ID   PRDX3_HUMAN             Reviewed;         256 AA.
AC   P30048; P35690; Q0D2H1; Q13776; Q5T5V2; Q96HK4;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 3.
DT   04-NOV-2008, entry version 107.
DE   RecName: Full=Thioredoxin-dependent peroxide reductase, mitochondrial;
DE            EC=1.11.1.15;
DE   AltName: Full=Peroxiredoxin-3;
DE   AltName: Full=PRX III;
DE   AltName: Full=Antioxidant protein 1;
DE            Short=AOP-1;
DE   AltName: Full=Protein MER5 homolog;
DE   AltName: Full=HBC189;
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   MEDLINE=95251598; 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].
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   [3]
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   [4]
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   [5]
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   [6]
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   [7]
RP   PROTEIN SEQUENCE OF 63-72.
RC   TISSUE=Liver;
RX   MEDLINE=93162045; 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   [8]
RP   PROTEIN SEQUENCE OF 150-166 AND 171-207, AND MASS SPECTROMETRY.
RC   TISSUE=Brain, and Cajal-Retzius cell;
RA   Lubec G., Vishwanath V.;
RL   Submitted (MAR-2007) to UniProtKB.
RN   [9]
RP   OVEROXIDATION AT CYS-108.
RX   MEDLINE=22201787; 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   [10]
RP   FUNCTION, AND INTERACTION WITH MAP3K13.
RX   MEDLINE=22380812; PubMed=12492477;
RX   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).
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: Homodimer; disulfide-linked, upon oxidation (By
CC       similarity). Binds MAP3K13.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion.
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; 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; 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; -.
DR   RefSeq; NP_054817.2; -.
DR   UniGene; Hs.523302; -.
DR   UniGene; Hs.604267; -.
DR   HSSP; P32119; 1QMV.
DR   SMR; P30048; 63-223.
DR   IntAct; P30048; -.
DR   PeroxiBase; 4492; Hs2CysPrx03.
DR   SWISS-2DPAGE; P30048; -.
DR   OGP; P30048; -.
DR   Siena-2DPAGE; P30048; -.
DR   PeptideAtlas; P30048; -.
DR   Ensembl; ENSG00000165672; Homo sapiens.
DR   GeneID; 10935; -.
DR   KEGG; hsa:10935; -.
DR   NMPDR; fig|9606.3.peg.4727; -.
DR   H-InvDB; HIX0009251; -.
DR   H-InvDB; HIX0035477; -.
DR   H-InvDB; HIX0060125; -.
DR   HGNC; HGNC:9354; PRDX3.
DR   HPA; CAB008656; -.
DR   MIM; 604769; gene.
DR   PharmGKB; PA33724; -.
DR   HOGENOM; P30048; -.
DR   HOVERGEN; P30048; -.
DR   NextBio; 41537; -.
DR   ArrayExpress; P30048; -.
DR   CleanEx; HS_PRDX3; -.
DR   GermOnline; ENSG00000165672; Homo sapiens.
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:caspase inhibitor activity; IMP:UniProtKB.
DR   GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR   GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR   GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:UniProtKB.
DR   GO; GO:0042744; P:hydrogen peroxide catabolic process; IMP:UniProtKB.
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 apoptosis; 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 transcript...; 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   InterPro; IPR000866; AhpC-TSA.
DR   InterPro; IPR012335; Thioredoxin_fold.
DR   Gene3D; G3DSA:3.40.30.10; Thioredoxin_fold; 1.
DR   Pfam; PF00578; AhpC-TSA; 1.
DR   PROSITE; PS51352; THIOREDOXIN_2; 1.
PE   1: Evidence at protein level;
KW   Antioxidant; Direct protein sequencing; Mitochondrion; Oxidoreductase;
KW   Peroxidase; Redox-active center; 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   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.
FT                                /FTId=VAR_025052.
FT   VARIANT     218    218       A -> T.
FT                                /FTId=VAR_025053.
FT   VARIANT     234    234       T -> I.
FT                                /FTId=VAR_025054.
FT   CONFLICT     31     31       R -> W (in Ref. 6; 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
//