Full text data of PRDX1
PRDX1
(PAGA, PAGB, TDPX2)
[Confidence: high (present in two of the MS resources)]
Peroxiredoxin-1; 1.11.1.15 (Natural killer cell-enhancing factor A; NKEF-A; Proliferation-associated gene protein; PAG; Thioredoxin peroxidase 2; Thioredoxin-dependent peroxide reductase 2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Peroxiredoxin-1; 1.11.1.15 (Natural killer cell-enhancing factor A; NKEF-A; Proliferation-associated gene protein; PAG; Thioredoxin peroxidase 2; Thioredoxin-dependent peroxide reductase 2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00000874
IPI00000874 Peroxiredoxin 1 Peroxiredoxin 1 membrane n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 1 n/a n/a 1 cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00000874 Peroxiredoxin 1 Peroxiredoxin 1 membrane n/a 1 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 1 n/a n/a 1 cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
Q06830
ID PRDX1_HUMAN Reviewed; 199 AA.
AC Q06830; B5BU26; D3DPZ8; P35703; Q2V576; Q5T154; Q5T155;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-1994, sequence version 1.
DT 22-JAN-2014, entry version 156.
DE RecName: Full=Peroxiredoxin-1;
DE EC=1.11.1.15;
DE AltName: Full=Natural killer cell-enhancing factor A;
DE Short=NKEF-A;
DE AltName: Full=Proliferation-associated gene protein;
DE Short=PAG;
DE AltName: Full=Thioredoxin peroxidase 2;
DE AltName: Full=Thioredoxin-dependent peroxide reductase 2;
GN Name=PRDX1; Synonyms=PAGA, PAGB, TDPX2;
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].
RX PubMed=8496166;
RA Prosperi M.T., Ferbus D., Karczinski I., Goubin G.;
RT "A human cDNA corresponding to a gene overexpressed during cell
RT proliferation encodes a product sharing homology with amoebic and
RT bacterial proteins.";
RL J. Biol. Chem. 268:11050-11056(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8026862; DOI=10.1007/BF00188176;
RA Shau H., Butterfield L.H., Chiu R., Kim A.;
RT "Cloning and sequence analysis of candidate human natural killer-
RT enhancing factor genes.";
RL Immunogenetics 40:129-134(1994).
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 [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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-62.
RG NIEHS SNPs program;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H.,
RA Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M.,
RA Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T.,
RA Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A.,
RA Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K.,
RA Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S.,
RA Isogai T., Imai J., Watanabe S., Nomura N.;
RT "Human protein factory for converting the transcriptome into an in
RT vitro-expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Urinary bladder;
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 [10]
RP PROTEIN SEQUENCE OF 17-35; 93-136; 141-151 AND 159-190, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP OVEROXIDATION AT CYS-52.
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 PHOSPHORYLATION AT THR-90, AND MUTAGENESIS OF THR-90.
RX PubMed=11986303; DOI=10.1074/jbc.M110432200;
RA Chang T.-S., Jeong W., Choi S.Y., Yu S., Kang S.W., Rhee S.G.;
RT "Regulation of peroxiredoxin I activity by Cdc2-mediated
RT phosphorylation.";
RL J. Biol. Chem. 277:25370-25376(2002).
RN [13]
RP OVEROXIDATION AT CYS-52.
RX PubMed=12161445; DOI=10.1074/jbc.M206626200;
RA Yang K.S., Kang S.W., Woo H.A., Hwang S.C., Chae H.Z., Kim K.,
RA Rhee S.G.;
RT "Inactivation of human peroxiredoxin I during catalysis as the result
RT of the oxidation of the catalytic site cysteine to cysteine-sulfinic
RT acid.";
RL J. Biol. Chem. 277:38029-38036(2002).
RN [14]
RP RETROREDUCTION OF CYS-52, AND MASS SPECTROMETRY.
RX PubMed=12853451; DOI=10.1074/jbc.M305161200;
RA Chevallet M., Wagner E., Luche S., van Dorsselaer A., Leize-Wagner E.,
RA Rabilloud T.;
RT "Regeneration of peroxiredoxins during recovery after oxidative
RT stress: only some overoxidized peroxiredoxins can be reduced during
RT recovery after oxidative stress.";
RL J. Biol. Chem. 278:37146-37153(2003).
RN [15]
RP RETROREDUCTION OF CYS-52, AND MASS SPECTROMETRY.
RX PubMed=12714748; DOI=10.1126/science.1080273;
RA Woo H.A., Chae H.Z., Hwang S.C., Yang K.S., Kang S.W., Kim K.,
RA Rhee S.G.;
RT "Reversing the inactivation of peroxiredoxins caused by cysteine
RT sulfinic acid formation.";
RL Science 300:653-656(2003).
RN [16]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2; LYS-7; LYS-16; LYS-27 AND
RP LYS-35, MASS SPECTROMETRY, AND CLEAVAGE OF INITIATOR METHIONINE.
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 [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
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).
CC -!- FUNCTION: Involved in redox regulation of the cell. Reduces
CC peroxides with reducing equivalents provided through the
CC thioredoxin system but not from glutaredoxin. May play an
CC important role in eliminating peroxides generated during
CC metabolism. Might participate in the signaling cascades of growth
CC factors and tumor necrosis factor-alpha by regulating the
CC intracellular concentrations of H(2)O(2). Reduces an
CC intramolecular disulfide bond in GDPD5 that gates the ability to
CC GDPD5 to drive postmitotic motor neuron differentiation (By
CC similarity).
