P07203 (GPX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutathione peroxidase 1
Short name=GPx-1
Short name=GSHPx-1
EC=1.11.1.9

Alternative name(s):
Cellular glutathione peroxidase

Gene names

Name:

GPX1

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	203 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Protects the hemoglobin in erythrocytes from oxidative breakdown.
Catalytic activity	2 glutathione + H2O2 = glutathione disulfide + 2 H2O.
Subunit structure	Homotetramer. Interacts with MIEN1.
Subcellular location	Cytoplasm.
Post-translational modification	During periods of oxidative stress, Sec-49 may react with a superoxide radical, irreversibly lose hydroselenide and be converted to dehydroalanine By similarity.
Sequence similarities	Belongs to the glutathione peroxidase family.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism Selenocysteine
Molecular function	Oxidoreductase Peroxidase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	UV protection Inferred from mutant phenotype PubMed 17097614. Source: BHF-UCL angiogenesis involved in wound healing Inferred from electronic annotation. Source: Compara arachidonic acid metabolic process Traceable author statement. Source: Reactome blood vessel endothelial cell migration Inferred from electronic annotation. Source: Compara cell redox homeostasis Inferred from direct assay PubMed 12829378. Source: BHF-UCL endothelial cell development Inferred from electronic annotation. Source: Compara fat cell differentiation Inferred from electronic annotation. Source: Compara glutathione metabolic process Inferred from direct assay PubMed 12829378. Source: BHF-UCL heart contraction Inferred from mutant phenotype PubMed 14573732. Source: BHF-UCL hydrogen peroxide catabolic process Inferred from direct assay PubMed 15203190. Source: BHF-UCL induction of apoptosis Inferred from electronic annotation. Source: Compara interaction with symbiont Inferred from electronic annotation. Source: Compara intrinsic apoptotic signaling pathway in response to oxidative stress Inferred from electronic annotation. Source: Compara lipoxygenase pathway Traceable author statement. Source: Reactome myoblast proliferation Inferred from electronic annotation. Source: Compara myotube differentiation Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from mutant phenotype PubMed 12221075. Source: BHF-UCL negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from mutant phenotype PubMed 12221075. Source: BHF-UCL negative regulation of inflammatory response to antigenic stimulus Inferred from electronic annotation. Source: Compara positive regulation of protein kinase B signaling cascade Inferred from electronic annotation. Source: Compara protein oxidation Inferred from electronic annotation. Source: Compara purine nucleobase metabolic process Traceable author statement. Source: Reactome purine nucleotide catabolic process Traceable author statement. Source: Reactome regulation of gene expression, epigenetic Inferred from direct assay PubMed 16132718. Source: BHF-UCL regulation of mammary gland epithelial cell proliferation Inferred from mutant phenotype PubMed 16945136. Source: BHF-UCL regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara regulation of proteasomal protein catabolic process Inferred from direct assay PubMed 12751788. Source: BHF-UCL release of cytochrome c from mitochondria Inferred from mutant phenotype PubMed 12221075. Source: BHF-UCL response to gamma radiation Inferred from electronic annotation. Source: Compara response to hydroperoxide Inferred from electronic annotation. Source: Compara response to selenium ion Inferred from mutant phenotype PubMed 12810669. Source: BHF-UCL response to symbiotic bacterium Inferred from electronic annotation. Source: Compara response to toxic substance Inferred from electronic annotation. Source: Compara response to xenobiotic stimulus Inferred from electronic annotation. Source: Compara sensory perception of sound Inferred from electronic annotation. Source: Compara skeletal muscle fiber development Inferred from electronic annotation. Source: Compara skeletal muscle tissue regeneration Inferred from electronic annotation. Source: Compara temperature homeostasis Inferred from electronic annotation. Source: Compara triglyceride metabolic process Inferred from electronic annotation. Source: Compara vasodilation Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome mitochondrion Inferred from direct assay PubMed 10833429. Source: BHF-UCL
Molecular_function	endopeptidase inhibitor activity Inferred from direct assay PubMed 12751788. Source: BHF-UCL glutathione peroxidase activity Inferred from direct assay PubMed 12829378. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 203

203

Glutathione peroxidase 1

PRO_0000066610

Sites

Active site

49

1

Site

49

1

Subject to oxidation and hydroselenide loss to dehydroalanine By similarity

Amino acid modifications

Non-standard residue

49

1

Selenocysteine

Modified residue

148

1

N6-acetyllysine By similarity

Natural variations

Natural variant

5

1

R → P. Ref.6
Corresponds to variant rs8179169 [ dbSNP | Ensembl ].

