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UniProtKB/Swiss-Prot entry Q06830


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name PRDX1_HUMAN
Primary accession number Q06830
Secondary accession numbers P35703 Q2V576 Q5T154 Q5T155
Integrated into Swiss-Prot on June 1, 1994
Sequence was last modified on June 1, 1994 (Sequence version 1)
Annotations were last modified on    September 2, 2008 (Entry version 96)
Name and origin of the protein
Protein name Peroxiredoxin-1
Synonyms EC 1.11.1.15
Thioredoxin peroxidase 2
Thioredoxin-dependent peroxide reductase 2
Proliferation-associated gene protein
PAG
Natural killer cell-enhancing factor A
NKEF-A
Gene name
Name: PRDX1
Synonyms: PAGA, PAGB, TDPX2
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=8496166 [NCBI, ExPASy, EBI, Israel, Japan]
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).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1007/BF00188176; PubMed=8026862 [NCBI, ExPASy, EBI, Israel, Japan]
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).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.;
"Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).";
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-62.
NIEHS SNPs program;
Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature04727; PubMed=16710414 [NCBI, ExPASy, EBI, Israel, Japan]
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
"The DNA sequence and biological annotation of human chromosome 1.";
Nature 441:315-321(2006).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Urinary bladder;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
PROTEIN SEQUENCE OF 141-151 AND 159-168, AND MASS SPECTROMETRY.
TISSUE=Brain, and Cajal-Retzius cell;
Lubec G., Afjehi-Sadat L.;
Submitted (MAR-2007) to UniProtKB.
[9]
OVEROXIDATION AT CYS-52.
DOI=10.1042/BJ20020525; PubMed=12059788 [NCBI, ExPASy, EBI, Israel, Japan]
Wagner E., Luche S., Penna L., Chevallet M., van Dorsselaer A., Leize-Wagner E., Rabilloud T.;
"A method for detection of overoxidation of cysteines: peroxiredoxins are oxidized in vivo at the active-site cysteine during oxidative stress.";
Biochem. J. 366:777-785(2002).
[10]
PHOSPHORYLATION AT THR-90, AND MUTAGENESIS OF THR-90.
DOI=10.1074/jbc.M110432200; PubMed=11986303 [NCBI, ExPASy, EBI, Israel, Japan]
Chang T.-S., Jeong W., Choi S.Y., Yu S., Kang S.W., Rhee S.G.;
"Regulation of peroxiredoxin I activity by Cdc2-mediated phosphorylation.";
J. Biol. Chem. 277:25370-25376(2002).
[11]
OVEROXIDATION AT CYS-52.
DOI=10.1074/jbc.M206626200; PubMed=12161445 [NCBI, ExPASy, EBI, Israel, Japan]
Yang K.S., Kang S.W., Woo H.A., Hwang S.C., Chae H.Z., Kim K., Rhee S.G.;
"Inactivation of human peroxiredoxin I during catalysis as the result of the oxidation of the catalytic site cysteine to cysteine-sulfinic acid.";
J. Biol. Chem. 277:38029-38036(2002).
[12]
RETROREDUCTION OF CYS-52, AND MASS SPECTROMETRY.
DOI=10.1074/jbc.M305161200; PubMed=12853451 [NCBI, ExPASy, EBI, Israel, Japan]
Chevallet M., Wagner E., Luche S., van Dorsselaer A., Leize-Wagner E., Rabilloud T.;
"Regeneration of peroxiredoxins during recovery after oxidative stress: only some overoxidized peroxiredoxins can be reduced during recovery after oxidative stress.";
J. Biol. Chem. 278:37146-37153(2003).
[13]
RETROREDUCTION OF CYS-52, AND MASS SPECTROMETRY.
DOI=10.1126/science.1080273; PubMed=12714748 [NCBI, ExPASy, EBI, Israel, Japan]
Woo H.A., Chae H.Z., Hwang S.C., Yang K.S., Kang S.W., Kim K., Rhee S.G.;
"Reversing the inactivation of peroxiredoxins caused by cysteine sulfinic acid formation.";
Science 300:653-656(2003).
[14]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-194, AND MASS SPECTROMETRY.
DOI=10.1038/nbt1046; PubMed=15592455 [NCBI, ExPASy, EBI, Israel, Japan]
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.;
"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
Nat. Biotechnol. 23:94-101(2005).
[15]
SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
DOI=10.1021/pr060363j; PubMed=17081065 [NCBI, ExPASy, EBI, Israel, Japan]
Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes.";
J. Proteome Res. 5:3135-3144(2006).
[16]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183, AND MASS SPECTROMETRY.
DOI=10.1073/pnas.0611217104; PubMed=17287340 [NCBI, ExPASy, EBI, Israel, Japan]
Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.;
"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry.";
Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007).
Comments
  • FUNCTION: Involved in redox regulation of the cell. Reduces peroxides with reducing equivalents provided through the thioredoxin system but not from glutaredoxin. May play an important role in eliminating peroxides generated during metabolism. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2).
  • CATALYTIC ACTIVITY: 2 R'-SH + ROOH = R'-S-S-R' + H2O + ROH.
  • SUBUNIT: Homodimer; disulfide-linked, upon oxidation (By similarity). May form heterodimers with AOP2.
  • INTERACTION:
    P10275:AR; NbExp=2; IntAct=EBI-353193, EBI-608057;
  • SUBCELLULAR LOCATION: Cytoplasm. Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
