Reviewed, UniProtKB/Swiss-Prot Q06830 (PRDX1_HUMAN)

Names and origin

Protein names

Recommended name:
    Peroxiredoxin-1
    EC=1.11.1.15
Alternative name(s):
    Thioredoxin peroxidase 2
    Thioredoxin-dependent peroxide reductase 2
    Proliferation-associated gene protein
      Short name=PAG
    Natural killer cell-enhancing factor A
      Short name=NKEF-A

Gene names

Name:	PRDX1
Synonyms:	PAGA, PAGB, TDPX2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	199 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (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' + H(2)O + ROH.
Subunit structure	Homodimer; disulfide-linked, upon oxidation By similarity. May form heterodimers with AOP2.
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.
Post-translational modification	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. 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.
Sequence similarities	Belongs to the ahpC/TSA family. Contains 1 thioredoxin domain.
Sequence caution	The sequence CAI13097.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Domain	Redox-active center
Molecular function	Antioxidant Oxidoreductase Peroxidase
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cell proliferation Traceable author statement. Source: ProtInc cell redox homeostasis Inferred from electronic annotation. Source: InterPro hydrogen peroxide catabolic process Ref.10 Inferred from direct assay. Source: MGI oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW skeletal system development Traceable author statement. Source: ProtInc
Cellular component	melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay. Source: MGI
Molecular function	peroxiredoxin activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AR	P10275	2	EBI-353193,EBI-608057

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 199

199

Peroxiredoxin-1

PRO_0000135076

Regions

Domain

6 – 165

160

Thioredoxin

Sites

Active site

52

1

Cysteine sulfenic acid (-SOH) intermediate

Amino acid modifications

Modified residue

90

1

Phosphothreonine; by CDC2

Modified residue

183

1

Phosphothreonine

Modified residue

194

1

Phosphotyrosine

Disulfide bond

52

Interchain (with C-173); in linked form

Disulfide bond

173

Interchain (with C-52); in linked form

Natural variations

Natural variant

62

1

R → G

VAR_025050

Experimental info

Mutagenesis

90

1

T → A: Abolishes phosphorylation by CDC2; 30% reduction in enzymatic activity

Mutagenesis

90

1

T → D: 87% reduction in enzymatic activity

Sequence conflict

147

1

L → P Ref.2

Sequence conflict

149 – 150

2

VG → CC Ref.2

Sequence conflict

189

1

Q → P Ref.2

Sequence conflict

191

1

S → T Ref.2

Secondary structure

1

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199

Helix Strand Turn

Details...