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). May form heterodimers with AOP2. Interacts with
CC GDPD5; forms a mixed-disulfide with GDPD5 (By similarity).
CC -!- INTERACTION:
CC P10275:AR; NbExp=3; IntAct=EBI-353193, EBI-608057;
CC P60484:PTEN; NbExp=7; IntAct=EBI-353193, EBI-696162;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Melanosome. Note=Identified by
CC mass spectrometry in melanosome fractions from stage I to stage
CC IV.
CC -!- INDUCTION: Constitutively expressed in most human cells; is
CC induced to higher levels upon serum stimulation in untransformed
CC and transformed cells.
CC -!- PTM: Phosphorylated on Thr-90 during the M-phase, which leads to a
CC more than 80% decrease in enzymatic activity.
CC -!- MISCELLANEOUS: The active site is the redox-active Cys-52 oxidized
CC to Cys-SOH. Cys-SOH rapidly reacts with Cys-173-SH of the other
CC subunit to form an intermolecular disulfide with a concomitant
CC homodimer formation. The enzyme may be subsequently regenerated by
CC reduction of the disulfide by thioredoxin.
CC -!- MISCELLANEOUS: Inactivated upon oxidative stress by overoxidation
CC of Cys-52 to Cys-SO(2)H and Cys-SO(3)H. Cys-SO(2)H is retroreduced
CC to Cys-SOH after removal of H(2)O(2), while Cys-SO(3)H may be
CC irreversibly oxidized.
CC -!- SIMILARITY: Belongs to the AhpC/TSA family.
CC -!- SIMILARITY: Contains 1 thioredoxin domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAI13097.1; Type=Erroneous gene model prediction;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PAGID266.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/prdx1/";
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DR EMBL; X67951; CAA48137.1; -; mRNA.
DR EMBL; L19184; AAA50464.1; -; mRNA.
DR EMBL; BT019740; AAV38545.1; -; mRNA.
DR EMBL; CR407652; CAG28580.1; -; mRNA.
DR EMBL; DQ297142; ABB84465.1; -; Genomic_DNA.
DR EMBL; AB451262; BAG70076.1; -; mRNA.
DR EMBL; AB451388; BAG70202.1; -; mRNA.
DR EMBL; AL451136; CAI13095.1; -; Genomic_DNA.
DR EMBL; AL451136; CAI13096.1; -; Genomic_DNA.
DR EMBL; AL451136; CAI13097.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471059; EAX06975.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06976.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06978.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06979.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06980.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06981.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06982.1; -; Genomic_DNA.
DR EMBL; BC007063; AAH07063.1; -; mRNA.
DR EMBL; BC021683; AAH21683.1; -; mRNA.
DR PIR; A46711; A46711.
DR RefSeq; NP_001189360.1; NM_001202431.1.
DR RefSeq; NP_002565.1; NM_002574.3.
DR RefSeq; NP_859047.1; NM_181696.2.
DR RefSeq; NP_859048.1; NM_181697.2.
DR RefSeq; XP_005270964.1; XM_005270907.1.
DR UniGene; Hs.180909; -.
DR UniGene; Hs.731900; -.
DR PDB; 2RII; X-ray; 2.60 A; A/B=1-199.
DR PDB; 3HY2; X-ray; 2.10 A; A/B=1-199.
DR PDBsum; 2RII; -.
DR PDBsum; 3HY2; -.
DR ProteinModelPortal; Q06830; -.
DR SMR; Q06830; 3-187.
DR DIP; DIP-33152N; -.
DR IntAct; Q06830; 39.
DR MINT; MINT-4999060; -.
DR STRING; 9606.ENSP00000262746; -.
DR ChEMBL; CHEMBL5315; -.
DR PeroxiBase; 4501; Hs2CysPrx01.
DR PhosphoSite; Q06830; -.
DR DMDM; 548453; -.
DR DOSAC-COBS-2DPAGE; Q06830; -.
DR OGP; Q06830; -.
DR SWISS-2DPAGE; Q06830; -.
DR UCD-2DPAGE; Q06830; -.
DR PaxDb; Q06830; -.
DR PRIDE; Q06830; -.
DR DNASU; 5052; -.
DR Ensembl; ENST00000262746; ENSP00000262746; ENSG00000117450.
DR Ensembl; ENST00000319248; ENSP00000361152; ENSG00000117450.
DR GeneID; 5052; -.
DR KEGG; hsa:5052; -.
DR UCSC; uc001coa.3; human.
DR CTD; 5052; -.
DR GeneCards; GC01M045976; -.
DR HGNC; HGNC:9352; PRDX1.
DR HPA; CAB004682; -.
DR HPA; HPA007730; -.
DR MIM; 176763; gene.
DR neXtProt; NX_Q06830; -.
DR PharmGKB; PA33722; -.
DR eggNOG; COG0450; -.
DR HOVERGEN; HBG000286; -.
DR InParanoid; Q06830; -.
DR KO; K13279; -.
DR OMA; EFKKINC; -.
DR OrthoDB; EOG7T1RCD; -.
DR PhylomeDB; Q06830; -.
DR ChiTaRS; PRDX1; human.
DR EvolutionaryTrace; Q06830; -.
