Full text data of PRDX5
PRDX5
(ACR1)
[Confidence: low (only semi-automatic identification from reviews)]
Peroxiredoxin-5, mitochondrial; 1.11.1.15 (Alu corepressor 1; Antioxidant enzyme B166; AOEB166; Liver tissue 2D-page spot 71B; PLP; Peroxiredoxin V; Prx-V; Peroxisomal antioxidant enzyme; TPx type VI; Thioredoxin peroxidase PMP20; Thioredoxin reductase; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Peroxiredoxin-5, mitochondrial; 1.11.1.15 (Alu corepressor 1; Antioxidant enzyme B166; AOEB166; Liver tissue 2D-page spot 71B; PLP; Peroxiredoxin V; Prx-V; Peroxisomal antioxidant enzyme; TPx type VI; Thioredoxin peroxidase PMP20; Thioredoxin reductase; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P30044
ID PRDX5_HUMAN Reviewed; 214 AA.
AC P30044; A6NC19; A6NG06; B7ZLJ4; B7ZVW3; Q14CK0; Q6IAF2; Q9UBU5;
read moreAC Q9UJU4; Q9UKX4;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 4.
DT 22-JAN-2014, entry version 150.
DE RecName: Full=Peroxiredoxin-5, mitochondrial;
DE EC=1.11.1.15;
DE AltName: Full=Alu corepressor 1;
DE AltName: Full=Antioxidant enzyme B166;
DE Short=AOEB166;
DE AltName: Full=Liver tissue 2D-page spot 71B;
DE AltName: Full=PLP;
DE AltName: Full=Peroxiredoxin V;
DE Short=Prx-V;
DE AltName: Full=Peroxisomal antioxidant enzyme;
DE AltName: Full=TPx type VI;
DE AltName: Full=Thioredoxin peroxidase PMP20;
DE AltName: Full=Thioredoxin reductase;
DE Flags: Precursor;
GN Name=PRDX5; Synonyms=ACR1; ORFNames=SBBI10;
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] (ISOFORM MITOCHONDRIAL), AND VARIANT
RP CYS-33.
RX PubMed=10095767; DOI=10.1046/j.1432-1327.1999.00162.x;
RA Kropotov A., Sedova V., Ivanov V., Sazeeva N., Tomilin A.,
RA Krutilina R., Oei S.L., Griesenbeck J., Buchlow G., Tomilin N.;
RT "A novel human DNA-binding protein with sequence similarity to a
RT subfamily of redox proteins which is able to repress RNA-polymerase-
RT III-driven transcription of the Alu-family retroposons in vitro.";
RL Eur. J. Biochem. 260:336-346(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYTOPLASMIC+PEROXISOMAL), AND
RP CHARACTERIZATION.
RX PubMed=10514471; DOI=10.1074/jbc.274.42.29897;
RA Yamashita H., Avraham S., Jiang S., London R., Van Veldhoven P.P.,
RA Subramani S., Rogers R.A., Avraham H.;
RT "Characterization of human and murine PMP20 peroxisomal proteins that
RT exhibit antioxidant activity in vitro.";
RL J. Biol. Chem. 274:29897-29904(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MITOCHONDRIAL), PROTEIN SEQUENCE
RP OF 54-90, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, CHARACTERIZATION,
RP AND VARIANT CYS-33.
RC TISSUE=Lung;
RX PubMed=10521424; DOI=10.1074/jbc.274.43.30451;
RA Knoops B., Clippe A., Bogard C., Arsalane K., Wattiez R., Hermans C.,
RA Duconseille E., Falmagne P., Bernard A.;
RT "Cloning and characterization of AOEB166, a novel mammalian
RT antioxidant enzyme of the peroxiredoxin family.";
RL J. Biol. Chem. 274:30451-30458(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYTOPLASMIC+PEROXISOMAL), AND
RP VARIANT CYS-33.
RX PubMed=10679306; DOI=10.1006/bbrc.2000.2231;
RA Zhou Y., Kok K.H., Chun A.C.S., Wong C.M., Wu H.W., Lin M.C.M.,
RA Fung P.C.W., Kung H.-F., Jin D.-Y.;
RT "Mouse peroxiredoxin V is a thioredoxin peroxidase that inhibits p53-
RT induced apoptosis.";
RL Biochem. Biophys. Res. Commun. 268:921-927(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS, AND CHARACTERIZATION.
RX PubMed=10751410; DOI=10.1074/jbc.M001943200;
RA Seo M.S., Kang S.W., Kim K., Baines I.C., Lee T.H., Rhee S.G.;
RT "Identification of a new type of mammalian peroxiredoxin that forms an
RT intramolecular disulfide as a reaction intermediate.";
RL J. Biol. Chem. 275:20346-20354(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYTOPLASMIC+PEROXISOMAL).
RA Kim I.H., Jeong W.;
RT "A new type of human thiol peroxidase (Human TPx type VI).";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MITOCHONDRIAL), AND VARIANT
RP CYS-33.
RA Zhang W., Li N., Wan T., Cao X.;
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM
RP CYTOPLASMIC+PEROXISOMAL).
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MITOCHONDRIAL), AND
RP VARIANT CYS-33.
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 (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT CYS-33.
RG NIEHS SNPs program;
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS MITOCHONDRIAL; 3 AND
RP 4), AND VARIANT CYS-33.
RC TISSUE=Brain, and Medulla oblongata;
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 [13]
RP PROTEIN SEQUENCE OF 54-63.
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 [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-83, 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 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 [16]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS).
