Reviewed, UniProtKB/Swiss-Prot P30041 (PRDX6_HUMAN)

Names and origin

Protein names

Recommended name:
    Peroxiredoxin-6
    EC=1.11.1.15
Alternative name(s):
    Antioxidant protein 2
    1-Cys peroxiredoxin
      Short name=1-Cys PRX
    Acidic calcium-independent phospholipase A2
      Short name=aiPLA2
    EC=3.1.1.-
    Non-selenium glutathione peroxidase
      Short name=NSGPx
    EC=1.11.1.7
    24 kDa protein
    Liver 2D page spot 40
    Red blood cells page spot 12

Gene names

Name:	PRDX6
Synonyms:	AOP2, KIAA0106

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	224 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved in redox regulation of the cell. Can reduce H2O2 and short chain organic, fatty acid, and phospholipid hydroperoxides. May play a role in the regulation of phospholipid turnover as well as in protection against oxidative injury.
Catalytic activity	2 R'-SH + ROOH = R'-S-S-R' + H2O + ROH. Donor + H2O2 = oxidized donor + 2 H2O.
Subunit structure	Homotetramer. May interact with HTR2A By similarity. Interacts with STH.
Subcellular location	Cytoplasm By similarity. Lysosome By similarity. Cytoplasmic vesicle By similarity. Note: And also found in lung secretory organelles By similarity.
Miscellaneous	The active site is the redox-active Cys-47 oxidized to Cys-SOH. Cys-SOH may rapidly react with a Cys-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. Irreversibly inactivated by overoxidation of Cys-47 (to Cys-SO3H) upon oxidative stress.
Sequence similarities	Belongs to the ahpC/TSA family. Rehydrin subfamily. Contains 1 thioredoxin domain.

Ontologies

Keywords
Biological process	Lipid degradation
Cellular component	Cytoplasm Cytoplasmic vesicle Lysosome
Domain	Redox-active center
Molecular function	Antioxidant Hydrolase Oxidoreductase Peroxidase
PTM	Disulfide bond Phosphoprotein
Technical term	3D-structure Direct protein sequencing Multifunctional enzyme
Gene Ontology (GO)
Biological process	cell redox homeostasis Inferred from electronic annotation. Source: InterPro oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW phospholipid catabolic process Ref.14 Inferred from direct assay. Source: UniProtKB response to oxidative stress Ref.14 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasmic vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Ref.13 Non-traceable author statement. Source: UniProtKB lysosome Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay. Source: HPA
Molecular function	peroxiredoxin activity Inferred from electronic annotation. Source: EC phospholipase A2 activity Ref.14 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8 Ref.9 Ref.10 Ref.11

Chain

2 – 224

223

Peroxiredoxin-6

PRO_0000135102

Regions

Domain

5 – 169

165

Thioredoxin

Sites

Active site

32

1

For phospholipase activity

Active site

47

1

Cysteine sulfenic acid (-SOH) intermediate

Amino acid modifications

Modified residue

44

1

Phosphothreonine Ref.18

Modified residue

89

1

Phosphotyrosine Ref.17

Disulfide bond

47

Interchain; in linked form By similarity

Experimental info

Mutagenesis

32

1

S → A: Loss of AIPLA2 activity, but no effect on NSGPX activity.

Mutagenesis

47

1

C → S: Loss of NSGPX activity, but no effect on AIPLA2 activity.

Secondary structure

1

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224

Helix Strand Turn

Details...