DR GeneWiki; Peroxiredoxin_1; -.
DR GenomeRNAi; 5052; -.
DR NextBio; 19468; -.
DR PRO; PR:Q06830; -.
DR Bgee; Q06830; -.
DR CleanEx; HS_PRDX1; -.
DR Genevestigator; Q06830; -.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005719; C:nuclear euchromatin; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005782; C:peroxisomal matrix; IEA:Ensembl.
DR GO; GO:0020037; F:heme binding; IEA:Ensembl.
DR GO; GO:0008379; F:thioredoxin peroxidase activity; IDA:BHF-UCL.
DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
DR GO; GO:0034101; P:erythrocyte homeostasis; IEA:Ensembl.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IDA:BHF-UCL.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IEA:Ensembl.
DR GO; GO:0042345; P:regulation of NF-kappaB import into nucleus; IEA:Ensembl.
DR GO; GO:0032872; P:regulation of stress-activated MAPK cascade; IEA:Ensembl.
DR GO; GO:0019430; P:removal of superoxide radicals; IEA:Ensembl.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
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 3D-structure; Acetylation; Antioxidant; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Disulfide bond; Oxidoreductase; Peroxidase;
KW Phosphoprotein; Polymorphism; Redox-active center; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 199 Peroxiredoxin-1.
FT /FTId=PRO_0000135076.
FT DOMAIN 6 165 Thioredoxin.
FT ACT_SITE 52 52 Cysteine sulfenic acid (-SOH)
FT intermediate.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 7 7 N6-acetyllysine.
FT MOD_RES 16 16 N6-acetyllysine.
FT MOD_RES 27 27 N6-acetyllysine.
FT MOD_RES 35 35 N6-acetyllysine.
FT MOD_RES 90 90 Phosphothreonine; by CDK1.
FT DISULFID 52 52 Interchain (with C-173); in linked form.
FT DISULFID 173 173 Interchain (with C-52); in linked form.
FT VARIANT 62 62 R -> G (in dbSNP:rs34034070).
FT /FTId=VAR_025050.
FT MUTAGEN 90 90 T->A: Abolishes phosphorylation by CDK1;
FT 30% reduction in enzymatic activity.
FT MUTAGEN 90 90 T->D: 87% reduction in enzymatic
FT activity.
FT CONFLICT 147 147 L -> P (in Ref. 2).
FT CONFLICT 149 150 VG -> CC (in Ref. 2).
FT CONFLICT 189 189 Q -> P (in Ref. 2).
FT CONFLICT 191 191 S -> T (in Ref. 2).
FT STRAND 16 20
FT STRAND 26 30
FT HELIX 31 34
FT STRAND 37 43
FT HELIX 54 61
FT HELIX 63 68
FT STRAND 71 79
FT HELIX 81 88
FT HELIX 92 94
FT STRAND 104 106
FT HELIX 111 115
FT TURN 121 123
FT STRAND 124 126
FT STRAND 128 133
FT STRAND 137 145
FT HELIX 153 168
FT STRAND 169 171
FT HELIX 181 183
SQ SEQUENCE 199 AA; 22110 MW; 8F68E56D75BF5304 CRC64;
MSSGNAKIGH PAPNFKATAV MPDGQFKDIS LSDYKGKYVV FFFYPLDFTF VCPTEIIAFS
DRAEEFKKLN CQVIGASVDS HFCHLAWVNT PKKQGGLGPM NIPLVSDPKR TIAQDYGVLK
ADEGISFRGL FIIDDKGILR QITVNDLPVG RSVDETLRLV QAFQFTDKHG EVCPAGWKPG
SDTIKPDVQK SKEYFSKQK
//
ID PRDX1_HUMAN Reviewed; 199 AA.
AC Q06830; B5BU26; D3DPZ8; P35703; Q2V576; Q5T154; Q5T155;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-1994, sequence version 1.
DT 22-JAN-2014, entry version 156.
DE RecName: Full=Peroxiredoxin-1;
DE EC=1.11.1.15;
DE AltName: Full=Natural killer cell-enhancing factor A;
DE Short=NKEF-A;
DE AltName: Full=Proliferation-associated gene protein;
DE Short=PAG;
DE AltName: Full=Thioredoxin peroxidase 2;
DE AltName: Full=Thioredoxin-dependent peroxide reductase 2;
GN Name=PRDX1; Synonyms=PAGA, PAGB, TDPX2;
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].
RX PubMed=8496166;
RA Prosperi M.T., Ferbus D., Karczinski I., Goubin G.;
RT "A human cDNA corresponding to a gene overexpressed during cell
RT proliferation encodes a product sharing homology with amoebic and
RT bacterial proteins.";
RL J. Biol. Chem. 268:11050-11056(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8026862; DOI=10.1007/BF00188176;
RA Shau H., Butterfield L.H., Chiu R., Kim A.;
RT "Cloning and sequence analysis of candidate human natural killer-
RT enhancing factor genes.";
RL Immunogenetics 40:129-134(1994).
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 [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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-62.
RG NIEHS SNPs program;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H.,
RA Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M.,
RA Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T.,
RA Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A.,
RA Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K.,
RA Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S.,
RA Isogai T., Imai J., Watanabe S., Nomura N.;
RT "Human protein factory for converting the transcriptome into an in
RT vitro-expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Urinary bladder;
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 [10]
RP PROTEIN SEQUENCE OF 17-35; 93-136; 141-151 AND 159-190, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP OVEROXIDATION AT CYS-52.
