P22352 (GPX3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutathione peroxidase 3
Short name=GPx-3
Short name=GSHPx-3
EC=1.11.1.9

Alternative name(s):
Extracellular glutathione peroxidase
Plasma glutathione peroxidase
Short name=GPx-P
Short name=GSHPx-P

Gene names

Name:	GPX3
Synonyms:	GPXP

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	226 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	Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione.
Catalytic activity	2 glutathione + H2O2 = glutathione disulfide + 2 H2O.
Subunit structure	Homotetramer.
Subcellular location	Secreted.
Tissue specificity	Secreted in plasma.
Post-translational modification	The N-terminus is blocked.
Sequence similarities	Belongs to the glutathione peroxidase family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism Selenocysteine
Domain	Signal
Molecular function	Oxidoreductase Peroxidase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	hydrogen peroxide catabolic process Traceable author statement PubMed 2491950. Source: UniProtKB protein homotetramerization Inferred from direct assay PubMed 3693360. Source: UniProtKB response to lipid hydroperoxide Traceable author statement PubMed 2491950. Source: UniProtKB
Cellular_component	extracellular space Inferred from direct assay Ref.9. Source: UniProtKB
Molecular_function	glutathione peroxidase activity Inferred from direct assay Ref.9PubMed 3693360. Source: UniProtKB selenium binding Inferred from direct assay PubMed 2491950PubMed 3693360. Source: UniProtKB transcription factor binding Traceable author statement Ref.4. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Potential

Chain

21 – 226

206

Glutathione peroxidase 3

PRO_0000013062

Sites

Active site

73

1

Amino acid modifications

Non-standard residue

73

1

Selenocysteine Ref.1

Natural variations

Natural variant

128

1

F → L. Ref.6
Corresponds to variant rs8177445 [ dbSNP | Ensembl ].

VAR_020943

Secondary structure

1

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226

Helix Strand Turn

Details...

Helix

40 – 42

3

Beta strand

44 – 47

4

Beta strand

53 – 55

3

Helix

56 – 59

4

Beta strand

62 – 69

8

Beta strand

71 – 73

3

Turn

74 – 77

4

Helix

78 – 89

12

Helix

90 – 92

3

Beta strand

94 – 100

7

Helix

112 – 114

3

Helix

115 – 121

7

Beta strand

131 – 135

5

Beta strand

140 – 142

3

Helix

147 – 155

9

Helix

166 – 168

3

Beta strand

185 – 188

4

Beta strand

194 – 198

5

Helix

204 – 223

20

Sequences

	Sequence		Length	Mass (Da)
	P22352 [UniParc]. Last modified February 26, 2008. Version 2. Checksum: A839E87A5CDB51A9	FASTA	226	25,552
	10 20 30 40 50 60 MARLLQASCL LSLLLAGFVS QSRGQEKSKM DCHGGISGTI YEYGALTIDG EEYIPFKQYA 70 80 90 100 110 120 GKYVLFVNVA SYUGLTGQYI ELNALQEELA PFGLVILGFP CNQFGKQEPG ENSEILPTLK 130 140 150 160 170 180 YVRPGGGFVP NFQLFEKGDV NGEKEQKFYT FLKNSCPPTS ELLGTSDRLF WEPMKVHDIR 190 200 210 220 WNFEKFLVGP DGIPIMRWHH RTTVSNVKMD ILSYMRRQAA LGVKRK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of human plasma glutathione peroxidase deduced from cDNA sequences." Takahashi K., Akasaka M., Yamamoto Y., Kobayashi C., Mizoguchi J., Koyama J. J. Biochem. 108:145-148(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Fetal liver and Placenta.
[2]	"Expression of plasma glutathione peroxidase in human liver in addition to kidney, heart, lung, and breast in humans and rodents." Chu F.-F., Esworthy R.S., Doroshow J.H., Doan K., Liu X.F. Blood 79:3233-3238(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[3]	Chu F.-F. Submitted (NOV-2010) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 73.
[4]	"The human plasma glutathione peroxidase-encoding gene: organization, sequence and localization to chromosome 5q32." Yoshimura S., Suemizu H., Taniguchi Y., Arimori K., Kawabe N., Moriuchi T. Gene 145:293-297(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Lymphocyte.
[5]	"Differential induction of extracellular glutathione peroxidase and nitric oxide synthase 2 in airways of healthy individuals exposed to 100% O(2) or cigarette smoke." Comhair S.A.A., Thomassen M.J., Erzurum S.C. Am. J. Respir. Cell Mol. Biol. 23:350-354(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	NIEHS SNPs program Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LEU-128.
[7]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] 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: Duodenum, Lung and Pancreas.
[9]	"Characterization and partial amino acid sequence of human plasma glutathione peroxidase." Esworthy R.S., Chu F.-F., Paxton R.J., Akman S., Doroshow J.H. Arch. Biochem. Biophys. 286:330-336(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 107-138 AND 148-175, CHARACTERIZATION.
[10]	"Crystal structure of human glutathione peroxidase 3 (selenocysteine to glycine mutant)." Structural genomics consortium (SGC) Submitted (SEP-2007) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 25-223.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Wikipedia