Beta strand

15 – 18

4

Beta strand

21 – 24

4

Helix

25 – 29

5

Beta strand

32 – 40

9

Helix

45 – 62

18

Turn

63 – 65

3

Beta strand

66 – 74

9

Helix

76 – 89

14

Beta strand

102 – 104

3

Helix

109 – 113

5

Beta strand

124 – 126

3

Beta strand

133 – 137

5

Beta strand

141 – 148

8

Helix

157 – 173

17

Beta strand

175 – 177

3

Beta strand

187 – 189

3

Helix

195 – 201

7

Beta strand

219 – 221

3

Sequences

	Sequence		Length	Mass (Da)
	P30041-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 017D955F0FEEDFBC	FASTA	224	25,035
	10 20 30 40 50 60 MPGGLLLGDV APNFEANTTV GRIRFHDFLG DSWGILFSHP RDFTPVCTTE LGRAAKLAPE 70 80 90 100 110 120 FAKRNVKLIA LSIDSVEDHL AWSKDINAYN CEEPTEKLPF PIIDDRNREL AILLGMLDPA 130 140 150 160 170 180 EKDEKGMPVT ARVVFVFGPD KKLKLSILYP ATTGRNFDEI LRVVISLQLT AEKRVATPVD 190 200 210 220 WKDGDSVMVL PTIPEEEAKK LFPKGVFTKE LPSGKKYLRY TPQP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a human cDNA clone for lysosomal type Ca2+-independent phospholipase A2 and properties of the expressed protein." Kim T.-S., Sundaresh C.S., Feinstein S.I., Dodia C., Skach W.R., Jain M.K., Nagase T., Seki N., Ishikawa K., Nomura N., Fisher A.B. J. Biol. Chem. 272:2542-2550(1997) [PubMed: 8999971] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Erratum Kim T.-S., Sundaresh C.S., Feinstein S.I., Dodia C., Skach W.R., Jain M.K., Nagase T., Seki N., Ishikawa K., Nomura N., Fisher A.B. J. Biol. Chem. 272:10981-10981(1997)
[3]	"The human homologue of a bovine non-selenium glutathione peroxidase is a novel keratinocyte growth factor-regulated gene." Frank S., Munz B., Werner S. Oncogene 14:915-921(1997) [PubMed: 9050990] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1." Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S., Tabata S., Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N. DNA Res. 2:37-43(1995) [PubMed: 7788527] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow.
[5]	NIEHS SNPs program Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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: Fetal brain and Testis.
[8]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-22. Tissue: Platelet.
[9]	Lubec G., Vishwanath V., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-22; 25-53; 85-106; 133-142; 145-155; 163-173 AND 175-199, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[10]	"Human liver protein map: a reference database established by microsequencing and gel comparison." Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F., Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R., Appel R.D., Hughes G.J. Electrophoresis 13:992-1001(1992) [PubMed: 1286669] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE OF 2-15. Tissue: Liver.
[11]	"Plasma and red blood cell protein maps: update 1993." Golaz O., Hughes G.J., Frutiger S., Paquet N., Bairoch A., Pasquali C., Sanchez J.-C., Tissot J.-D., Appel R.D., Walzer C., Balant L., Hochstrasser D.F. Electrophoresis 14:1223-1231(1993) [PubMed: 8313871] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE OF 2-13. Tissue: Erythrocyte.
[12]	"DNA probes built and sequenced for microrrays hybridisations." Dominguez O., Lombardia L. Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 14-99.
[13]	"Characterization of a mammalian peroxiredoxin that contains one conserved cysteine." Kang S.W., Baines I.C., Rhee S.G. J. Biol. Chem. 273:6303-6311(1998) [PubMed: 9497358] [Abstract] Cited for: CHARACTERIZATION, MUTAGENESIS.
[14]	"1-Cys peroxiredoxin, a bifunctional enzyme with glutathione peroxidase and phospholipase A2 activities." Chen J.-W., Dodia C., Feinstein S.I., Jain M.K., Fisher A.B. J. Biol. Chem. 275:28421-28427(2000) [PubMed: 10893423] [Abstract] Cited for: CHARACTERIZATION, MUTAGENESIS.
[15]	"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-47.
[16]	"Saitohin, which is nested in the tau locus and confers allele-specific susceptibility to several neurodegenerative diseases, interacts with peroxiredoxin 6." Gao L., Tse S.-W., Conrad C., Andreadis A. J. Biol. Chem. 280:39268-39272(2005) [PubMed: 16186110] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH STH.
[17]	"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-89, MASS SPECTROMETRY.
[18]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-44, MASS SPECTROMETRY.
[19]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[20]	"Crystal structure of a novel human peroxidase enzyme at 2.0-A resolution." Choi H.-J., Kang S.W., Yang C.-H., Rhee S.G., Ryu S.-E. Nat. Struct. Biol. 5:400-406(1998) [PubMed: 9587003] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

NIEHS SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

D14662 mRNA. Translation: BAA03496.1.
DQ230990 Genomic DNA. Translation: ABB02185.1.
AL139142 Genomic DNA. Translation: CAI20936.1.
BC035857 mRNA. Translation: AAH35857.1.
BC053550 mRNA. Translation: AAH53550.1.
AJ844621 mRNA. Translation: CAH59743.1.

IPI

IPI00220301.

RefSeq

NP_004896.1.

UniGene

Hs.120
Hs.573688

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PRX	X-ray	2.00	A/B	1-224	[»]

ModBase

Search...

Protein family/group databases

PeroxiBase

4426. Hs1CysPrx01.

PTM databases

PhosphoSite

P30041.

2-D gel databases

SWISS-2DPAGE

P30041.

Cornea-2DPAGE

P30041.

DOSAC-COBS-2DPAGE

P30041.

OGP

P30041.

REPRODUCTION-2DPAGE

IPI00220301.
P30041.

Siena-2DPAGE

P30041.

Proteomic databases

PeptideAtlas

P30041.

PRIDE

P30041.

Genome annotation databases

Ensembl

ENSG00000117592. Homo sapiens. [Contig view]

GeneID

9588.

KEGG

hsa:9588.

Organism-specific databases

GeneCards

GC01P171713.

H-InvDB

HIX0001339.
HIX0028696.

HGNC

HGNC:16753. PRDX6.

HPA

CAB008663.
HPA006983.

MIM

602316. gene.

PharmGKB

PA134992760.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P30041.

HOVERGEN

P30041.

OMA

P30041. TARVVFI.

Enzyme and pathway databases

BRENDA

1.11.1.15. 247.
1.11.1.7. 247.

Gene expression databases

ArrayExpress

P30041.

Bgee

P30041.

CleanEx

HS_PRDX6.

GermOnline

ENSG00000117592. Homo sapiens.

Family and domain databases

InterPro

IPR000866. Alkyl_hydroperoxide_Rdtase.
IPR019479. Peroxiredoxin_C.
IPR017936. Thioredoxin-like.
IPR012335. Thioredoxin_fold.
[Graphical view]

Gene3D

G3DSA:3.40.30.10. Thioredoxin_fold. 1 hit.

Pfam

PF10417. 1-cysPrx_C. 1 hit.
PF00578. AhpC-TSA. 1 hit.
[Graphical view]

PROSITE

PS51352. THIOREDOXIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

35979.

SOURCE

Search...

Entry information

Entry name

PRDX6_HUMAN

Accession

Primary (citable) accession number: P30041
Secondary accession number(s): P32077, Q5TAH4, Q5ZEZ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 105 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)