Reviewed, UniProtKB/Swiss-Prot P30048 (PRDX3_HUMAN)

Names and origin

Protein names

Recommended name:
    Thioredoxin-dependent peroxide reductase, mitochondrial
    EC=1.11.1.15
Alternative name(s):
    Peroxiredoxin-3
    PRX III
    Antioxidant protein 1
      Short name=AOP-1
    Protein MER5 homolog
    HBC189

Gene names

Name:	PRDX3
Synonyms:	AOP1

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	256 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. Protects radical-sensitive enzymes from oxidative damage by a radical-generating system. Acts synergistically with MAP3K13 to regulate the activation of NF-kappa-B in the cytosol. Ref.11
Catalytic activity	2 R'-SH + ROOH = R'-S-S-R' + H2O + ROH.
Subunit structure	Homodimer; disulfide-linked, upon oxidation By similarity. Binds MAP3K13.
Subcellular location	Mitochondrion.
Miscellaneous	The active site is the redox-active Cys-108 oxidized to Cys-SOH. Cys-SOH rapidly reacts with Cys-229-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-108 (to Cys-SO3H) upon oxidative stress.
Sequence similarities	Belongs to the ahpC/TSA family. Contains 1 thioredoxin domain.

Ontologies

Keywords
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Redox-active center Transit peptide
Molecular function	Antioxidant Oxidoreductase Peroxidase
PTM	Disulfide bond
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	cell redox homeostasis Inferred from electronic annotation. Source: InterPro cellular response to reactive oxygen species Inferred from mutant phenotype. Source: UniProtKB hydrogen peroxide catabolic process Ref.1 Inferred from mutant phenotype. Source: UniProtKB mitochondrion organization Inferred from mutant phenotype. Source: UniProtKB myeloid cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of apoptosis Inferred from mutant phenotype. Source: UniProtKB negative regulation of kinase activity Inferred from direct assay. Source: UniProtKB oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of NF-kappaB transcription factor activity Ref.11 Inferred from direct assay. Source: UniProtKB positive regulation of cell proliferation Inferred from direct assay. Source: UniProtKB regulation of mitochondrial membrane potential Inferred from mutant phenotype. Source: UniProtKB response to lipopolysaccharide Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	early endosome Inferred from direct assay. Source: UniProtKB mitochondrion Inferred from direct assay. Source: UniProtKB
Molecular function	alkyl hydroperoxide reductase activity Ref.1 Non-traceable author statement. Source: UniProtKB caspase inhibitor activity Inferred from mutant phenotype. Source: UniProtKB peroxiredoxin activity Inferred from electronic annotation. Source: EC protein C-terminus binding Inferred from physical interaction. Source: UniProtKB protein kinase binding Ref.11 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 62	62	Mitochondrion Ref.8
	Chain	63 – 256	194	Thioredoxin-dependent peroxide reductase, mitochondrial		PRO_0000023782
Regions
	Domain	63 – 221	159	Thioredoxin
Sites
	Active site	108	1	Cysteine sulfenic acid (-SOH) intermediate By similarity
Amino acid modifications
	Disulfide bond	108		Interchain (with C-229); in linked form By similarity
	Disulfide bond	229		Interchain (with C-108); in linked form By similarity
Natural variations
	Natural variant	55	1	S → R Ref.5		VAR_025052
	Natural variant	218	1	A → T Ref.5		VAR_025053
	Natural variant	234	1	T → I: dbSNP rs35697338. Ref.5		VAR_025054
Experimental info
	Sequence conflict	31	1	R → W in AAH08435. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	P30048-1 [UniParc]. Last modified November 1, 1997. Version 3. Checksum: 8BEB7F5E55BFE9BE	FASTA	256	27,693