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 PHOSPHORYLATION AT THR-90, AND MUTAGENESIS OF THR-90.
RX PubMed=11986303; DOI=10.1074/jbc.M110432200;
RA Chang T.-S., Jeong W., Choi S.Y., Yu S., Kang S.W., Rhee S.G.;
RT "Regulation of peroxiredoxin I activity by Cdc2-mediated
RT phosphorylation.";
RL J. Biol. Chem. 277:25370-25376(2002).
RN [13]
RP OVEROXIDATION AT CYS-52.
RX PubMed=12161445; DOI=10.1074/jbc.M206626200;
RA Yang K.S., Kang S.W., Woo H.A., Hwang S.C., Chae H.Z., Kim K.,
RA Rhee S.G.;
RT "Inactivation of human peroxiredoxin I during catalysis as the result
RT of the oxidation of the catalytic site cysteine to cysteine-sulfinic
RT acid.";
RL J. Biol. Chem. 277:38029-38036(2002).
RN [14]
RP RETROREDUCTION OF CYS-52, AND MASS SPECTROMETRY.
RX PubMed=12853451; DOI=10.1074/jbc.M305161200;
RA Chevallet M., Wagner E., Luche S., van Dorsselaer A., Leize-Wagner E.,
RA Rabilloud T.;
RT "Regeneration of peroxiredoxins during recovery after oxidative
RT stress: only some overoxidized peroxiredoxins can be reduced during
RT recovery after oxidative stress.";
RL J. Biol. Chem. 278:37146-37153(2003).
RN [15]
RP RETROREDUCTION OF CYS-52, AND MASS SPECTROMETRY.
RX PubMed=12714748; DOI=10.1126/science.1080273;
RA Woo H.A., Chae H.Z., Hwang S.C., Yang K.S., Kang S.W., Kim K.,
RA Rhee S.G.;
RT "Reversing the inactivation of peroxiredoxins caused by cysteine
RT sulfinic acid formation.";
RL Science 300:653-656(2003).
RN [16]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2; LYS-7; LYS-16; LYS-27 AND
RP LYS-35, MASS SPECTROMETRY, AND CLEAVAGE OF INITIATOR METHIONINE.
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 [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
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).
CC -!- FUNCTION: Involved in redox regulation of the cell. Reduces
CC peroxides with reducing equivalents provided through the
CC thioredoxin system but not from glutaredoxin. May play an
CC important role in eliminating peroxides generated during
CC metabolism. Might participate in the signaling cascades of growth
CC factors and tumor necrosis factor-alpha by regulating the
CC intracellular concentrations of H(2)O(2). Reduces an
CC intramolecular disulfide bond in GDPD5 that gates the ability to
CC GDPD5 to drive postmitotic motor neuron differentiation (By
CC similarity).
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). May form heterodimers with AOP2. Interacts with
CC GDPD5; forms a mixed-disulfide with GDPD5 (By similarity).
CC -!- INTERACTION:
CC P10275:AR; NbExp=3; IntAct=EBI-353193, EBI-608057;
CC P60484:PTEN; NbExp=7; IntAct=EBI-353193, EBI-696162;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Melanosome. Note=Identified by
CC mass spectrometry in melanosome fractions from stage I to stage
CC IV.
CC -!- INDUCTION: Constitutively expressed in most human cells; is
CC induced to higher levels upon serum stimulation in untransformed
CC and transformed cells.
CC -!- PTM: Phosphorylated on Thr-90 during the M-phase, which leads to a
CC more than 80% decrease in enzymatic activity.
CC -!- MISCELLANEOUS: The active site is the redox-active Cys-52 oxidized
CC to Cys-SOH. Cys-SOH rapidly reacts with Cys-173-SH of the other
CC subunit to form an intermolecular disulfide with a concomitant
CC homodimer formation. The enzyme may be subsequently regenerated by
CC reduction of the disulfide by thioredoxin.
CC -!- MISCELLANEOUS: Inactivated upon oxidative stress by overoxidation
CC of Cys-52 to Cys-SO(2)H and Cys-SO(3)H. Cys-SO(2)H is retroreduced
CC to Cys-SOH after removal of H(2)O(2), while Cys-SO(3)H may be
CC irreversibly oxidized.
CC -!- SIMILARITY: Belongs to the AhpC/TSA family.
CC -!- SIMILARITY: Contains 1 thioredoxin domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAI13097.1; Type=Erroneous gene model prediction;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PAGID266.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/prdx1/";
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DR EMBL; X67951; CAA48137.1; -; mRNA.
DR EMBL; L19184; AAA50464.1; -; mRNA.
DR EMBL; BT019740; AAV38545.1; -; mRNA.
DR EMBL; CR407652; CAG28580.1; -; mRNA.
DR EMBL; DQ297142; ABB84465.1; -; Genomic_DNA.
DR EMBL; AB451262; BAG70076.1; -; mRNA.
DR EMBL; AB451388; BAG70202.1; -; mRNA.
DR EMBL; AL451136; CAI13095.1; -; Genomic_DNA.
DR EMBL; AL451136; CAI13096.1; -; Genomic_DNA.
DR EMBL; AL451136; CAI13097.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471059; EAX06975.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06976.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06978.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06979.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06980.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06981.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06982.1; -; Genomic_DNA.