RX PubMed=11518528; DOI=10.1006/jmbi.2001.4853;
RA Declercq J.-P., Evrard C., Clippe A., Stricht D.V., Bernard A.,
RA Knoops B.;
RT "Crystal structure of human peroxiredoxin 5, a novel type of mammalian
RT peroxiredoxin at 1.5-A resolution.";
RL J. Mol. Biol. 311:751-759(2001).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 54-214, AND DISULFIDE BOND.
RX PubMed=18489898; DOI=10.1016/j.abb.2008.04.036;
RA Smeets A., Marchand C., Linard D., Knoops B., Declercq J.P.;
RT "The crystal structures of oxidized forms of human peroxiredoxin 5
RT with an intramolecular disulfide bond confirm the proposed enzymatic
RT mechanism for atypical 2-Cys peroxiredoxins.";
RL Arch. Biochem. Biophys. 477:98-104(2008).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 54-214 IN COMPLEX WITH
RP DITHIOTHREITOL, AND ACTIVE SITE.
RX PubMed=20643143; DOI=10.1016/j.jmb.2010.07.022;
RA Hall A., Parsonage D., Poole L.B., Karplus P.A.;
RT "Structural evidence that peroxiredoxin catalytic power is based on
RT transition-state stabilization.";
RL J. Mol. Biol. 402:194-209(2010).
RN [19]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-157.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Reduces hydrogen peroxide and alkyl hydroperoxides with
CC reducing equivalents provided through the thioredoxin system.
CC Involved in intracellular redox signaling.
CC -!- CATALYTIC ACTIVITY: 2 R'-SH + ROOH = R'-S-S-R' + H(2)O + ROH.
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Isoform Mitochondrial: Mitochondrion.
CC -!- SUBCELLULAR LOCATION: Isoform Cytoplasmic+peroxisomal: Cytoplasm.
CC Peroxisome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=4;
CC Name=Mitochondrial;
CC IsoId=P30044-1; Sequence=Displayed;
CC Name=Cytoplasmic+peroxisomal;
CC IsoId=P30044-2; Sequence=VSP_018829;
CC Name=3;
CC IsoId=P30044-3; Sequence=VSP_045783;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=P30044-4; Sequence=VSP_046682;
CC Note=Produced by alternative splicing;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- SIMILARITY: Belongs to the peroxiredoxin 2 family.
CC -!- SIMILARITY: Contains 1 thioredoxin domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF17200.1; Type=Frameshift; Positions=14, 30;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/prdx5/";
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DR EMBL; AF231705; AAF78899.1; -; mRNA.
DR EMBL; AF124993; AAF27531.1; -; mRNA.
DR EMBL; AF110731; AAF03750.1; -; mRNA.
DR EMBL; AF197952; AAF04856.1; -; mRNA.
DR EMBL; AJ249483; CAB62210.1; -; mRNA.
DR EMBL; AF242525; AAF99605.1; -; mRNA.
DR EMBL; AF112212; AAF17200.1; ALT_FRAME; mRNA.
DR EMBL; CR457203; CAG33484.1; -; mRNA.
DR EMBL; DQ247769; ABB05181.1; -; Genomic_DNA.
DR EMBL; AP001453; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP003774; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC110983; AAI10984.1; -; mRNA.
DR EMBL; BC113723; AAI13724.1; -; mRNA.
DR EMBL; BC113725; AAI13726.1; -; mRNA.
DR EMBL; BC143849; AAI43850.1; -; mRNA.
DR EMBL; BC171733; AAI71733.1; -; mRNA.
DR RefSeq; NP_036226.1; NM_012094.4.
DR RefSeq; NP_857634.1; NM_181651.2.
DR RefSeq; NP_857635.1; NM_181652.2.
DR UniGene; Hs.502823; -.
DR PDB; 1H4O; X-ray; 1.95 A; A/B/C/D/E/F/G/H=54-214.
DR PDB; 1HD2; X-ray; 1.50 A; A=54-214.
DR PDB; 1OC3; X-ray; 2.00 A; A/B/C=54-214.
DR PDB; 1URM; X-ray; 1.70 A; A=54-214.
DR PDB; 2VL2; X-ray; 1.92 A; A/B/C=54-214.
DR PDB; 2VL3; X-ray; 1.83 A; A/B/C=54-214.
DR PDB; 2VL9; X-ray; 2.70 A; A/B/C/D=54-214.
DR PDB; 3MNG; X-ray; 1.45 A; A=54-214.
DR PDBsum; 1H4O; -.
DR PDBsum; 1HD2; -.
DR PDBsum; 1OC3; -.
DR PDBsum; 1URM; -.
DR PDBsum; 2VL2; -.
DR PDBsum; 2VL3; -.
DR PDBsum; 2VL9; -.
DR PDBsum; 3MNG; -.
DR ProteinModelPortal; P30044; -.
DR SMR; P30044; 54-214.
DR IntAct; P30044; 5.
DR MINT; MINT-5002532; -.
DR STRING; 9606.ENSP00000265462; -.
DR DrugBank; DB00995; Auranofin.
DR PeroxiBase; 4448; HsPrxV.
DR PhosphoSite; P30044; -.
DR DMDM; 20141713; -.
DR OGP; P30044; -.
DR REPRODUCTION-2DPAGE; IPI00759663; -.
DR SWISS-2DPAGE; P30044; -.
DR UCD-2DPAGE; P30044; -.
DR PaxDb; P30044; -.
DR PRIDE; P30044; -.
DR DNASU; 25824; -.
DR Ensembl; ENST00000265462; ENSP00000265462; ENSG00000126432.
DR Ensembl; ENST00000347941; ENSP00000335363; ENSG00000126432.
DR Ensembl; ENST00000352435; ENSP00000335334; ENSG00000126432.
DR GeneID; 25824; -.
DR KEGG; hsa:25824; -.
DR UCSC; uc001nzv.3; human.
DR CTD; 25824; -.
