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P07203 (GPX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 168. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length203 AA.
Sequence statusComplete.
Protein existenceEvidence 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 componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
Selenocysteine
   Molecular functionOxidoreductase
Peroxidase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processUV protection

Inferred from mutant phenotype PubMed 17097614. Source: BHF-UCL

aging

Inferred from electronic annotation. Source: Ensembl

angiogenesis involved in wound healing

Inferred from electronic annotation. Source: Ensembl

arachidonic acid metabolic process

Traceable author statement. Source: Reactome

blood vessel endothelial cell migration

Inferred from electronic annotation. Source: Ensembl

cell redox homeostasis

Inferred from direct assay PubMed 12829378. Source: BHF-UCL

endothelial cell development

Inferred from electronic annotation. Source: Ensembl

fat cell differentiation

Inferred from electronic annotation. Source: Ensembl

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

interaction with symbiont

Inferred from electronic annotation. Source: Ensembl

intrinsic apoptotic signaling pathway in response to oxidative stress

Inferred from electronic annotation. Source: Ensembl

lipoxygenase pathway

Traceable author statement. Source: Reactome

myoblast proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from mutant phenotype PubMed 12221075. Source: BHF-UCL

negative regulation of extrinsic apoptotic signaling pathway via death domain receptors

Inferred from mutant phenotype PubMed 12221075. Source: BHF-UCL

negative regulation of inflammatory response to antigenic stimulus

Inferred from electronic annotation. Source: Ensembl

negative regulation of intrinsic apoptotic signaling pathway in response to oxidative stress

Inferred from electronic annotation. Source: Ensembl

negative regulation of release of cytochrome c from mitochondria

Inferred from mutant phenotype PubMed 12221075. Source: BHF-UCL

nucleobase-containing small molecule metabolic process

Traceable author statement. Source: Reactome

positive regulation of protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

protein oxidation

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

regulation of proteasomal protein catabolic process

Inferred from direct assay PubMed 12751788. Source: BHF-UCL

response to estradiol

Inferred from electronic annotation. Source: Ensembl

response to folic acid

Inferred from electronic annotation. Source: Ensembl

response to gamma radiation

Inferred from electronic annotation. Source: Ensembl

response to glucose

Inferred from electronic annotation. Source: Ensembl

response to hydrogen peroxide

Inferred from mutant phenotype PubMed 12829378. Source: BHF-UCL

response to lipid hydroperoxide

Inferred from electronic annotation. Source: Ensembl

response to nicotine

Inferred from electronic annotation. Source: Ensembl

response to selenium ion

Inferred from mutant phenotype PubMed 12810669. Source: BHF-UCL

response to symbiotic bacterium

Inferred from electronic annotation. Source: Ensembl

response to toxic substance

Inferred from electronic annotation. Source: Ensembl

response to xenobiotic stimulus

Inferred from electronic annotation. Source: Ensembl

sensory perception of sound

Inferred from electronic annotation. Source: Ensembl

skeletal muscle fiber development

Inferred from electronic annotation. Source: Ensembl

skeletal muscle tissue regeneration

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

temperature homeostasis

Inferred from electronic annotation. Source: Ensembl

triglyceride metabolic process

Inferred from electronic annotation. Source: Ensembl

vasodilation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 10833429. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

mitochondrial matrix

Traceable author statement. Source: Reactome

mitochondrion

Inferred from direct assay PubMed 10833429. Source: BHF-UCL

nucleus

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionSH3 domain binding

Inferred from physical interaction PubMed 12893824. Source: BHF-UCL

glutathione binding

Inferred from electronic annotation. Source: Ensembl

glutathione peroxidase activity

Inferred from direct assay PubMed 12829378. Source: BHF-UCL

phospholipid-hydroperoxide glutathione peroxidase activity

Inferred from electronic annotation. Source: Ensembl

selenium binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P07203-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P07203-2)

The sequence of this isoform differs from the canonical sequence as follows:
     85-98: ENAKNEEILNSLKY → VRRAERGGAGADVQ
     99-203: Missing.
Note: Gene prediction based on EST data.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 203203Glutathione peroxidase 1
PRO_0000066610

Sites

Active site491
Site491Subject to oxidation and hydroselenide loss to dehydroalanine By similarity

Amino acid modifications

Non-standard residue491Selenocysteine
Modified residue881N6-acetyllysine; alternate By similarity
Modified residue881N6-succinyllysine; alternate By similarity
Modified residue1141N6-acetyllysine; alternate By similarity
Modified residue1141N6-succinyllysine; alternate By similarity
Modified residue1481N6-acetyllysine; alternate By similarity
Modified residue1481N6-succinyllysine; alternate By similarity