DR EMBL; BC007063; AAH07063.1; -; mRNA.
DR EMBL; BC021683; AAH21683.1; -; mRNA.
DR PIR; A46711; A46711.
DR RefSeq; NP_001189360.1; NM_001202431.1.
DR RefSeq; NP_002565.1; NM_002574.3.
DR RefSeq; NP_859047.1; NM_181696.2.
DR RefSeq; NP_859048.1; NM_181697.2.
DR RefSeq; XP_005270964.1; XM_005270907.1.
DR UniGene; Hs.180909; -.
DR UniGene; Hs.731900; -.
DR PDB; 2RII; X-ray; 2.60 A; A/B=1-199.
DR PDB; 3HY2; X-ray; 2.10 A; A/B=1-199.
DR PDBsum; 2RII; -.
DR PDBsum; 3HY2; -.
DR ProteinModelPortal; Q06830; -.
DR SMR; Q06830; 3-187.
DR DIP; DIP-33152N; -.
DR IntAct; Q06830; 39.
DR MINT; MINT-4999060; -.
DR STRING; 9606.ENSP00000262746; -.
DR ChEMBL; CHEMBL5315; -.
DR PeroxiBase; 4501; Hs2CysPrx01.
DR PhosphoSite; Q06830; -.
DR DMDM; 548453; -.
DR DOSAC-COBS-2DPAGE; Q06830; -.
DR OGP; Q06830; -.
DR SWISS-2DPAGE; Q06830; -.
DR UCD-2DPAGE; Q06830; -.
DR PaxDb; Q06830; -.
DR PRIDE; Q06830; -.
DR DNASU; 5052; -.
DR Ensembl; ENST00000262746; ENSP00000262746; ENSG00000117450.
DR Ensembl; ENST00000319248; ENSP00000361152; ENSG00000117450.
DR GeneID; 5052; -.
DR KEGG; hsa:5052; -.
DR UCSC; uc001coa.3; human.
DR CTD; 5052; -.
DR GeneCards; GC01M045976; -.
DR HGNC; HGNC:9352; PRDX1.
DR HPA; CAB004682; -.
DR HPA; HPA007730; -.
DR MIM; 176763; gene.
DR neXtProt; NX_Q06830; -.
DR PharmGKB; PA33722; -.
DR eggNOG; COG0450; -.
DR HOVERGEN; HBG000286; -.
DR InParanoid; Q06830; -.
DR KO; K13279; -.
DR OMA; EFKKINC; -.
DR OrthoDB; EOG7T1RCD; -.
DR PhylomeDB; Q06830; -.
DR ChiTaRS; PRDX1; human.
DR EvolutionaryTrace; Q06830; -.
DR GeneWiki; Peroxiredoxin_1; -.
DR GenomeRNAi; 5052; -.
DR NextBio; 19468; -.
DR PRO; PR:Q06830; -.
DR Bgee; Q06830; -.
DR CleanEx; HS_PRDX1; -.
DR Genevestigator; Q06830; -.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005719; C:nuclear euchromatin; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005782; C:peroxisomal matrix; IEA:Ensembl.
DR GO; GO:0020037; F:heme binding; IEA:Ensembl.
DR GO; GO:0008379; F:thioredoxin peroxidase activity; IDA:BHF-UCL.
DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
DR GO; GO:0034101; P:erythrocyte homeostasis; IEA:Ensembl.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IDA:BHF-UCL.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IEA:Ensembl.
DR GO; GO:0042345; P:regulation of NF-kappaB import into nucleus; IEA:Ensembl.
DR GO; GO:0032872; P:regulation of stress-activated MAPK cascade; IEA:Ensembl.
DR GO; GO:0019430; P:removal of superoxide radicals; IEA:Ensembl.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
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 3D-structure; Acetylation; Antioxidant; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Disulfide bond; Oxidoreductase; Peroxidase;
KW Phosphoprotein; Polymorphism; Redox-active center; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 199 Peroxiredoxin-1.
FT /FTId=PRO_0000135076.
FT DOMAIN 6 165 Thioredoxin.
FT ACT_SITE 52 52 Cysteine sulfenic acid (-SOH)
FT intermediate.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 7 7 N6-acetyllysine.
FT MOD_RES 16 16 N6-acetyllysine.
FT MOD_RES 27 27 N6-acetyllysine.
FT MOD_RES 35 35 N6-acetyllysine.
FT MOD_RES 90 90 Phosphothreonine; by CDK1.
FT DISULFID 52 52 Interchain (with C-173); in linked form.
FT DISULFID 173 173 Interchain (with C-52); in linked form.
FT VARIANT 62 62 R -> G (in dbSNP:rs34034070).
FT /FTId=VAR_025050.
FT MUTAGEN 90 90 T->A: Abolishes phosphorylation by CDK1;
FT 30% reduction in enzymatic activity.
FT MUTAGEN 90 90 T->D: 87% reduction in enzymatic
FT activity.
FT CONFLICT 147 147 L -> P (in Ref. 2).
FT CONFLICT 149 150 VG -> CC (in Ref. 2).
FT CONFLICT 189 189 Q -> P (in Ref. 2).
FT CONFLICT 191 191 S -> T (in Ref. 2).