DR GeneCards; GC11P064085; -.
DR HGNC; HGNC:9355; PRDX5.
DR HPA; CAB008661; -.
DR MIM; 606583; gene.
DR neXtProt; NX_P30044; -.
DR PharmGKB; PA33726; -.
DR eggNOG; COG0678; -.
DR HOGENOM; HOG000255884; -.
DR HOVERGEN; HBG053675; -.
DR InParanoid; P30044; -.
DR KO; K11187; -.
DR OMA; MSAWGKQ; -.
DR OrthoDB; EOG77Q4XX; -.
DR PhylomeDB; P30044; -.
DR ChiTaRS; PRDX5; human.
DR EvolutionaryTrace; P30044; -.
DR GeneWiki; PRDX5; -.
DR GenomeRNAi; 25824; -.
DR NextBio; 35462441; -.
DR PRO; PR:P30044; -.
DR ArrayExpress; P30044; -.
DR Bgee; P30044; -.
DR CleanEx; HS_PRDX5; -.
DR Genevestigator; P30044; -.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005782; C:peroxisomal matrix; IDA:UniProtKB.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0016209; F:antioxidant activity; IDA:UniProtKB.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:0004601; F:peroxidase activity; IDA:UniProtKB.
DR GO; GO:0051920; F:peroxiredoxin activity; IEA:UniProtKB-EC.
DR GO; GO:0072541; F:peroxynitrite reductase activity; IDA:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IDA:UniProtKB.
DR GO; GO:0001016; F:RNA polymerase III regulatory region DNA binding; IDA:UniProtKB.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:UniProtKB.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IDA:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB.
DR GO; GO:0070995; P:NADPH oxidation; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0051354; P:negative regulation of oxidoreductase activity; IDA:UniProtKB.
DR GO; GO:0016480; P:negative regulation of transcription from RNA polymerase III promoter; IDA:UniProtKB.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IDA:UniProtKB.
DR GO; GO:2001057; P:reactive nitrogen species metabolic process; IDA:UniProtKB.
DR GO; GO:0060785; P:regulation of apoptosis involved in tissue homeostasis; IDA:UniProtKB.
DR Gene3D; 3.40.30.10; -; 1.
DR InterPro; IPR013740; Redoxin.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR Pfam; PF08534; Redoxin; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative initiation;
KW Alternative splicing; Antioxidant; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Disulfide bond; Mitochondrion;
KW Oxidoreductase; Peroxidase; Peroxisome; Polymorphism;
KW Redox-active center; Reference proteome; Transit peptide.
FT TRANSIT 1 52 Mitochondrion (Potential).
FT CHAIN 53 214 Peroxiredoxin-5, mitochondrial.
FT /FTId=PRO_0000023793.
FT DOMAIN 56 214 Thioredoxin.
FT MOTIF 212 214 Microbody targeting signal (By
FT similarity).
FT ACT_SITE 100 100 Cysteine sulfenic acid (-SOH)
FT intermediate (Probable).
FT MOD_RES 75 75 N6-acetyllysine (By similarity).
FT MOD_RES 83 83 N6-acetyllysine.
FT DISULFID 100 204 Redox-active.
FT VAR_SEQ 1 52 Missing (in isoform
FT Cytoplasmic+peroxisomal).
FT /FTId=VSP_018829.
FT VAR_SEQ 57 145 Missing (in isoform 4).
FT /FTId=VSP_046682.
FT VAR_SEQ 102 145 Missing (in isoform 3).
FT /FTId=VSP_045783.
FT VARIANT 33 33 Y -> C (in dbSNP:rs7938623).
FT /FTId=VAR_025049.
FT VARIANT 157 157 F -> L (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036406.
FT MUTAGEN 100 100 C->S: Complete loss of activity.
FT MUTAGEN 125 125 C->S: No change in activity.
FT MUTAGEN 204 204 C->S: Complete loss of activity.
FT CONFLICT 141 141 H -> T (in Ref. 4; AAF04856).
FT STRAND 66 68
FT HELIX 72 74
FT STRAND 75 77
FT HELIX 78 81
FT TURN 82 84
FT STRAND 85 91
FT HELIX 98 102
FT HELIX 104 110
FT HELIX 112 116
FT TURN 117 119
FT STRAND 122 129
FT HELIX 131 140
FT TURN 144 146
FT STRAND 148 151
FT HELIX 156 161
FT HELIX 167 169
FT HELIX 170 173
FT STRAND 181 186
FT STRAND 189 195
FT HELIX 207 213
SQ SEQUENCE 214 AA; 22086 MW; DA1DEB21120254EE CRC64;
MGLAGVCALR RSAGYILVGG AGGQSAAAAA RRYSEGEWAS GGVRSFSRAA AAMAPIKVGD
AIPAVEVFEG EPGNKVNLAE LFKGKKGVLF GVPGAFTPGC SKTHLPGFVE QAEALKAKGV
QVVACLSVND AFVTGEWGRA HKAEGKVRLL ADPTGAFGKE TDLLLDDSLV SIFGNRRLKR
FSMVVQDGIV KALNVEPDGT GLTCSLAPNI ISQL
//
ID PRDX5_HUMAN Reviewed; 214 AA.
AC P30044; A6NC19; A6NG06; B7ZLJ4; B7ZVW3; Q14CK0; Q6IAF2; Q9UBU5;
read moreAC Q9UJU4; Q9UKX4;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 4.
DT 22-JAN-2014, entry version 150.
