P30048 (PRDX3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thioredoxin-dependent peroxide reductase, mitochondrial
EC=1.11.1.15

Alternative name(s):
Antioxidant protein 1
Short name=AOP-1
HBC189
Peroxiredoxin III
Short name=Prx-III
Peroxiredoxin-3
Protein MER5 homolog

Gene names

Name:	PRDX3
Synonyms:	AOP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.12
Catalytic activity	2 R'-SH + ROOH = R'-S-S-R' + H2O + ROH.
Subunit structure	Dodecameric ring assembled from homodimeric units; disulfide-linked, upon oxidation. The rings have an approximate diameter of 150 A and a central hole of 70 A. 3-5% of the rings are interlocked by pairs. Binds MAP3K13. Interacts with NEK6. Interacts with LRRK2. Ref.12 Ref.13 Ref.15 Ref.17
Subcellular location	Mitochondrion.
Post-translational modification	Phosphorylated by LRRK2; phosphorylation reduces perodixase activity. Ref.17
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	Acetylation Disulfide bond Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	hydrogen peroxide catabolic process Inferred from mutant phenotype PubMed 18195003. Source: UniProtKB maternal placenta development Inferred from electronic annotation. Source: Compara mitochondrion organization Inferred from mutant phenotype PubMed 12011429. Source: UniProtKB myeloid cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of apoptotic process Inferred from mutant phenotype PubMed 18262354. Source: UniProtKB negative regulation of kinase activity Inferred from direct assay PubMed 18205602. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Inferred from direct assay Ref.12. Source: UniProtKB positive regulation of cell proliferation Inferred from direct assay PubMed 12011429. Source: UniProtKB regulation of mitochondrial membrane potential Inferred from mutant phenotype PubMed 12011429. Source: UniProtKB response to lipopolysaccharide Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	early endosome Inferred from direct assay PubMed 15750338. Source: UniProtKB mitochondrion Inferred from direct assay PubMed 17893648PubMed 18262354. Source: UniProtKB
Molecular_function	alkyl hydroperoxide reductase activity Non-traceable author statement Ref.1. Source: UniProtKB cysteine-type endopeptidase inhibitor activity involved in apoptotic process Inferred from mutant phenotype PubMed 18262354. Source: UniProtKB peroxidase activity Inferred from electronic annotation. Source: UniProtKB-KW peroxiredoxin activity Inferred from electronic annotation. Source: EC
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.9
	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
	Modified residue	91	1	N6-acetyllysine Ref.14
	Modified residue	146	1	Phosphothreonine Probable
	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	170	1	R → Q. Corresponds to variant rs11554902 [ dbSNP | Ensembl ].		VAR_059546
	Natural variant	218	1	A → T. Ref.5		VAR_025053
	Natural variant	234	1	T → I. Ref.5 Corresponds to variant rs35697338 [ dbSNP | Ensembl ].		VAR_025054
Experimental info
	Mutagenesis	146	1	T → A: Impairs phosphorylation. Ref.17
	Sequence conflict	31	1	R → W in AAH08435. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	P30048 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow, Skeletal muscle, Testis, Urinary bladder and Uterus.
[9]	"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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 63-72. Tissue: Liver.
[10]	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.
[11]	"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] [Europe PMC] [Abstract] Cited for: OVEROXIDATION AT CYS-108.
[12]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAP3K13.
[13]	"Reconstitution of the mitochondrial PrxIII antioxidant defence pathway: general properties and factors affecting PrxIII activity and oligomeric state." Cao Z., Bhella D., Lindsay J.G. J. Mol. Biol. 372:1022-1033(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[14]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-91, MASS SPECTROMETRY.
[15]	"Characterization of hNek6 interactome reveals an important role for its short N-terminal domain and colocalization with proteins at the centrosome." Vaz Meirelles G., Ferreira Lanza D.C., da Silva J.C., Santana Bernachi J., Paes Leme A.F., Kobarg J. J. Proteome Res. 9:6298-6316(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NEK6.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death." Angeles D.C., Gan B.H., Onstead L., Zhao Y., Lim K.L., Dachsel J., Melrose H., Farrer M., Wszolek Z.K., Dickson D.W., Tan E.K. Hum. Mutat. 32:1390-1397(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LRRK2, PHOSPHORYLATION AT THR-146, MUTAGENESIS OF THR-146.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. CH471066 Genomic DNA. Translation: EAW49399.1. 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. NM_006793.2. NP_054817.2. NM_014098.2.
UniGene	Hs.523302. Hs.604267.
3D structure databases
ProteinModelPortal	P30048.
ModBase	Search...
Protein-protein interaction databases
IntAct	P30048. 33 interactions.
STRING	9606.ENSP00000298510.
Protein family/group databases
PeroxiBase	4492. Hs2CysPrx03.
PTM databases
PhosphoSite	P30048.
Polymorphism databases
DMDM	2507171.
2D gel databases
OGP	P30048.
SWISS-2DPAGE	P30048.
UCD-2DPAGE	P30048.
Proteomic databases
PaxDb	P30048.
PeptideAtlas	P30048.
PRIDE	P30048.
Protocols and materials databases
DNASU	10935.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000298510; ENSP00000298510; ENSG00000165672.
GeneID	10935.
KEGG	hsa:10935.
UCSC	uc001lec.3. human.
Organism-specific databases
CTD	10935.
GeneCards	GC10M120917.
H-InvDB	HIX0035477.
HGNC	HGNC:9354. PRDX3.
HPA	CAB008656.
MIM	604769. gene.
neXtProt	NX_P30048.
PharmGKB	PA33724.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0450.
HOVERGEN	HBG000286.
InParanoid	P30048.
KO	K03386.
OMA	FAHKAWH.
OrthoDB	EOG4S7JQS.
PhylomeDB	P30048.
Gene expression databases
ArrayExpress	P30048.
Bgee	P30048.
CleanEx	HS_PRDX3.
Genevestigator	P30048.
GermOnline	ENSG00000165672. Homo sapiens.
Family and domain databases
Gene3D	3.40.30.10. 1 hit.
InterPro	IPR000866. AhpC/TSA. IPR024706. Peroxiredoxin_AhpC-typ. IPR019479. Peroxiredoxin_C. IPR012336. Thioredoxin-like_fold. [Graphical view]
Pfam	PF10417. 1-cysPrx_C. 1 hit. PF00578. AhpC-TSA. 1 hit. [Graphical view]
PIRSF	PIRSF000239. AHPC. 1 hit.
SUPFAM	SSF52833. Thiordxn-like_fd. 1 hit.
PROSITE	PS51352. THIOREDOXIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PRDX3. human.
GenomeRNAi	10935.
NextBio	41537.
SOURCE	Search...

Entry information

Entry name

PRDX3_HUMAN

Accession

Primary (citable) accession number: P30048
Secondary accession number(s): B2R7Z0 , D3DRC9, P35690, Q0D2H1, Q13776, Q5T5V2, Q96HK4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 160 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.