Natural variations

Alternative sequence85 – 9814ENAKN…NSLKY → VRRAERGGAGADVQ in isoform 2.
VSP_047369
Alternative sequence99 – 203105Missing in isoform 2.
VSP_047370
Natural variant51R → P. Ref.6
Corresponds to variant rs8179169 [ dbSNP | Ensembl ].
VAR_020912
Natural variant7 – 82Missing.
VAR_020913
Natural variant81Missing. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.12 Ref.13
VAR_020914
Natural variant1941A → T. Ref.6
Corresponds to variant rs6446261 [ dbSNP | Ensembl ].
VAR_020915
Natural variant2001P → L Frequent polymorphism. Ref.6 Ref.11 Ref.13 Ref.14
Corresponds to variant rs1050450 [ dbSNP | Ensembl ].
VAR_007904

Experimental info

Sequence conflict931L → Q in CAA31992. Ref.3

Secondary structure

.................................. 203
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 2, 2010. Version 4.
Checksum: 5DB11579C66FE8E5

FASTA20322,088
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 9AD713E53537E4A0
Show »

FASTA9810,289

References

« Hide '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] (ISOFORM 1), 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] (ISOFORM 1), 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] (ISOFORM 1), 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] (ISOFORM 1), 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] (ISOFORM 1), VARIANT ALA-8 DEL.
[6]NIEHS SNPs program
Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), 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. expand/collapse author list , 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] (ISOFORM 1).
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.
PIROPHUE. A42152.
RefSeqNP_000572.2. NM_000581.2.
NP_958799.1. NM_201397.1.
UniGeneHs.76686.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2F8AX-ray1.50A/B1-198[»]
ProteinModelPortalP07203.
SMRP07203. Positions 14-197.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109134. 7 interactions.
IntActP07203. 1 interaction.
STRING9606.ENSP00000407375.

Chemistry

ChEMBLCHEMBL2163186.
DrugBankDB00143. Glutathione.

Protein family/group databases

PeroxiBase3600. HsGPx01-A.

PTM databases

PhosphoSiteP07203.

Polymorphism databases

DMDM311033481.

2D gel databases

OGPP07203.
SWISS-2DPAGEP07203.

Proteomic databases

PaxDbP07203.
PRIDEP07203.

Protocols and materials databases

DNASU2876.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000419349; ENSP00000391316; ENSG00000233276. [P07203-2]
ENST00000419783; ENSP00000407375; ENSG00000233276. [P07203-1]
GeneID2876.
KEGGhsa:2876.
UCSCuc021wxw.1. human. [P07203-1]

Organism-specific databases

CTD2876.
GeneCardsGC03M049369.
H-InvDBHIX0003298.
HGNCHGNC:4553. GPX1.
HPACAB011582.
HPA044758.
MIM138320. gene+phenotype.
neXtProtNX_P07203.
PharmGKBPA28949.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0386.
HOGENOMHOG000277055.
HOVERGENHBG004333.
InParanoidP07203.
KOK00432.
OMACEVNGEK.
OrthoDBEOG7KQ23C.
PhylomeDBP07203.
TreeFamTF105318.

Enzyme and pathway databases

BioCycMetaCyc:HS00019-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_120956. Cellular responses to stress.

Gene expression databases

BgeeP07203.
CleanExHS_GPX1.
GenevestigatorP07203.

Family and domain databases

Gene3D3.40.30.10. 1 hit.
InterProIPR000889. Glutathione_peroxidase.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERPTHR11592. PTHR11592. 1 hit.
PfamPF00255. GSHPx. 1 hit.
[Graphical view]
PIRSFPIRSF000303. Glutathion_perox. 1 hit.
PRINTSPR01011. GLUTPROXDASE.
SUPFAMSSF52833. SSF52833. 1 hit.
PROSITEPS00460. GLUTATHIONE_PEROXID_1. 1 hit.
PS00763. GLUTATHIONE_PEROXID_2. 1 hit.
PS51355. GLUTATHIONE_PEROXID_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGPX1. human.
EvolutionaryTraceP07203.
GeneWikiGPX1.
GenomeRNAi2876.
NextBio11353.
PROP07203.
SOURCESearch...

Entry information

Entry nameGPX1_HUMAN
AccessionPrimary (citable) accession number: P07203
Secondary accession number(s): E9PAS1, Q7Z5H1, Q9BW12
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: November 2, 2010
Last modified: April 16, 2014
This is version 168 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM