 is induced by MYC and is reduced in c-myc
-/- cells. Chromatin immunoprecipitation analysis spanning the entire
PRDX3 genomic sequence revealed that MYC binds preferentially to a
930-bp region surrounding exon 1. Wonsey et al. (2002) showed that PRDX3
is required for MYC-mediated proliferation, transformation, and
apoptosis after glucose withdrawal. Results using mitochondria-specific
fluorescent probes demonstrated that PRDX3 is essential for maintaining
mitochondrial mass and membrane potential in transformed rat and human
cells. These data provided evidence that PRDX3 is a MYC target gene that
is required to maintain normal mitochondrial function.
Chiribau et al. (2008) found that the forkhead box transcription factor
FOXO3A (602681) was required for basal expression of PRX3 in human
cardiac fibroblasts. They identified 2 FOXO regulatory sequences in the
promoter region of PRX3 and showed that binding of FOXO3A to both
regulatory sequences was required for FOXO3A-mediated activation of a
PRX3 reporter plasmid. Chiribau et al. (2008) concluded that FOXO3A
mediates PRX3 expression and suggested that this regulation may play a
critical role in the resistance to oxidative stress in cardiac
fibroblasts.
MAPPING
By FISH, Tsuji et al. (1995) mapped the human AOP1 gene, also known as
PRDX3, to 10q25-q26. They mapped the mouse Aop1 gene to the distal
region of chromosome 19.
*FIELD* RF
1. Chiribau, C. B.; Cheng, L.; Cucoranu, I. C.; Yu, Y.-S.; Clempus,
R. E.; Sorescu, D.: FOXO3A regulates peroxiredoxin III expression
in human cardiac fibroblasts. J. Biol. Chem. 283: 8211-8217, 2008.
2. Nemoto, Y.; Yamamoto, T.; Takada, S.; Matsui, Y.; Obinata, M.:
Antisense RNA of the latent period gene (MER5) inhibits the differentiation
of murine erythroleukemia cells. Gene 91: 261-265, 1990.
3. Shih, S.-F.; Wu, Y.-H.; Hung, C.-H.; Yang, H.-Y.; Lin, J.-Y.:
Abrin triggers cell death by inactivating a thiol-specific antioxidant
protein. J. Biol. Chem. 276: 21870-21877, 2001.
4. Tsuji, K.; Copeland, N. G.; Jenkins, N. A.; Obinata, M.: Mammalian
antioxidant protein complements alkylhydroperoxide reductase (ahpC)
mutation in Escherichia coli. Biochem. J. 307: 377-381, 1995.
5. Wonsey, D. R.; Zeller, K. I.; Dang, C. V.: The c-Myc target gene
PRDX3 is required for mitochondrial homeostasis and neoplastic transformation. Proc.
Nat. Acad. Sci. 99: 6649-6654, 2002.
*FIELD* CN
Patricia A. Hartz - updated: 1/29/2010
Victor A. McKusick - updated: 6/14/2002
Patricia A. Hartz - updated: 5/13/2002
*FIELD* CD
Patti M. Sherman: 3/30/2000
*FIELD* ED
mgross: 02/02/2010
mgross: 2/2/2010
terry: 1/29/2010
cwells: 7/1/2002
cwells: 6/27/2002
terry: 6/14/2002
carol: 5/13/2002
alopez: 8/1/2000
mcapotos: 4/12/2000
psherman: 3/30/2000
*RECORD*
*FIELD* NO
604769
*FIELD* TI
*604769 PEROXIREDOXIN 3; PRDX3
;;PRX3;;
ANTIOXIDANT PROTEIN 1; AOP1
*FIELD* TX
DESCRIPTION
read more
Peroxiredoxins inactivate H2O2 by oxidizing a key cysteine residue in
their catalytic center, which is subsequently reduced by thioredoxins
(see 187700). The thioredoxins are subsequently reduced by electrons
from NADPH via thioredoxin reductases (see TXNRD1; 601112). PRDX3 is
localized exclusively in mitochondria (summary by Chiribau et al.,
2008).
CLONING
The mouse Aop1 protein, also called Mer5, may promote early events in
the differentiation of murine erythroleukemia (MEL) cells (Nemoto et
al., 1990). Tsuji et al. (1995) found that mouse Aop1 shares 38% amino
acid sequence identity with the C22 subunit of Salmonella typhimurium
alkylhydroperoxide reductase.
By screening a human leukemia cell line cDNA library with a mouse Aop1
cDNA, Tsuji et al. (1995) isolated a cDNA encoding human AOP1. The
deduced 256-amino acid human AOP1 protein shares 86% amino acid sequence
similarity with mouse Aop1, and significant similarity with both the
human proliferation-associated gene A product (PAGA; 176763) and the
mouse stress-induced peritoneal macrophage protein Msp23. AOP1 also
shows sequence similarity to the S. cerevisiae thiol-specific
antioxidant protein TSA; a surface antigen of Entamoeba histolytica,
which is a pathogenic protozoan that causes diarrhea and organ abscess
formation; and a protein of H. pylori, which is a causative agent in
gastritis, ulcers, and gastric adenocarcinoma.