Beta strand

16 – 20

5

Beta strand

26 – 30

5

Helix

31 – 34

4

Beta strand

37 – 43

7

Helix

54 – 61

8

Helix

63 – 67

5

Turn

68 – 70

3

Beta strand

71 – 79

9

Helix

81 – 88

8

Helix

92 – 94

3

Beta strand

104 – 106

3

Helix

111 – 115

5

Turn

121 – 123

3

Beta strand

128 – 133

6

Beta strand

137 – 145

9

Helix

153 – 167

15

Beta strand

169 – 171

3

Beta strand

181 – 184

4

Sequences

	Sequence		Length	Mass (Da)
	Q06830-1 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: 8F68E56D75BF5304	FASTA	199	22,110
	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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A human cDNA corresponding to a gene overexpressed during cell proliferation encodes a product sharing homology with amoebic and bacterial proteins." Prosperi M.T., Ferbus D., Karczinski I., Goubin G. J. Biol. Chem. 268:11050-11056(1993) [PubMed: 8496166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning and sequence analysis of candidate human natural killer-enhancing factor genes." Shau H., Butterfield L.H., Chiu R., Kim A. Immunogenetics 40:129-134(1994) [PubMed: 8026862] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." 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. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	NIEHS SNPs program Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLY-62.
[6]	"The DNA sequence and biological annotation of human chromosome 1." 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. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Urinary bladder.
[8]	Lubec G., Afjehi-Sadat L. Submitted (MAR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 141-151 AND 159-168, MASS SPECTROMETRY. Tissue: Brain and Cajal-Retzius cell.
[9]	"A method for detection of overoxidation of cysteines: peroxiredoxins are oxidized in vivo at the active-site cysteine during oxidative stress." Wagner E., Luche S., Penna L., Chevallet M., van Dorsselaer A., Leize-Wagner E., Rabilloud T. Biochem. J. 366:777-785(2002) [PubMed: 12059788] [Abstract] Cited for: OVEROXIDATION AT CYS-52.
[10]	"Regulation of peroxiredoxin I activity by Cdc2-mediated phosphorylation." Chang T.-S., Jeong W., Choi S.Y., Yu S., Kang S.W., Rhee S.G. J. Biol. Chem. 277:25370-25376(2002) [PubMed: 11986303] [Abstract] Cited for: PHOSPHORYLATION AT THR-90, MUTAGENESIS OF THR-90.
[11]	"Inactivation of human peroxiredoxin I during catalysis as the result of the oxidation of the catalytic site cysteine to cysteine-sulfinic acid." Yang K.S., Kang S.W., Woo H.A., Hwang S.C., Chae H.Z., Kim K., Rhee S.G. J. Biol. Chem. 277:38029-38036(2002) [PubMed: 12161445] [Abstract] Cited for: OVEROXIDATION AT CYS-52.
[12]	"Regeneration of peroxiredoxins during recovery after oxidative stress: only some overoxidized peroxiredoxins can be reduced during recovery after oxidative stress." Chevallet M., Wagner E., Luche S., van Dorsselaer A., Leize-Wagner E., Rabilloud T. J. Biol. Chem. 278:37146-37153(2003) [PubMed: 12853451] [Abstract] Cited for: RETROREDUCTION OF CYS-52, MASS SPECTROMETRY.
[13]	"Reversing the inactivation of peroxiredoxins caused by cysteine sulfinic acid formation." Woo H.A., Chae H.Z., Hwang S.C., Yang K.S., Kang S.W., Kim K., Rhee S.G. Science 300:653-656(2003) [PubMed: 12714748] [Abstract] Cited for: RETROREDUCTION OF CYS-52, MASS SPECTROMETRY.
[14]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." 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. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-194, MASS SPECTROMETRY.
[15]	"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes." 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. J. Proteome Res. 5:3135-3144(2006) [PubMed: 17081065] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[16]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

X67951 mRNA. Translation: CAA48137.1.
L19184 mRNA. Translation: AAA50464.1.
BT019740 mRNA. Translation: AAV38545.1.
CR407652 mRNA. Translation: CAG28580.1.
DQ297142 Genomic DNA. Translation: ABB84465.1.
AL451136 Genomic DNA. Translation: CAI13095.1.
AL451136 Genomic DNA. Translation: CAI13096.1.
AL451136 Genomic DNA. Translation: CAI13097.1. Sequence problems.
BC007063 mRNA. Translation: AAH07063.1.
BC021683 mRNA. Translation: AAH21683.1.

PIR

A46711.

RefSeq

NP_002565.1.
NP_859047.1.
NP_859048.1.

UniGene

Hs.180909

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2RII	X-ray	2.60	A/B	1-199	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q06830.

Protein family/group databases

PeroxiBase

4501. Hs2CysPrx01.

PTM databases

PhosphoSite

Q06830.

2-D gel databases

SWISS-2DPAGE

Q06830.

DOSAC-COBS-2DPAGE

Q06830.

OGP

Q06830.

Genome annotation databases

Ensembl

ENSG00000117450. Homo sapiens. [Contig view]

GeneID

5052.

KEGG

hsa:5052.

Organism-specific databases

H-InvDB

HIX0000533.

HGNC

HGNC:9352. PRDX1.

HPA

CAB004682.
HPA007730.

MIM

176763. gene.

PharmGKB

PA33722.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

Q06830.

HOVERGEN

Q06830.

Gene expression databases

ArrayExpress

Q06830.

CleanEx

HS_PRDX1.

GermOnline

ENSG00000117450. Homo sapiens.

Family and domain databases

InterPro

IPR000866. AhpC-TSA.
IPR012335. Thioredoxin_fold.
[Graphical view]

Gene3D

G3DSA:3.40.30.10. Thioredoxin_fold. 1 hit.

Pfam

PF00578. AhpC-TSA. 1 hit.
[Graphical view]

PROSITE

PS51352. THIOREDOXIN_2. 1 hit.
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