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P00390 (GSHR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 194. 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 reductase, mitochondrial

Short name=GR
Short name=GRase
EC=1.8.1.7
Gene names
Name:GSR
Synonyms:GLUR, GRD1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length522 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Maintains high levels of reduced glutathione in the cytosol.

Catalytic activity

2 glutathione + NADP+ = glutathione disulfide + NADPH.

Cofactor

Binds 1 FAD per subunit.

Subunit structure

Homodimer; disulfide-linked. Ref.14

Subcellular location

Isoform Mitochondrial: Mitochondrion.

Isoform Cytoplasmic: Cytoplasm.

Domain

Each subunit can be divided into 4 domains that are consecutive along the polypeptide chain. Domains 1 and 2 bind FAD and NADPH, respectively. Domain 4 forms the interface.

Miscellaneous

The active site is a redox-active disulfide bond.

Sequence similarities

Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.

Sequence caution

The sequence AAP88037.1 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 5 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]
Isoform Mitochondrial (identifier: P00390-1)

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 Cytoplasmic (identifier: P00390-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-43: Missing.
Note: Produced by alternative initiation of isoform Mitochondrial.
Isoform 2 (identifier: P00390-3)

Also known as: delta8;

The sequence of this isoform differs from the canonical sequence as follows:
     266-294: Missing.
Isoform 3 (identifier: P00390-4)

Also known as: delta9;

The sequence of this isoform differs from the canonical sequence as follows:
     295-347: Missing.
Note: Expressed at very high levels in peripheral blood.
Isoform 4 (identifier: P00390-5)

Also known as: delta8+9;

The sequence of this isoform differs from the canonical sequence as follows:
     266-294: Missing.
     295-347: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 4343Mitochondrion Potential
Chain44 – 522479Glutathione reductase, mitochondrial
PRO_0000030276

Regions

Nucleotide binding94 – 1029FAD

Sites

Active site5111Proton acceptor

Amino acid modifications

Modified residue971N6-acetyllysine By similarity
Disulfide bond102 ↔ 107Redox-active Ref.14
Disulfide bond134Interchain Ref.14

Natural variations

Alternative sequence1 – 4343Missing in isoform Cytoplasmic.
VSP_018972
Alternative sequence266 – 29429Missing in isoform 2 and isoform 4.
VSP_042908
Alternative sequence295 – 34753Missing in isoform 3 and isoform 4.
VSP_042909
Natural variant1531R → C. Ref.3
Corresponds to variant rs8190955 [ dbSNP | Ensembl ].
VAR_019079
Natural variant2321G → R.
Corresponds to variant rs8190976 [ dbSNP | Ensembl ].
VAR_051775
Natural variant2321G → S. Ref.3
Corresponds to variant rs8190976 [ dbSNP | Ensembl ].
VAR_019080
Natural variant2611I → V. Ref.3
Corresponds to variant rs8190997 [ dbSNP | Ensembl ].
VAR_019081
Natural variant2971E → D. Ref.3
Corresponds to variant rs8191004 [ dbSNP | Ensembl ].
VAR_019082
Natural variant3141P → H.
Corresponds to variant rs2020916 [ dbSNP | Ensembl ].
VAR_014554

Secondary structure

....................................................................................... 522
Helix Strand Turn

Details...

Sequences

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

Last modified July 11, 2001. Version 2.
Checksum: DD8E2BA9D6E3757B

FASTA52256,257
        10         20         30         40         50         60 
MALLPRALSA GAGPSWRRAA RAFRGFLLLL PEPAALTRAL SRAMACRQEP QPQGPPPAAG 

        70         80         90        100        110        120 
AVASYDYLVI GGGSGGLASA RRAAELGARA AVVESHKLGG TCVNVGCVPK KVMWNTAVHS 

       130        140        150        160        170        180 
EFMHDHADYG FPSCEGKFNW RVIKEKRDAY VSRLNAIYQN NLTKSHIEII RGHAAFTSDP 

       190        200        210        220        230        240 
KPTIEVSGKK YTAPHILIAT GGMPSTPHES QIPGASLGIT SDGFFQLEEL PGRSVIVGAG 

       250        260        270        280        290        300 
YIAVEMAGIL SALGSKTSLM IRHDKVLRSF DSMISTNCTE ELENAGVEVL KFSQVKEVKK 

       310        320        330        340        350        360 
TLSGLEVSMV TAVPGRLPVM TMIPDVDCLL WAIGRVPNTK DLSLNKLGIQ TDDKGHIIVD 

       370        380        390        400        410        420 
EFQNTNVKGI YAVGDVCGKA LLTPVAIAAG RKLAHRLFEY KEDSKLDYNN IPTVVFSHPP 

       430        440        450        460        470        480 
IGTVGLTEDE AIHKYGIENV KTYSTSFTPM YHAVTKRKTK CVMKMVCANK EEKVVGIHMQ 

       490        500        510        520 
GLGCDEMLQG FAVAVKMGAT KADFDNTVAI HPTSSEELVT LR 

« Hide

Isoform Cytoplasmic [UniParc].

Checksum: 3C0A194C96E880E7
Show »

FASTA47951,701
Isoform 2 (delta8) [UniParc].

Checksum: EFBA71DCDCFF1529
Show »

FASTA49353,027
Isoform 3 (delta9) [UniParc].

Checksum: 0AD475B02A87C63E
Show »

FASTA46950,497
Isoform 4 (delta8+9) [UniParc].