DE RecName: Full=Peroxiredoxin-5, mitochondrial;
DE EC=1.11.1.15;
DE AltName: Full=Alu corepressor 1;
DE AltName: Full=Antioxidant enzyme B166;
DE Short=AOEB166;
DE AltName: Full=Liver tissue 2D-page spot 71B;
DE AltName: Full=PLP;
DE AltName: Full=Peroxiredoxin V;
DE Short=Prx-V;
DE AltName: Full=Peroxisomal antioxidant enzyme;
DE AltName: Full=TPx type VI;
DE AltName: Full=Thioredoxin peroxidase PMP20;
DE AltName: Full=Thioredoxin reductase;
DE Flags: Precursor;
GN Name=PRDX5; Synonyms=ACR1; ORFNames=SBBI10;
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] (ISOFORM MITOCHONDRIAL), AND VARIANT
RP CYS-33.
RX PubMed=10095767; DOI=10.1046/j.1432-1327.1999.00162.x;
RA Kropotov A., Sedova V., Ivanov V., Sazeeva N., Tomilin A.,
RA Krutilina R., Oei S.L., Griesenbeck J., Buchlow G., Tomilin N.;
RT "A novel human DNA-binding protein with sequence similarity to a
RT subfamily of redox proteins which is able to repress RNA-polymerase-
RT III-driven transcription of the Alu-family retroposons in vitro.";
RL Eur. J. Biochem. 260:336-346(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYTOPLASMIC+PEROXISOMAL), AND
RP CHARACTERIZATION.
RX PubMed=10514471; DOI=10.1074/jbc.274.42.29897;
RA Yamashita H., Avraham S., Jiang S., London R., Van Veldhoven P.P.,
RA Subramani S., Rogers R.A., Avraham H.;
RT "Characterization of human and murine PMP20 peroxisomal proteins that
RT exhibit antioxidant activity in vitro.";
RL J. Biol. Chem. 274:29897-29904(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MITOCHONDRIAL), PROTEIN SEQUENCE
RP OF 54-90, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, CHARACTERIZATION,
RP AND VARIANT CYS-33.
RC TISSUE=Lung;
RX PubMed=10521424; DOI=10.1074/jbc.274.43.30451;
RA Knoops B., Clippe A., Bogard C., Arsalane K., Wattiez R., Hermans C.,
RA Duconseille E., Falmagne P., Bernard A.;
RT "Cloning and characterization of AOEB166, a novel mammalian
RT antioxidant enzyme of the peroxiredoxin family.";
RL J. Biol. Chem. 274:30451-30458(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYTOPLASMIC+PEROXISOMAL), AND
RP VARIANT CYS-33.
RX PubMed=10679306; DOI=10.1006/bbrc.2000.2231;
RA Zhou Y., Kok K.H., Chun A.C.S., Wong C.M., Wu H.W., Lin M.C.M.,
RA Fung P.C.W., Kung H.-F., Jin D.-Y.;
RT "Mouse peroxiredoxin V is a thioredoxin peroxidase that inhibits p53-
RT induced apoptosis.";
RL Biochem. Biophys. Res. Commun. 268:921-927(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS, AND CHARACTERIZATION.
RX PubMed=10751410; DOI=10.1074/jbc.M001943200;
RA Seo M.S., Kang S.W., Kim K., Baines I.C., Lee T.H., Rhee S.G.;
RT "Identification of a new type of mammalian peroxiredoxin that forms an
RT intramolecular disulfide as a reaction intermediate.";
RL J. Biol. Chem. 275:20346-20354(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYTOPLASMIC+PEROXISOMAL).
RA Kim I.H., Jeong W.;
RT "A new type of human thiol peroxidase (Human TPx type VI).";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MITOCHONDRIAL), AND VARIANT
RP CYS-33.
RA Zhang W., Li N., Wan T., Cao X.;
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM
RP CYTOPLASMIC+PEROXISOMAL).
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MITOCHONDRIAL), AND
RP VARIANT CYS-33.
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 (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT CYS-33.
RG NIEHS SNPs program;
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS MITOCHONDRIAL; 3 AND
RP 4), AND VARIANT CYS-33.
RC TISSUE=Brain, and Medulla oblongata;
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 [13]
RP PROTEIN SEQUENCE OF 54-63.
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 [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-83, 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 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 [16]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS).
RX PubMed=11518528; DOI=10.1006/jmbi.2001.4853;
RA Declercq J.-P., Evrard C., Clippe A., Stricht D.V., Bernard A.,
RA Knoops B.;
RT "Crystal structure of human peroxiredoxin 5, a novel type of mammalian
RT peroxiredoxin at 1.5-A resolution.";
RL J. Mol. Biol. 311:751-759(2001).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 54-214, AND DISULFIDE BOND.
RX PubMed=18489898; DOI=10.1016/j.abb.2008.04.036;
RA Smeets A., Marchand C., Linard D., Knoops B., Declercq J.P.;
RT "The crystal structures of oxidized forms of human peroxiredoxin 5
RT with an intramolecular disulfide bond confirm the proposed enzymatic
RT mechanism for atypical 2-Cys peroxiredoxins.";
RL Arch. Biochem. Biophys. 477:98-104(2008).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 54-214 IN COMPLEX WITH
RP DITHIOTHREITOL, AND ACTIVE SITE.
RX PubMed=20643143; DOI=10.1016/j.jmb.2010.07.022;
RA Hall A., Parsonage D., Poole L.B., Karplus P.A.;
RT "Structural evidence that peroxiredoxin catalytic power is based on
RT transition-state stabilization.";
RL J. Mol. Biol. 402:194-209(2010).
RN [19]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-157.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Reduces hydrogen peroxide and alkyl hydroperoxides with
CC reducing equivalents provided through the thioredoxin system.
CC Involved in intracellular redox signaling.
CC -!- CATALYTIC ACTIVITY: 2 R'-SH + ROOH = R'-S-S-R' + H(2)O + ROH.
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Isoform Mitochondrial: Mitochondrion.