	10 20 30 40 50 60 MAAAVGRLLR ASVARHVSAI PWGISATAAL RPAACGRTSL TNLLCSGSSQ AKLFSTSSSC 70 80 90 100 110 120 HAPAVTQHAP YFKGTAVVNG EFKDLSLDDF KGKYLVLFFY PLDFTFVCPT EIVAFSDKAN 130 140 150 160 170 180 EFHDVNCEVV AVSVDSHFSH LAWINTPRKN GGLGHMNIAL LSDLTKQISR DYGVLLEGSG 190 200 210 220 230 240 LALRGLFIID PNGVIKHLSV NDLPVGRSVE ETLRLVKAFQ YVETHGEVCP ANWTPDSPTI 250 KPSPAASKEY FQKVNQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mammalian antioxidant protein complements alkylhydroperoxide reductase (ahpC) mutation in Escherichia coli." Tsuji K., Copeland N.G., Jenkins N.A., Obinata M. Biochem. J. 307:377-381(1995) [PubMed: 7733872] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Blood.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[3]	"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].
[4]	"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].
[5]	NIEHS SNPs program Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-55; THR-218 AND ILE-234.
[6]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [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: Bone marrow, Skeletal muscle, Testis, Urinary bladder and Uterus.
[8]	"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: PROTEIN SEQUENCE OF 63-72. Tissue: Liver.
[9]	Lubec G., Vishwanath V., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 74-93; 149-166 AND 171-214, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[10]	"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-108.
[11]	"Mixed lineage kinase LZK and antioxidant protein-1 activate NF-kappaB synergistically." Masaki M., Ikeda A., Shiraki E., Oka S., Kawasaki T. Eur. J. Biochem. 270:76-83(2003) [PubMed: 12492477] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAP3K13.
[12]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	D49396 mRNA. Translation: BAA08389.1. AK313169 mRNA. Translation: BAG35987.1. CR450344 mRNA. Translation: CAG29340.1. BT020007 mRNA. Translation: AAV38810.1. DQ298752 Genomic DNA. Translation: ABB84468.1. AL355861 Genomic DNA. Translation: CAI15802.1. BC002685 mRNA. Translation: AAH02685.1. BC007062 mRNA. Translation: AAH07062.1. BC008435 mRNA. Translation: AAH08435.1. BC009601 mRNA. Translation: AAH09601.1. BC021691 mRNA. Translation: AAH21691.1. BC022373 mRNA. Translation: AAH22373.1. BC059169 mRNA. Translation: AAH59169.1. BC111397 mRNA. Translation: AAI11398.1.
IPI	IPI00024919.
RefSeq	NP_006784.1. NP_054817.2.
UniGene	Hs.523302 Hs.604267
3D structure databases
HSSP	HSSP built from PDB template 1QMV based on UniProtKB P32119.
SMR	P30048. Positions 63-223.
ModBase	Search...
Protein-protein interaction databases
IntAct	P30048. 3 interactions.
Protein family/group databases
PeroxiBase	4492. Hs2CysPrx03.
PTM databases
PhosphoSite	P30048.
2-D gel databases
SWISS-2DPAGE	P30048.
OGP	P30048.
Siena-2DPAGE	P30048.
Proteomic databases
PeptideAtlas	P30048.
PRIDE	P30048.
Genome annotation databases
Ensembl	ENSG00000165672. Homo sapiens. [Contig view]
GeneID	10935.
KEGG	hsa:10935.
NMPDR	fig|9606.3.peg.4727.
Organism-specific databases
GeneCards	GC10M120917.
H-InvDB	HIX0009251. HIX0035477. HIX0060125.
HGNC	HGNC:9354. PRDX3.
HPA	CAB008656.
MIM	604769. gene.
PharmGKB	PA33724.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P30048.
HOVERGEN	P30048.
OMA	P30048. ANPDEVC.
Enzyme and pathway databases
BRENDA	1.11.1.15. 247.
Gene expression databases
ArrayExpress	P30048.
Bgee	P30048.
CleanEx	HS_PRDX3.
GermOnline	ENSG00000165672. 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	41537.
SOURCE	Search...

Entry information

Entry name

PRDX3_HUMAN

Accession

Primary (citable) accession number: P30048
Secondary accession number(s): B2R7Z0 , P35690, Q0D2H1, Q13776, Q5T5V2, Q96HK4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	November 1, 1997
Last modified:	June 16, 2009
This is version 117 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)