FT STRAND 16 20
FT STRAND 26 30
FT HELIX 31 34
FT STRAND 37 43
FT HELIX 54 61
FT HELIX 63 68
FT STRAND 71 79
FT HELIX 81 88
FT HELIX 92 94
FT STRAND 104 106
FT HELIX 111 115
FT TURN 121 123
FT STRAND 124 126
FT STRAND 128 133
FT STRAND 137 145
FT HELIX 153 168
FT STRAND 169 171
FT HELIX 181 183
SQ SEQUENCE 199 AA; 22110 MW; 8F68E56D75BF5304 CRC64;
MSSGNAKIGH PAPNFKATAV MPDGQFKDIS LSDYKGKYVV FFFYPLDFTF VCPTEIIAFS
DRAEEFKKLN CQVIGASVDS HFCHLAWVNT PKKQGGLGPM NIPLVSDPKR TIAQDYGVLK
ADEGISFRGL FIIDDKGILR QITVNDLPVG RSVDETLRLV QAFQFTDKHG EVCPAGWKPG
SDTIKPDVQK SKEYFSKQK
//
MIM
176763
*RECORD*
*FIELD* NO
176763
*FIELD* TI
*176763 PEROXIREDOXIN 1; PRDX1
;;PRXI;;
PROLIFERATION-ASSOCIATED GENE A; PAGA;;
NATURAL KILLER-ENHANCING FACTOR A; NKEFA
read more*FIELD* TX
DESCRIPTION
PRDX1 is a thiol reductase that plays critical roles in oxidative and
thermal stress defense mechanisms through its abilities to metabolize
H2O2 and act as a molecular chaperone, respectively. PRDX1 also reduces
intramolecular cystine bridges (summary by Yan et al., 2009).
CLONING
A cDNA of the PAGA gene was isolated by differential cloning between the
untransformed and the RAS transformed human mammary epithelial cell line
HBL100 (Prosperi et al., 1993). The PAGA gene is constitutively
expressed in most human tissues, but its expression is higher in organs
having a higher level of proliferation. The PAGA cDNA hybridizes to a
single mRNA species of 1.2 kb, encoding a 22-kD protein devoid of known
consensus motifs.
Shau et al. (1994) identified a red blood cell factor, NKEF, that
enhances natural killer (NK) cell activity. By immunoscreening an
erythroleukemia cDNA library, they isolated cDNAs encoding NKEFA and
NKEFB (PRDX2; 600538). The NKEFA and NKEFB proteins contain 199 and 198
amino acids, respectively, and are 75% identical. The authors noted that
proteins related to NKEFA and NKEFB appear to be induced by oxidative
stress. Shau et al. (1994) concluded that in addition to
immunoregulation of NK activity, the NKEFs may be important for cells in
coping with oxidative insults.
GENE FUNCTION
Yan et al. (2009) found that Prdx1 was expressed in differentiating
motor neuron cells in developing embryonic chicken and mouse spinal
cords. Ablation of Prdx1 caused deficits in motor neuron differentiation
similar to those in Gde2 (GDPD5; 609632)-knockout motor neuron
progenitor cells. Immunoprecipitation analysis showed that GDE2
interacted directly with PRDX1 in embryonic chicken spinal cord extracts
and in transfected HEK293T cells. In differentiating spinal cord, Prdx1
was required to activate Gde2 by reducing an intramolecular cystine
bridge between the Gde2 N- and C-terminal domains. Reduction of Gde2
involved formation of a mixed-disulfide Prdx1-Gde2 intermediate and did
not involve the chaperone function of Prdx1. Gde2 mutants that failed to
form the intramolecular cystine showed potent Prdx1-independent
induction of motor neuron differentiation. Yan et al. (2009) concluded
that an intramolecular disulfide bond between the GDE2 N- and C-terminal
domains inhibits GDE2 function, and that reduction of this cystine by
PRDX1 activates GDE2 for the induction of motor neuron differentiation.
GENE STRUCTURE
By physical mapping of the gene from a human genomic cosmid library,
Prosperi et al. (1994) determined that the PAGA gene spans 13 kb and
contains 6 exons. The promoter region is GC-rich and contains a TFIID
motif located 25 nucleotides upstream of the potential site for
initiation of transcription, as well as potential recognition sites for
a variety of trans-acting factors.
BIOCHEMICAL FEATURES
- Crystal Structure
Jonsson et al. (2008) presented the 2.6-angstrom crystal structure of
the human sulfiredoxin (SRX)-PRXI complex. This complex reveals the
complete unfolding of the carboxy terminus of PRX, and its unexpected
packing onto the backside of SRX away from the SRX active site. Binding
studies and activity analyses of site-directed mutants at this interface
showed that the interaction is required for repair to occur. Moreover,
rearrangements in the PRX active site lead to a juxtaposition of the PRX
gly-gly-leu-gly and SRX ATP-binding motifs, providing a structural basis
for the first step of the catalytic mechanism. Jonsson et al. (2008)
concluded that the observed interactions may represent a common mode for
other proteins to bind to PRXs.
MAPPING
Using fluorescence in situ hybridization, Prosperi et al. (1994) mapped
the PAGA gene, also known as PRDX1, to 1p34.1. They also isolated and
sequenced a pseudogene (PAGB) and mapped it to 9p22.
ANIMAL MODEL
Neumann et al. (2003) generated mice with targeted disruption of Prdx1.