CC -!- SUBCELLULAR LOCATION: Isoform Cytoplasmic+peroxisomal: Cytoplasm.
CC Peroxisome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=4;
CC Name=Mitochondrial;
CC IsoId=P30044-1; Sequence=Displayed;
CC Name=Cytoplasmic+peroxisomal;
CC IsoId=P30044-2; Sequence=VSP_018829;
CC Name=3;
CC IsoId=P30044-3; Sequence=VSP_045783;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=P30044-4; Sequence=VSP_046682;
CC Note=Produced by alternative splicing;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- SIMILARITY: Belongs to the peroxiredoxin 2 family.
CC -!- SIMILARITY: Contains 1 thioredoxin domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF17200.1; Type=Frameshift; Positions=14, 30;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/prdx5/";
CC -----------------------------------------------------------------------
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DR EMBL; AF231705; AAF78899.1; -; mRNA.
DR EMBL; AF124993; AAF27531.1; -; mRNA.
DR EMBL; AF110731; AAF03750.1; -; mRNA.
DR EMBL; AF197952; AAF04856.1; -; mRNA.
DR EMBL; AJ249483; CAB62210.1; -; mRNA.
DR EMBL; AF242525; AAF99605.1; -; mRNA.
DR EMBL; AF112212; AAF17200.1; ALT_FRAME; mRNA.
DR EMBL; CR457203; CAG33484.1; -; mRNA.
DR EMBL; DQ247769; ABB05181.1; -; Genomic_DNA.
DR EMBL; AP001453; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP003774; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC110983; AAI10984.1; -; mRNA.
DR EMBL; BC113723; AAI13724.1; -; mRNA.
DR EMBL; BC113725; AAI13726.1; -; mRNA.
DR EMBL; BC143849; AAI43850.1; -; mRNA.
DR EMBL; BC171733; AAI71733.1; -; mRNA.
DR RefSeq; NP_036226.1; NM_012094.4.
DR RefSeq; NP_857634.1; NM_181651.2.
DR RefSeq; NP_857635.1; NM_181652.2.
DR UniGene; Hs.502823; -.
DR PDB; 1H4O; X-ray; 1.95 A; A/B/C/D/E/F/G/H=54-214.
DR PDB; 1HD2; X-ray; 1.50 A; A=54-214.
DR PDB; 1OC3; X-ray; 2.00 A; A/B/C=54-214.
DR PDB; 1URM; X-ray; 1.70 A; A=54-214.
DR PDB; 2VL2; X-ray; 1.92 A; A/B/C=54-214.
DR PDB; 2VL3; X-ray; 1.83 A; A/B/C=54-214.
DR PDB; 2VL9; X-ray; 2.70 A; A/B/C/D=54-214.
DR PDB; 3MNG; X-ray; 1.45 A; A=54-214.
DR PDBsum; 1H4O; -.
DR PDBsum; 1HD2; -.
DR PDBsum; 1OC3; -.
DR PDBsum; 1URM; -.
DR PDBsum; 2VL2; -.
DR PDBsum; 2VL3; -.
DR PDBsum; 2VL9; -.
DR PDBsum; 3MNG; -.
DR ProteinModelPortal; P30044; -.
DR SMR; P30044; 54-214.
DR IntAct; P30044; 5.
DR MINT; MINT-5002532; -.
DR STRING; 9606.ENSP00000265462; -.
DR DrugBank; DB00995; Auranofin.
DR PeroxiBase; 4448; HsPrxV.
DR PhosphoSite; P30044; -.
DR DMDM; 20141713; -.
DR OGP; P30044; -.
DR REPRODUCTION-2DPAGE; IPI00759663; -.
DR SWISS-2DPAGE; P30044; -.
DR UCD-2DPAGE; P30044; -.
DR PaxDb; P30044; -.
DR PRIDE; P30044; -.
DR DNASU; 25824; -.
DR Ensembl; ENST00000265462; ENSP00000265462; ENSG00000126432.
DR Ensembl; ENST00000347941; ENSP00000335363; ENSG00000126432.
DR Ensembl; ENST00000352435; ENSP00000335334; ENSG00000126432.
DR GeneID; 25824; -.
DR KEGG; hsa:25824; -.
DR UCSC; uc001nzv.3; human.
DR CTD; 25824; -.
DR GeneCards; GC11P064085; -.
DR HGNC; HGNC:9355; PRDX5.
DR HPA; CAB008661; -.
DR MIM; 606583; gene.
DR neXtProt; NX_P30044; -.
DR PharmGKB; PA33726; -.
DR eggNOG; COG0678; -.
DR HOGENOM; HOG000255884; -.
DR HOVERGEN; HBG053675; -.
DR InParanoid; P30044; -.
DR KO; K11187; -.
DR OMA; MSAWGKQ; -.
DR OrthoDB; EOG77Q4XX; -.
DR PhylomeDB; P30044; -.
DR ChiTaRS; PRDX5; human.
DR EvolutionaryTrace; P30044; -.
DR GeneWiki; PRDX5; -.
DR GenomeRNAi; 25824; -.
DR NextBio; 35462441; -.
DR PRO; PR:P30044; -.
DR ArrayExpress; P30044; -.
DR Bgee; P30044; -.
DR CleanEx; HS_PRDX5; -.
DR Genevestigator; P30044; -.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005782; C:peroxisomal matrix; IDA:UniProtKB.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0016209; F:antioxidant activity; IDA:UniProtKB.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:0004601; F:peroxidase activity; IDA:UniProtKB.
DR GO; GO:0051920; F:peroxiredoxin activity; IEA:UniProtKB-EC.
DR GO; GO:0072541; F:peroxynitrite reductase activity; IDA:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IDA:UniProtKB.