  • INDUCTION: Constitutively expressed in most human cells; is induced to higher levels upon serum stimulation in untransformed and transformed cells.
  • PTM: Phosphorylated on Thr-90 during the M-phase, which leads to a more than 80% decrease in enzymatic activity.
  • MISCELLANEOUS: The active site is the redox-active Cys-52 oxidized to Cys-SOH. Cys-SOH rapidly reacts with Cys-173-SH of the other subunit to form an intermolecular disulfide with a concomitant homodimer formation. The enzyme may be subsequently regenerated by reduction of the disulfide by thioredoxin.
  • MISCELLANEOUS: Inactivated upon oxidative stress by overoxidation of Cys-52 to Cys-SO(2)H and Cys-SO(3)H. Cys-SO(2)H is retroreduced to Cys-SOH after removal of H(2)O(2), while Cys-SO(3)H may be irreversibly oxidized.
  • SIMILARITY: Belongs to the ahpC/TSA family.
  • SIMILARITY: Contains 1 thioredoxin domain.
  • SEQUENCE CAUTION:
    • Sequence=CAI13097.1; Type=Erroneous gene model prediction;
  • WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PAGID266.html";.
  • WEB RESOURCE: Name=NIEHS SNPs; URL="http://egp.gs.washington.edu/data/prdx1/";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
X67951; CAA48137.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L19184; AAA50464.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BT019740; AAV38545.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
CR407652; CAG28580.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
DQ297142; ABB84465.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL451136; CAI13095.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL451136; CAI13096.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL451136; CAI13097.1; ALT_SEQ; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC007063; AAH07063.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC021683; AAH21683.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A46711; A46711.
RefSeq NP_002565.1; -.
NP_859047.1; -.
NP_859048.1; -.
UniGene Hs.180909
3D structure databases
PDB
2RII; X-ray; 2.60 A; A/B=1-199.[ExPASy / RCSB / EBI]
PDBsum 2RII; -.
ModBase Q06830.
Protein-protein interaction databases
IntAct Q06830; -.
Protein family/group databases
PeroxiBase 4501; Hs2CysPrx01.
PTM databases
PhosphoSite Q06830; -.
2D gel databases
SWISS-2DPAGE Q06830; -.
DOSAC-COBS-2DPAGE Q06830; -.
OGP Q06830; -.
Organism-specific databases
H-InvDB HIX0000533; -.
HGNC HGNC:9352; PRDX1.
GenAtlas PRDX1.
HPA CAB004682; -.
HPA007730; -.
MIM 176763; gene. [NCBI / EBI]
PharmGKB PA33722; -.
GeneCards Q06830.
Gene expression databases
ArrayExpress Q06830; -.
CleanEx HS_PRDX1; -.
GermOnline ENSG00000117450; Homo sapiens.
Ontologies
GO
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0008283; Biological process: cell proliferation (traceable author statement from ProtInc).
GO:0001501; Biological process: skeletal development (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR000866; AhpC-TSA.
IPR012335; Thioredoxin_fold.
Graphical view of domain structure.
Gene3D G3DSA:3.40.30.10; Thioredoxin_fold; 1.
Pfam PF00578; AhpC-TSA; 1.
Pfam graphical view of domain structure.
PROSITE PS51352; THIOREDOXIN_2; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS Q06830.
Genome annotation databases
Ensembl ENSG00000117450; Homo sapiens. [Contig view]
GeneID 5052; -.
KEGG hsa:5052; -.
Phylogenomic databases
HOGENOM Q06830; -.
HOVERGEN Q06830; -.
Other
LinkHub Q06830; -.
SOURCE PRDX1; Homo sapiens.
ProtoNet Q06830.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Antioxidant; Cytoplasm; Direct protein sequencing; Oxidoreductase; Peroxidase; Phosphoprotein; Polymorphism; Redox-active center.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   199  199     Peroxiredoxin-1. PRO_0000135076
DOMAIN   6   165  160     Thioredoxin. 
ACT_SITE   52    52        Cysteine sulfenic acid (-SOH) intermediate. 
MOD_RES   90    90        Phosphothreonine; by CDC2. 
MOD_RES   183   183        Phosphothreonine. 
MOD_RES   194   194        Phosphotyrosine. 
DISULFID   52    52        Interchain (with C-173); in linked form. 
DISULFID   173   173        Interchain (with C-52); in linked form. 
VARIANT   62    62  1     R -> G. VAR_025050 [3D]
MUTAGEN   90    90        T->A: Abolishes phosphorylation by CDC2; 30% reduction in enzymatic activity. 
MUTAGEN   90    90        T->D: 87% reduction in enzymatic activity. 
CONFLICT   147   147        L -> P (in Ref. 2). 
CONFLICT   149   150        VG -> CC (in Ref. 2). 
CONFLICT   189   189        Q -> P (in Ref. 2). 
CONFLICT   191   191        S -> T (in Ref. 2). 
Sequence information
Length: 199 AA [This is the length of the unprocessed precursor] Molecular weight: 22110 Da [This is the MW of the unprocessed precursor] CRC64: 8F68E56D75BF5304 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MSSGNAKIGH PAPNFKATAV MPDGQFKDIS LSDYKGKYVV FFFYPLDFTF VCPTEIIAFS 

        70         80         90        100        110        120 
DRAEEFKKLN CQVIGASVDS HFCHLAWVNT PKKQGGLGPM NIPLVSDPKR TIAQDYGVLK 

       130        140        150        160        170        180 
ADEGISFRGL FIIDDKGILR QITVNDLPVG RSVDETLRLV QAFQFTDKHG EVCPAGWKPG 

       190 
SDTIKPDVQK SKEYFSKQK 

Q06830 in FASTA format

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