GENE FUNCTION
Tsuji et al. (1995) demonstrated that recombinant mouse Aop1 could
complement an alkylhydroperoxide reductase mutation in E. coli,
suggesting that Aop1 functions as an antioxidant protein.
Shih et al. (2001) determined that AOP1 interacts with Abrin A-chain
(ABRA), which inhibits protein synthesis and can induce apoptosis. By
immunolocalization studies, they determined that both AOP1 and ABRA
colocalize within the mitochondria. By assays of thiol-dependent
antioxidant activity, they determined that ABRA can attenuate AOP1
activity in a dose-dependent manner. Ectopic expression of AOP1 also
blocked the release of cytochrome c from mitochondria and inhibited
apoptosis in ABRA-treated cells.
Deregulated expression of the MYC transcription factor (190080) is found
in a wide variety of human tumors. The primary transforming activity of
MYC is thought to arise through transcriptional regulation of numerous
target genes. Wonsey et al. (2002) showed that PRDX3, which encodes a
mitochondrial protein of the peroxiredoxin gene family, is such a
target. Expression of PRDX3 is induced by MYC and is reduced in c-myc
-/- cells. Chromatin immunoprecipitation analysis spanning the entire
PRDX3 genomic sequence revealed that MYC binds preferentially to a
930-bp region surrounding exon 1. Wonsey et al. (2002) showed that PRDX3
is required for MYC-mediated proliferation, transformation, and
apoptosis after glucose withdrawal. Results using mitochondria-specific
fluorescent probes demonstrated that PRDX3 is essential for maintaining
mitochondrial mass and membrane potential in transformed rat and human
cells. These data provided evidence that PRDX3 is a MYC target gene that
is required to maintain normal mitochondrial function.
Chiribau et al. (2008) found that the forkhead box transcription factor
FOXO3A (602681) was required for basal expression of PRX3 in human
cardiac fibroblasts. They identified 2 FOXO regulatory sequences in the
promoter region of PRX3 and showed that binding of FOXO3A to both
regulatory sequences was required for FOXO3A-mediated activation of a
PRX3 reporter plasmid. Chiribau et al. (2008) concluded that FOXO3A
mediates PRX3 expression and suggested that this regulation may play a
critical role in the resistance to oxidative stress in cardiac
fibroblasts.
MAPPING
By FISH, Tsuji et al. (1995) mapped the human AOP1 gene, also known as
PRDX3, to 10q25-q26. They mapped the mouse Aop1 gene to the distal
region of chromosome 19.
*FIELD* RF
1. Chiribau, C. B.; Cheng, L.; Cucoranu, I. C.; Yu, Y.-S.; Clempus,
R. E.; Sorescu, D.: FOXO3A regulates peroxiredoxin III expression
in human cardiac fibroblasts. J. Biol. Chem. 283: 8211-8217, 2008.
2. Nemoto, Y.; Yamamoto, T.; Takada, S.; Matsui, Y.; Obinata, M.:
Antisense RNA of the latent period gene (MER5) inhibits the differentiation
of murine erythroleukemia cells. Gene 91: 261-265, 1990.
3. Shih, S.-F.; Wu, Y.-H.; Hung, C.-H.; Yang, H.-Y.; Lin, J.-Y.:
Abrin triggers cell death by inactivating a thiol-specific antioxidant
protein. J. Biol. Chem. 276: 21870-21877, 2001.
4. Tsuji, K.; Copeland, N. G.; Jenkins, N. A.; Obinata, M.: Mammalian
antioxidant protein complements alkylhydroperoxide reductase (ahpC)
mutation in Escherichia coli. Biochem. J. 307: 377-381, 1995.
5. Wonsey, D. R.; Zeller, K. I.; Dang, C. V.: The c-Myc target gene
PRDX3 is required for mitochondrial homeostasis and neoplastic transformation. Proc.
Nat. Acad. Sci. 99: 6649-6654, 2002.
*FIELD* CN
Patricia A. Hartz - updated: 1/29/2010
Victor A. McKusick - updated: 6/14/2002
Patricia A. Hartz - updated: 5/13/2002
*FIELD* CD
Patti M. Sherman: 3/30/2000
*FIELD* ED
mgross: 02/02/2010
mgross: 2/2/2010
terry: 1/29/2010
cwells: 7/1/2002
cwells: 6/27/2002
terry: 6/14/2002
carol: 5/13/2002
alopez: 8/1/2000
mcapotos: 4/12/2000
psherman: 3/30/2000