DR GO; GO:0001016; F:RNA polymerase III regulatory region DNA binding; IDA:UniProtKB.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:UniProtKB.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IDA:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB.
DR GO; GO:0070995; P:NADPH oxidation; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0051354; P:negative regulation of oxidoreductase activity; IDA:UniProtKB.
DR GO; GO:0016480; P:negative regulation of transcription from RNA polymerase III promoter; IDA:UniProtKB.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IDA:UniProtKB.
DR GO; GO:2001057; P:reactive nitrogen species metabolic process; IDA:UniProtKB.
DR GO; GO:0060785; P:regulation of apoptosis involved in tissue homeostasis; IDA:UniProtKB.
DR Gene3D; 3.40.30.10; -; 1.
DR InterPro; IPR013740; Redoxin.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR Pfam; PF08534; Redoxin; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative initiation;
KW Alternative splicing; Antioxidant; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Disulfide bond; Mitochondrion;
KW Oxidoreductase; Peroxidase; Peroxisome; Polymorphism;
KW Redox-active center; Reference proteome; Transit peptide.
FT TRANSIT 1 52 Mitochondrion (Potential).
FT CHAIN 53 214 Peroxiredoxin-5, mitochondrial.
FT /FTId=PRO_0000023793.
FT DOMAIN 56 214 Thioredoxin.
FT MOTIF 212 214 Microbody targeting signal (By
FT similarity).
FT ACT_SITE 100 100 Cysteine sulfenic acid (-SOH)
FT intermediate (Probable).
FT MOD_RES 75 75 N6-acetyllysine (By similarity).
FT MOD_RES 83 83 N6-acetyllysine.
FT DISULFID 100 204 Redox-active.
FT VAR_SEQ 1 52 Missing (in isoform
FT Cytoplasmic+peroxisomal).
FT /FTId=VSP_018829.
FT VAR_SEQ 57 145 Missing (in isoform 4).
FT /FTId=VSP_046682.
FT VAR_SEQ 102 145 Missing (in isoform 3).
FT /FTId=VSP_045783.
FT VARIANT 33 33 Y -> C (in dbSNP:rs7938623).
FT /FTId=VAR_025049.
FT VARIANT 157 157 F -> L (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036406.
FT MUTAGEN 100 100 C->S: Complete loss of activity.
FT MUTAGEN 125 125 C->S: No change in activity.
FT MUTAGEN 204 204 C->S: Complete loss of activity.
FT CONFLICT 141 141 H -> T (in Ref. 4; AAF04856).
FT STRAND 66 68
FT HELIX 72 74
FT STRAND 75 77
FT HELIX 78 81
FT TURN 82 84
FT STRAND 85 91
FT HELIX 98 102
FT HELIX 104 110
FT HELIX 112 116
FT TURN 117 119
FT STRAND 122 129
FT HELIX 131 140
FT TURN 144 146
FT STRAND 148 151
FT HELIX 156 161
FT HELIX 167 169
FT HELIX 170 173
FT STRAND 181 186
FT STRAND 189 195
FT HELIX 207 213
SQ SEQUENCE 214 AA; 22086 MW; DA1DEB21120254EE CRC64;
MGLAGVCALR RSAGYILVGG AGGQSAAAAA RRYSEGEWAS GGVRSFSRAA AAMAPIKVGD
AIPAVEVFEG EPGNKVNLAE LFKGKKGVLF GVPGAFTPGC SKTHLPGFVE QAEALKAKGV
QVVACLSVND AFVTGEWGRA HKAEGKVRLL ADPTGAFGKE TDLLLDDSLV SIFGNRRLKR
FSMVVQDGIV KALNVEPDGT GLTCSLAPNI ISQL
//
MIM
606583
*RECORD*
*FIELD* NO
606583
*FIELD* TI
*606583 PEROXIREDOXIN 5; PRDX5
;;ANTIOXIDANT ENZYME B166; AOEB166
*FIELD* TX
DESCRIPTION
read more
Incomplete reduction of atmospheric oxygen generates potent oxidizing
agents, including reactive oxygen species (ROS) and their toxic
byproducts. Sources of ROS include mitochondria and peroxisomes.
Protection from ROS is mediated by nonenzymatic agents, such as
vitamins; enzymes, such as catalase (CAT; 115500); and low molecular
weight reducing agents, such as thioredoxin (TXN; 187700). PRDX5 is a
member of the peroxiredoxin family and may play an antioxidant
protective role in various tissues under nonpathologic conditions and
during inflammatory processes.
CLONING
By 2-dimensional electrophoresis of bronchoalveolar lavage (BAL) fluid
and microsequence analysis to create an analytical map of BAL fluid
proteins, Wattiez et al. (1999) identified a 17-kD protein with a pI of
6.9 that they termed B166. Using PCR amplification of lung cDNA with
degenerate primers corresponding to the N terminus of B166, followed by
5-prime and 3-prime RACE, Knoops et al. (1999) isolated a cDNA encoding
PRDX5, which they called antioxidant enzyme B166 (AOEB166). Sequence
analysis predicted that the 214-amino acid protein is 90% identical to
the rat sequence after the second methionine (in human, met53). PRDX5
displays mitochondrial presequence features and has 3 cysteines
implicated in antioxidant activity and a C-terminal SQL peroxisomal
targeting sequence. Northern blot analysis revealed ubiquitous
expression of a 1.0-kb PRDX5 transcript in tissues and cell lines. Dot
blot analysis indicated highest expression in thyroid gland, trachea,
kidney, lung, adrenal gland, heart, and colon. Fluorescence microscopy
demonstrated expression in mitochondria and peroxisomes. Rat Prdx5
expression was increased in lungs after the instillation of
lipopolysaccharide. Functional analysis showed that PRDX5 has
antioxidant activity equivalent to that of CAT. Knoops et al. (1999)
noted that PRDX5 was the first peroxiredoxin to be associated with
peroxisomes, and they suggested that it may play a protective role
against ROS generated in these organelles.