Mice lacking Prdx1 were viable and fertile but had a shortened life span
owing to the development beginning at about 9 months of age of severe
hemolytic anemia and several malignant cancers, both of which were
observed at increased frequency in heterozygotes. The hemolytic anemia
was characterized by an increase in erythrocyte reactive oxygen species,
leading to protein oxidation, hemoglobin instability, Heinz body
formation, and decreased erythrocyte life span. The malignancies
included lymphomas, sarcomas, and carcinomas, and were frequently
associated with loss of Prdx1 expression in heterozygotes, which
suggested that this protein functions as a tumor suppressor. Neumann et
al. (2003) also observed that Prdx1-deficient fibroblasts showed
decreased proliferation and increased sensitivity to oxidative DNA
damage, whereas Prdx1-null mice had abnormalities in numbers, phenotype,
and function of natural killer cells. Neumann et al. (2003) concluded
that their results implicate PRDX1 as an important defense against
oxidants in aging mice.
*FIELD* RF
1. Jonsson, T. J.; Johnson, L. C.; Lowther, W. T.: Structure of the
sulphiredoxin-peroxiredoxin complex reveals an essential repair embrace. Nature 451:
98-101, 2008.
2. Neumann, C. A.; Krause, D. S.; Carman, C. V.; Das, S.; Dubey, D.
P.; Abraham, J. L.; Bronson, R. T.; Fujiwara, Y.; Orkin, S. H.; Van
Etten, R. A.: Essential role for the peroxiredoxin Prdx1 in erythrocyte
antioxidant defence and tumour suppression. Nature 424: 561-565,
2003.
3. Prosperi, M.-T.; Apiou, F.; Dutrillaux, B.; Goubin, G.: Organization
and chromosomal assignment of two human PAG gene loci: PAGA encoding
a functional gene and PAGB a processed pseudogene. Genomics 19:
236-241, 1994.
4. Prosperi, M.-T.; Ferbus, D.; Karczinski, I.; Goubin, G.: A human
cDNA corresponding to a gene overexpressed during cell proliferation
encodes a product sharing homology with amoebic and bacterial proteins. J.
Biol. Chem. 268: 11050-11056, 1993.
5. Shau, H.; Butterfield, L. H.; Chiu, R.; Kim, A.: Cloning and sequence
analysis of candidate human natural killer-enhancing factor genes. Immunogenetics 40:
129-134, 1994.
6. Yan, Y.; Sabharwal, P.; Rao, M.; Sockanathan, S.: The antioxidant
enzyme Prdx1 controls neuronal differentiation by thiol-redox-dependent
activation of GDE2. Cell 138: 1209-1221, 2009.
*FIELD* CN
Patricia A. Hartz - updated: 1/28/2010
Ada Hamosh - updated: 3/7/2008
Ada Hamosh - updated: 7/31/2003
Paul J. Converse - updated: 8/13/2001
*FIELD* CD
Victor A. McKusick: 2/9/1994
*FIELD* ED
mgross: 01/29/2010
mgross: 1/29/2010
terry: 1/28/2010
alopez: 3/21/2008
terry: 3/7/2008
alopez: 8/4/2003
terry: 7/31/2003
mgross: 8/13/2001
alopez: 8/1/2000
carol: 2/9/1994
*RECORD*
*FIELD* NO
176763
*FIELD* TI
*176763 PEROXIREDOXIN 1; PRDX1
;;PRXI;;
PROLIFERATION-ASSOCIATED GENE A; PAGA;;
NATURAL KILLER-ENHANCING FACTOR A; NKEFA
read more*FIELD* TX
DESCRIPTION
PRDX1 is a thiol reductase that plays critical roles in oxidative and
thermal stress defense mechanisms through its abilities to metabolize
H2O2 and act as a molecular chaperone, respectively. PRDX1 also reduces
intramolecular cystine bridges (summary by Yan et al., 2009).
CLONING
A cDNA of the PAGA gene was isolated by differential cloning between the
untransformed and the RAS transformed human mammary epithelial cell line
HBL100 (Prosperi et al., 1993). The PAGA gene is constitutively
expressed in most human tissues, but its expression is higher in organs
having a higher level of proliferation. The PAGA cDNA hybridizes to a
single mRNA species of 1.2 kb, encoding a 22-kD protein devoid of known
consensus motifs.
Shau et al. (1994) identified a red blood cell factor, NKEF, that
enhances natural killer (NK) cell activity. By immunoscreening an
erythroleukemia cDNA library, they isolated cDNAs encoding NKEFA and
NKEFB (PRDX2; 600538). The NKEFA and NKEFB proteins contain 199 and 198
amino acids, respectively, and are 75% identical. The authors noted that
proteins related to NKEFA and NKEFB appear to be induced by oxidative
stress. Shau et al. (1994) concluded that in addition to
immunoregulation of NK activity, the NKEFs may be important for cells in
coping with oxidative insults.