VAR_020912

Natural variant

7 – 8

2

Missing.

VAR_020913

Natural variant

8

1

Missing. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.12 Ref.13

VAR_020914

Natural variant

194

1

A → T. Ref.6

VAR_020915

Natural variant

200

1

P → L Frequent polymorphism. Ref.6 Ref.11 Ref.13 Ref.14
Corresponds to variant rs1050450 [ dbSNP | Ensembl ].

VAR_007904

Experimental info

Sequence conflict

93

1

L → Q in CAA31992. Ref.3

Secondary structure

1

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203

Helix Strand Turn

Details...

Helix

16 – 18

3

Helix

32 – 35

4

Beta strand

38 – 45

8

Beta strand

47 – 49

3

Helix

52 – 66

15

Helix

67 – 69

3

Beta strand

71 – 77

7

Turn

82 – 85

4

Helix

89 – 91

3

Helix

92 – 98

7

Beta strand

108 – 112

5

Helix

124 – 132

9

Helix

147 – 149

3

Beta strand

152 – 154

3

Beta strand

166 – 169

4

Beta strand

175 – 179

5

Helix

185 – 188

4

Helix

189 – 196

8

Sequences

	Sequence		Length	Mass (Da)
	P07203 [UniParc]. Last modified November 2, 2010. Version 4. Checksum: 5DB11579C66FE8E5	FASTA	203	22,088
	10 20 30 40 50 60 MCAARLAAAA AAAQSVYAFS ARPLAGGEPV SLGSLRGKVL LIENVASLUG TTVRDYTQMN 70 80 90 100 110 120 ELQRRLGPRG LVVLGFPCNQ FGHQENAKNE EILNSLKYVR PGGGFEPNFM LFEKCEVNGA 130 140 150 160 170 180 GAHPLFAFLR EALPAPSDDA TALMTDPKLI TWSPVCRNDV AWNFEKFLVG PDGVPLRRYS 190 200 RRFQTIDIEP DIEALLSQGP SCA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA sequence coding for human glutathione peroxidase." Sukenaga Y., Ishida K., Takeda T., Takagi K. Nucleic Acids Res. 15:7178-7178(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT 7-ALA-ALA-8 DEL.
[2]	"Nucleotide sequence of a human gene for glutathione peroxidase." Ishida K., Morino T., Takagi K., Sukenaga Y. Nucleic Acids Res. 15:10051-10051(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT 7-ALA-ALA-8 DEL.
[3]	"Sequence of a cDNA coding for human glutathione peroxidase confirms TGA encodes active site selenocysteine." Mullenbach G.T., Tabrizi A., Irvine B.D., Bell G.I., Hallewell R.A. Nucleic Acids Res. 15:5484-5484(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT 7-ALA-ALA-8 DEL. Tissue: Kidney.
[4]	"Isolation and chromosomal localization of the human glutathione peroxidase gene." Chada S., le Beau M.M., Casey L., Newburger P.E. Genomics 6:268-271(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT 7-ALA-ALA-8 DEL.
[5]	"Structure and function of the 5'-flanking sequence of the human cytosolic selenium-dependent glutathione peroxidase gene (hgpx1)." Moscow J.A., Morrow C.S., He R., Mullenbach G.T., Cowan K.H. J. Biol. Chem. 267:5949-5958(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ALA-8 DEL.
[6]	NIEHS SNPs program Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PRO-5; THR-194 AND LEU-200.
[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: Placenta.
[9]	"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].
[10]	"Crystal structure of the selenocysteine to glycine mutant of human glutathione peroxidase 1." Structural genomics consortium (SGC) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 14-198.
[11]	"Low yield of polymorphisms from EST blast searching: analysis of genes related to oxidative stress and verification of the P197L polymorphism in GPX1." Forsberg L., de Faire U., Morgenstern R. Hum. Mutat. 13:294-300(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LEU-200.
[12]	"Association between the GCG polymorphism of the selenium dependent GPX1 gene and the risk of young onset prostate cancer." Kote-Jarai Z., Durocher F., Edwards S.M., Hamoudi R., Jackson R.A., Ardern-Jones A., Murkin A., Dearnaley D.P., Kirby R., Houlston R., Easton D.F., Eeles R. Prostate Cancer Prostatic Dis. 5:189-192(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ALA-8 DEL AND 7-ALA-ALA-8 DEL.
[13]	"Functional variants in the glutathione peroxidase-1 (GPx-1) gene are associated with increased intima-media thickness of carotid arteries and risk of macrovascular diseases in Japanese type 2 diabetic patients." Hamanishi T., Furuta H., Kato H., Doi A., Tamai M., Shimomura H., Sakagashira S., Nishi M., Sasaki H., Sanke T., Nanjo K. Diabetes 53:2455-2460(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ALA-8 DEL AND LEU-200.
[14]	"Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant." Ichimura Y., Habuchi T., Tsuchiya N., Wang L., Oyama C., Sato K., Nishiyama H., Ogawa O., Kato T. J. Urol. 172:728-732(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LEU-200.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Wikipedia