BIOCHEMICAL FEATURES
Declercq et al. (2001) reported the crystal structure of PRDX5 in its
reduced form at 1.5-angstrom resolution. The structure revealed a
thioredoxin-like domain and that PRDX5 does not form a dimer. The
authors noted the presence of a benzoate ion, a hydroxyl radical
scavenger, close to the active-site pocket.
GENE FUNCTION
Wang et al. (2001) used PCR, Western blot, immunohistochemical, and in
situ hybridization analyses to show that PRDX5 expression is increased
in degenerative tendon compared with normal tendon. While PRDX5 was
localized to fibroblasts in normal tendon, it was localized to
fibroblasts and endothelial cells in degenerative tendon.
Wang et al. (2002) mimicked osteoarthritis by exposing cultured human
articular cartilage chondrocytes and cartilage explants to tumor
necrosis factor-alpha (191160) and interleukin-1-beta (147720).
Intracellular peroxide levels began to rise 3 hours after cytokine
challenge. PRDX5 mRNA and protein levels increased at 12 hours, and the
increase in PRDX5 expression correlated with reduced peroxide levels.
Wang et al. (2002) concluded that PRDX5 plays a protective role against
oxidative stress in human cartilage.
Acting as a signal, hydrogen peroxide circumvents antioxidant defense by
overoxidizing peroxiredoxins (Prxs), the enzymes that metabolize
peroxides. Budanov et al. (2004) showed that sestrins, a family of
proteins whose expression is modulated by p53, are required for
regeneration of Prxs containing cys-SO(2)H, thus reestablishing the
antioxidant firewall. Sestrins contain a predicted redox-active domain
homologous to AhpD, the enzyme catalyzing the reduction of a bacterial
peroxiredoxin, AhpC. Purified Hi95 (sestrin-2; 607767) protein supported
adenosine triphosphate-dependent reduction of overoxidized PrxI in
vitro, indicating that unlike AhpD, which is a disulfide reductase,
sestrins are cysteine sulfinyl reductases.
MAPPING
By radiation hybrid analysis, Knoops et al. (1999) mapped the PRDX5 gene
to chromosome 11q13, a region associated with atopic hypersensitivity.
*FIELD* RF
1. Budanov, A. V.; Sablina, A. A.; Feinstein, E.; Koonin, E. V.; Chumakov,
P. M.: Regeneration of peroxiredoxins by p53-regulated sestrins,
homologs of bacterial AhpD. Science 304: 596-600, 2004.
2. Declercq, J.-P.; Evrard, C.; Clippe, A.; Stricht, D. V.; Bernard,
A.; Knoops, B.: Crystal structure of human peroxiredoxin 5, a novel
type of mammalian peroxiredoxin at 1.5-angstrom resolution. J. Mol.
Biol. 311: 751-759, 2001.
3. Knoops, B.; Clippe, A.; Bogard, C.; Arsalane, K.; Wattiez, R.;
Hermans, C.; Duconseille, E.; Falmagne, P.; Bernard, A.: Cloning
and characterization of AOEB166, a novel mammalian antioxidant enzyme
of the peroxiredoxin family. J. Biol. Chem. 274: 30451-30458, 1999.
4. Wang, M.-X.; Wei, A.; Yuan, J.; Clippe, A.; Bernard, A.; Knoops,
B.; Murrell, G. A. C.: Antioxidant enzyme peroxiredoxin 5 is upregulated
in degenerative human tendon. Biochem. Biophys. Res. Commun. 284:
667-673, 2001.
5. Wang, M.-X.; Wei, A.; Yuan, J.; Trickett, A.; Knoops, B.; Murrell,
G. A. C.: Expression and regulation of peroxiredoxin 5 in human osteoarthritis. FEBS
Lett. 531: 359-362, 2002.
6. Wattiez, R.; Hermans, C.; Bernard, A.; Lesur, O.; Falmagne, P.
: Human bronchoalveolar lavage fluid: two-dimensional gel electrophoresis,
amino acid microsequencing and identification of major proteins. Electrophoresis 20:
1634-1645, 1999.
*FIELD* CN
Ada Hamosh - updated: 4/30/2004
Patricia A. Hartz - updated: 2/10/2003
*FIELD* CD
Paul J. Converse: 12/21/2001
*FIELD* ED
alopez: 04/30/2004
terry: 4/30/2004
mgross: 2/11/2003
terry: 2/10/2003
terry: 3/5/2002
mgross: 1/2/2002
mgross: 12/21/2001
*RECORD*
*FIELD* NO
606583
*FIELD* TI
*606583 PEROXIREDOXIN 5; PRDX5
;;ANTIOXIDANT ENZYME B166; AOEB166
*FIELD* TX
DESCRIPTION
read more
Incomplete reduction of atmospheric oxygen generates potent oxidizing
agents, including reactive oxygen species (ROS) and their toxic
byproducts. Sources of ROS include mitochondria and peroxisomes.
Protection from ROS is mediated by nonenzymatic agents, such as
vitamins; enzymes, such as catalase (CAT; 115500); and low molecular
weight reducing agents, such as thioredoxin (TXN; 187700). PRDX5 is a
member of the peroxiredoxin family and may play an antioxidant
protective role in various tissues under nonpathologic conditions and
during inflammatory processes.