GENE FUNCTION
Yan et al. (2009) found that Prdx1 was expressed in differentiating
motor neuron cells in developing embryonic chicken and mouse spinal
cords. Ablation of Prdx1 caused deficits in motor neuron differentiation
similar to those in Gde2 (GDPD5; 609632)-knockout motor neuron
progenitor cells. Immunoprecipitation analysis showed that GDE2
interacted directly with PRDX1 in embryonic chicken spinal cord extracts
and in transfected HEK293T cells. In differentiating spinal cord, Prdx1
was required to activate Gde2 by reducing an intramolecular cystine
bridge between the Gde2 N- and C-terminal domains. Reduction of Gde2
involved formation of a mixed-disulfide Prdx1-Gde2 intermediate and did
not involve the chaperone function of Prdx1. Gde2 mutants that failed to
form the intramolecular cystine showed potent Prdx1-independent
induction of motor neuron differentiation. Yan et al. (2009) concluded
that an intramolecular disulfide bond between the GDE2 N- and C-terminal
domains inhibits GDE2 function, and that reduction of this cystine by
PRDX1 activates GDE2 for the induction of motor neuron differentiation.
GENE STRUCTURE
By physical mapping of the gene from a human genomic cosmid library,
Prosperi et al. (1994) determined that the PAGA gene spans 13 kb and
contains 6 exons. The promoter region is GC-rich and contains a TFIID
motif located 25 nucleotides upstream of the potential site for
initiation of transcription, as well as potential recognition sites for
a variety of trans-acting factors.
BIOCHEMICAL FEATURES
- Crystal Structure
Jonsson et al. (2008) presented the 2.6-angstrom crystal structure of
the human sulfiredoxin (SRX)-PRXI complex. This complex reveals the
complete unfolding of the carboxy terminus of PRX, and its unexpected
packing onto the backside of SRX away from the SRX active site. Binding
studies and activity analyses of site-directed mutants at this interface
showed that the interaction is required for repair to occur. Moreover,
rearrangements in the PRX active site lead to a juxtaposition of the PRX
gly-gly-leu-gly and SRX ATP-binding motifs, providing a structural basis
for the first step of the catalytic mechanism. Jonsson et al. (2008)
concluded that the observed interactions may represent a common mode for
other proteins to bind to PRXs.
MAPPING
Using fluorescence in situ hybridization, Prosperi et al. (1994) mapped
the PAGA gene, also known as PRDX1, to 1p34.1. They also isolated and
sequenced a pseudogene (PAGB) and mapped it to 9p22.
ANIMAL MODEL
Neumann et al. (2003) generated mice with targeted disruption of Prdx1.
Mice lacking Prdx1 were viable and fertile but had a shortened life span
owing to the development beginning at about 9 months of age of severe
hemolytic anemia and several malignant cancers, both of which were
observed at increased frequency in heterozygotes. The hemolytic anemia
was characterized by an increase in erythrocyte reactive oxygen species,
leading to protein oxidation, hemoglobin instability, Heinz body
formation, and decreased erythrocyte life span. The malignancies
included lymphomas, sarcomas, and carcinomas, and were frequently
associated with loss of Prdx1 expression in heterozygotes, which
suggested that this protein functions as a tumor suppressor. Neumann et
al. (2003) also observed that Prdx1-deficient fibroblasts showed
decreased proliferation and increased sensitivity to oxidative DNA
damage, whereas Prdx1-null mice had abnormalities in numbers, phenotype,
and function of natural killer cells. Neumann et al. (2003) concluded
that their results implicate PRDX1 as an important defense against
oxidants in aging mice.
*FIELD* RF
1. Jonsson, T. J.; Johnson, L. C.; Lowther, W. T.: Structure of the
sulphiredoxin-peroxiredoxin complex reveals an essential repair embrace. Nature 451:
98-101, 2008.
2. Neumann, C. A.; Krause, D. S.; Carman, C. V.; Das, S.; Dubey, D.
P.; Abraham, J. L.; Bronson, R. T.; Fujiwara, Y.; Orkin, S. H.; Van
Etten, R. A.: Essential role for the peroxiredoxin Prdx1 in erythrocyte
antioxidant defence and tumour suppression. Nature 424: 561-565,
2003.
3. Prosperi, M.-T.; Apiou, F.; Dutrillaux, B.; Goubin, G.: Organization
and chromosomal assignment of two human PAG gene loci: PAGA encoding
a functional gene and PAGB a processed pseudogene. Genomics 19:
236-241, 1994.
4. Prosperi, M.-T.; Ferbus, D.; Karczinski, I.; Goubin, G.: A human
cDNA corresponding to a gene overexpressed during cell proliferation
encodes a product sharing homology with amoebic and bacterial proteins. J.
Biol. Chem. 268: 11050-11056, 1993.
5. Shau, H.; Butterfield, L. H.; Chiu, R.; Kim, A.: Cloning and sequence
analysis of candidate human natural killer-enhancing factor genes. Immunogenetics 40:
129-134, 1994.
6. Yan, Y.; Sabharwal, P.; Rao, M.; Sockanathan, S.: The antioxidant
enzyme Prdx1 controls neuronal differentiation by thiol-redox-dependent
activation of GDE2. Cell 138: 1209-1221, 2009.
*FIELD* CN
Patricia A. Hartz - updated: 1/28/2010
Ada Hamosh - updated: 3/7/2008
Ada Hamosh - updated: 7/31/2003
Paul J. Converse - updated: 8/13/2001
*FIELD* CD
Victor A. McKusick: 2/9/1994
*FIELD* ED
mgross: 01/29/2010
mgross: 1/29/2010
terry: 1/28/2010
alopez: 3/21/2008
terry: 3/7/2008
alopez: 8/4/2003
terry: 7/31/2003
mgross: 8/13/2001
alopez: 8/1/2000
carol: 2/9/1994