Glutathione peroxidase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D00632 mRNA. Translation: BAA00525.1.
X58295 mRNA. Translation: CAA41228.2.
D16360 Genomic DNA. Translation: BAA03862.1.
D16361 Genomic DNA. Translation: BAA03863.2.
D16362 Genomic DNA. Translation: BAA03864.1.
AF217787 mRNA. Translation: AAF43005.1.
AY310878 Genomic DNA. Translation: AAP50261.1.
AC008641 Genomic DNA. No translation available.
BC013601 mRNA. Translation: AAH13601.1.
BC035841 mRNA. Translation: AAH35841.1.
BC050378 mRNA. Translation: AAH50378.2.

IPI

IPI00026199.

PIR

JQ0476. I53822.

RefSeq

NP_002075.2. NM_002084.3.

UniGene

Hs.386793.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2R37	X-ray	1.85	A/B	25-223	[»]

ProteinModelPortal

P22352.

ModBase

Search...

Protein-protein interaction databases

IntAct

P22352. 6 interactions.

STRING

9606.ENSP00000373477.

Protein family/group databases

PeroxiBase

3602. HsGPx03.

Polymorphism databases

DMDM

172046796.

2D gel databases

REPRODUCTION-2DPAGE

IPI00026199.

SWISS-2DPAGE

P22352.

Proteomic databases

PaxDb

P22352.

PRIDE

P22352.

Protocols and materials databases

DNASU

2878.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000388825; ENSP00000373477; ENSG00000211445.

GeneID

2878.

KEGG

hsa:2878.

UCSC

uc021yga.1. human.

Organism-specific databases

CTD

2878.

GeneCards

GC05P150381.

H-InvDB

HIX0024803.

HGNC

HGNC:4555. GPX3.

MIM

138321. gene.

neXtProt

NX_P22352.

PharmGKB

PA28951.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0386.

HOGENOM

HOG000277055.

HOVERGEN

HBG004333.

InParanoid

P22352.

KO

K00432.

OMA

SNVKMDI.

OrthoDB

EOG4CRM10.

PhylomeDB

P22352.

Enzyme and pathway databases

BioCyc

MetaCyc:HS08224-MONOMER.

Gene expression databases

ArrayExpress

P22352.

Bgee

P22352.

CleanEx

HS_GPX3.

Genevestigator

P22352.

GermOnline

ENSG00000211445. Homo sapiens.

Family and domain databases

Gene3D

3.40.30.10. 1 hit.

InterPro

IPR000889. Glutathione_peroxidase.
IPR012336. Thioredoxin-like_fold.
[Graphical view]

PANTHER

PTHR11592. PTHR11592. 1 hit.

Pfam

PF00255. GSHPx. 1 hit.
[Graphical view]

PIRSF

PIRSF000303. Glutathion_perox. 1 hit.

PRINTS

PR01011. GLUTPROXDASE.

SUPFAM

SSF52833. Thiordxn-like_fd. 1 hit.

PROSITE

PS00460. GLUTATHIONE_PEROXID_1. 1 hit.
PS00763. GLUTATHIONE_PEROXID_2. 1 hit.
PS51355. GLUTATHIONE_PEROXID_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

GPX3. human.

DrugBank

DB00143. Glutathione.

EvolutionaryTrace

P22352.

GenomeRNAi

2878.

NextBio

11363.

SOURCE

Search...

Entry information

Entry name

GPX3_HUMAN

Accession

Primary (citable) accession number: P22352
Secondary accession number(s): O43787 , Q86W78, Q9NZ74, Q9UEL1

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	February 26, 2008
Last modified:	May 29, 2013
This is version 142 of the entry and version 2 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.