CLONING
By 2-dimensional electrophoresis of bronchoalveolar lavage (BAL) fluid
and microsequence analysis to create an analytical map of BAL fluid
proteins, Wattiez et al. (1999) identified a 17-kD protein with a pI of
6.9 that they termed B166. Using PCR amplification of lung cDNA with
degenerate primers corresponding to the N terminus of B166, followed by
5-prime and 3-prime RACE, Knoops et al. (1999) isolated a cDNA encoding
PRDX5, which they called antioxidant enzyme B166 (AOEB166). Sequence
analysis predicted that the 214-amino acid protein is 90% identical to
the rat sequence after the second methionine (in human, met53). PRDX5
displays mitochondrial presequence features and has 3 cysteines
implicated in antioxidant activity and a C-terminal SQL peroxisomal
targeting sequence. Northern blot analysis revealed ubiquitous
expression of a 1.0-kb PRDX5 transcript in tissues and cell lines. Dot
blot analysis indicated highest expression in thyroid gland, trachea,
kidney, lung, adrenal gland, heart, and colon. Fluorescence microscopy
demonstrated expression in mitochondria and peroxisomes. Rat Prdx5
expression was increased in lungs after the instillation of
lipopolysaccharide. Functional analysis showed that PRDX5 has
antioxidant activity equivalent to that of CAT. Knoops et al. (1999)
noted that PRDX5 was the first peroxiredoxin to be associated with
peroxisomes, and they suggested that it may play a protective role
against ROS generated in these organelles.
BIOCHEMICAL FEATURES
Declercq et al. (2001) reported the crystal structure of PRDX5 in its
reduced form at 1.5-angstrom resolution. The structure revealed a
thioredoxin-like domain and that PRDX5 does not form a dimer. The
authors noted the presence of a benzoate ion, a hydroxyl radical
scavenger, close to the active-site pocket.
GENE FUNCTION
Wang et al. (2001) used PCR, Western blot, immunohistochemical, and in
situ hybridization analyses to show that PRDX5 expression is increased
in degenerative tendon compared with normal tendon. While PRDX5 was
localized to fibroblasts in normal tendon, it was localized to
fibroblasts and endothelial cells in degenerative tendon.
Wang et al. (2002) mimicked osteoarthritis by exposing cultured human
articular cartilage chondrocytes and cartilage explants to tumor
necrosis factor-alpha (191160) and interleukin-1-beta (147720).
Intracellular peroxide levels began to rise 3 hours after cytokine
challenge. PRDX5 mRNA and protein levels increased at 12 hours, and the
increase in PRDX5 expression correlated with reduced peroxide levels.
Wang et al. (2002) concluded that PRDX5 plays a protective role against
oxidative stress in human cartilage.
Acting as a signal, hydrogen peroxide circumvents antioxidant defense by
overoxidizing peroxiredoxins (Prxs), the enzymes that metabolize
peroxides. Budanov et al. (2004) showed that sestrins, a family of
proteins whose expression is modulated by p53, are required for
regeneration of Prxs containing cys-SO(2)H, thus reestablishing the
antioxidant firewall. Sestrins contain a predicted redox-active domain
homologous to AhpD, the enzyme catalyzing the reduction of a bacterial
peroxiredoxin, AhpC. Purified Hi95 (sestrin-2; 607767) protein supported
adenosine triphosphate-dependent reduction of overoxidized PrxI in
vitro, indicating that unlike AhpD, which is a disulfide reductase,
sestrins are cysteine sulfinyl reductases.
MAPPING
By radiation hybrid analysis, Knoops et al. (1999) mapped the PRDX5 gene
to chromosome 11q13, a region associated with atopic hypersensitivity.
*FIELD* RF
1. Budanov, A. V.; Sablina, A. A.; Feinstein, E.; Koonin, E. V.; Chumakov,
P. M.: Regeneration of peroxiredoxins by p53-regulated sestrins,
homologs of bacterial AhpD. Science 304: 596-600, 2004.
2. Declercq, J.-P.; Evrard, C.; Clippe, A.; Stricht, D. V.; Bernard,
A.; Knoops, B.: Crystal structure of human peroxiredoxin 5, a novel
type of mammalian peroxiredoxin at 1.5-angstrom resolution. J. Mol.
Biol. 311: 751-759, 2001.
3. Knoops, B.; Clippe, A.; Bogard, C.; Arsalane, K.; Wattiez, R.;
Hermans, C.; Duconseille, E.; Falmagne, P.; Bernard, A.: Cloning
and characterization of AOEB166, a novel mammalian antioxidant enzyme
of the peroxiredoxin family. J. Biol. Chem. 274: 30451-30458, 1999.
4. Wang, M.-X.; Wei, A.; Yuan, J.; Clippe, A.; Bernard, A.; Knoops,
B.; Murrell, G. A. C.: Antioxidant enzyme peroxiredoxin 5 is upregulated
in degenerative human tendon. Biochem. Biophys. Res. Commun. 284:
667-673, 2001.
5. Wang, M.-X.; Wei, A.; Yuan, J.; Trickett, A.; Knoops, B.; Murrell,
G. A. C.: Expression and regulation of peroxiredoxin 5 in human osteoarthritis. FEBS
Lett. 531: 359-362, 2002.
6. Wattiez, R.; Hermans, C.; Bernard, A.; Lesur, O.; Falmagne, P.
: Human bronchoalveolar lavage fluid: two-dimensional gel electrophoresis,
amino acid microsequencing and identification of major proteins. Electrophoresis 20:
1634-1645, 1999.
*FIELD* CN
Ada Hamosh - updated: 4/30/2004
Patricia A. Hartz - updated: 2/10/2003
*FIELD* CD
Paul J. Converse: 12/21/2001
*FIELD* ED
alopez: 04/30/2004
terry: 4/30/2004
mgross: 2/11/2003
terry: 2/10/2003
terry: 3/5/2002
mgross: 1/2/2002
mgross: 12/21/2001