Glutathione peroxidase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y00433 mRNA. Translation: CAA68491.1.
Y00483 Genomic DNA. Translation: CAB37833.1.
X13709 mRNA. Translation: CAA31992.1.
X13710 mRNA. Translation: CAA31993.1.
M21304 mRNA. Translation: AAA75389.2.
M83094 Genomic DNA. Translation: AAA67540.2.
AY327818 Genomic DNA. Translation: AAP80181.1.
AC121247 Genomic DNA. No translation available.
BC000742 mRNA. Translation: AAH00742.3.

IPI

IPI00927606.

PIR

OPHUE. A42152.

RefSeq

NP_000572.2. NM_000581.2.
NP_958799.1. NM_201397.1.

UniGene

Hs.76686.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2F8A	X-ray	1.50	A/B	14-196	[»]

ProteinModelPortal

P07203.

SMR

P07203. Positions 14-197.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000407375.

Protein family/group databases

PeroxiBase

3600. HsGPx01-A.

PTM databases

PhosphoSite

P07203.

Polymorphism databases

DMDM

311033481.

2D gel databases

OGP

P07203.

SWISS-2DPAGE

P07203.

Proteomic databases

PaxDb

P07203.

PRIDE

P07203.

Protocols and materials databases

DNASU

2876.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000419783; ENSP00000407375; ENSG00000233276.

GeneID

2876.

KEGG

hsa:2876.

UCSC

uc021wxw.1. human.

Organism-specific databases

CTD

2876.

GeneCards

GC03M049369.

H-InvDB

HIX0003298.

HGNC

HGNC:4553. GPX1.

HPA

CAB011582.

MIM

138320. gene+phenotype.

neXtProt

NX_P07203.

PharmGKB

PA28949.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0386.

HOGENOM

HOG000277055.

HOVERGEN

HBG004333.

InParanoid

P07203.

KO

K00432.

OMA

CEVNGAG.

OrthoDB

EOG4SBF08.

PhylomeDB

P07203.

Enzyme and pathway databases

BioCyc

MetaCyc:HS00019-MONOMER.

Reactome

REACT_111217. Metabolism.

Gene expression databases

Bgee

P07203.

CleanEx

HS_GPX1.

Genevestigator

P07203.

GermOnline

ENSG00000211447. 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

GPX1. human.

DrugBank

DB00143. Glutathione.

EvolutionaryTrace

P07203.

GenomeRNAi

2876.

NextBio

11353.

SOURCE

Search...

Entry information

Entry name

GPX1_HUMAN

Accession

Primary (citable) accession number: P07203
Secondary accession number(s): Q7Z5H1, Q9BW12

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	November 2, 2010
Last modified:	May 29, 2013
This is version 158 of the entry and version 4 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.