Checksum: 793E0A9F8706B1B5
Show »

FASTA44047,267

References

« Hide 'large scale' references
[1]"Cloning and sequencing of mammalian glutathione reductase cDNA."
Tutic M., Lu X.A., Schirmer R.H., Werner D.
Eur. J. Biochem. 188:523-528(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYTOPLASMIC).
Tissue: Placenta.
[2]"Structural organization of the human glutathione reductase (GSR) gene: determination of correct cDNA sequence and identification of a mitochondrial leader sequence."
Kelner M.J., Montoya M.A.
Biochem. Biophys. Res. Commun. 269:366-368(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM MITOCHONDRIAL), ALTERNATIVE INITIATION.
[3]NIEHS SNPs program
Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-153; SER-232; VAL-261 AND ASP-297.
[4]"Expression of glutathione reductase splice variants in human tissues."
Satoh N., Watanabe N., Kanda A., Sugaya-Fukazawa M., Hisatomi H.
Biochem. Genet. 48:816-821(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[5]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]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. expand/collapse author list , 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].
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MITOCHONDRIAL).
Tissue: Lung.
[8]"Glutathione reductase from human erythrocytes. The sequences of the NADPH domain and of the interface domain."
Krauth-Siegel R.L., Blatterspiel R., Saleh M., Schiltz E., Schirmer R.H., Untucht-Grau R.
Eur. J. Biochem. 121:259-267(1982) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 45-522.
[9]"Glutathione reductase from human erythrocytes. Isolation of the enzyme and sequence analysis of the redox-active peptide."
Krohne-Ehrich G., Schirmer R.H., Untucht-Grau R.
Eur. J. Biochem. 80:65-71(1977) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 98-110.
Tissue: Erythrocyte.
[10]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"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].
[12]"Three-dimensional structure of glutathione reductase at 2-A resolution."
Thieme R., Pai E.F., Schirmer R.H., Schulz G.E.
J. Mol. Biol. 152:763-782(1981) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2 ANGSTROMS) OF 45-522.
[13]"Refined structure of glutathione reductase at 1.54-A resolution."
Karplus P.A., Schulz G.E.
J. Mol. Biol. 195:701-729(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 45-522.
[14]"Kinetics and crystallographic analysis of human glutathione reductase in complex with a xanthene inhibitor."
Savvides S.N., Karplus P.A.
J. Biol. Chem. 271:8101-8107(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 62-522, DISULFIDE BONDS.
[15]"Glutathione reductase turned into trypanothione reductase: structural analysis of an engineered change in substrate specificity."
Stoll V.S., Simpson S.J., Krauth-Siegel R.L., Walsh C.T., Pai E.F.
Biochemistry 36:6437-6447(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 62-522.
[16]"Enzyme inactivation through sulfhydryl oxidation by physiologic NO-carriers."
Becker K., Savvides S.N., Keese M., Schirmer R.H., Karplus P.A.
Nat. Struct. Biol. 5:267-271(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 62-522.
+Additional computationally mapped references.

Web resources

NIEHS-SNPs
Wikipedia

Glutathione reductase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X15722 mRNA. Translation: CAA33744.1.
AF228703 Genomic DNA. Translation: AAF37572.1.
AF228703 Genomic DNA. Translation: AAF37573.1.
AF228704 mRNA. Translation: AAF37574.1.
AY338490 Genomic DNA. Translation: AAP88037.1. Different initiation.
AB519179 mRNA. Translation: BAI43437.1.
AB519180 mRNA. Translation: BAI43438.1.
AB519181 mRNA. Translation: BAI43439.1.
AC009314 Genomic DNA. No translation available.
AC103959 Genomic DNA. No translation available.
AF215848 Genomic DNA. No translation available.
CH471080 Genomic DNA. Translation: EAW63443.1.
CH471080 Genomic DNA. Translation: EAW63445.1.
BC069244 mRNA. Translation: AAH69244.1.
CCDSCCDS34877.1. [P00390-1]
CCDS56530.1. [P00390-5]
CCDS56531.1. [P00390-3]
CCDS56532.1. [P00390-4]
PIRRDHUU. S08979.
RefSeqNP_000628.2. NM_000637.3. [P00390-1]
NP_001182031.1. NM_001195102.1. [P00390-3]
NP_001182032.1. NM_001195103.1. [P00390-4]
NP_001182033.1. NM_001195104.1. [P00390-5]
UniGeneHs.271510.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ALGNMR-A480-503[»]
1BWCX-ray2.10A45-522[»]
1DNCX-ray1.70A45-522[»]
1GRAX-ray2.00A45-522[»]
1GRBX-ray1.85A45-522[»]
1GREX-ray2.00A45-522[»]
1GRFX-ray2.00A45-522[»]
1GRGX-ray2.00A45-522[»]
1GRHX-ray3.00A45-522[»]
1GRTX-ray2.30A45-522[»]
1GSNX-ray1.70A45-522[»]
1K4QX-ray1.90A62-522[»]
1XANX-ray2.00A62-522[»]
2AAQX-ray2.60A44-522[»]
2GH5X-ray1.70A/B45-522[»]
2GRTX-ray2.70A62-522[»]
3DJGX-ray1.80X59-522[»]
3DJJX-ray1.10A45-522[»]
3DK4X-ray1.20A45-522[»]
3DK8X-ray1.10A45-522[»]
3DK9X-ray0.95A45-522[»]
3GRSX-ray1.54A45-522[»]
3GRTX-ray2.50A62-522[»]
3SQPX-ray2.21A/B45-522[»]
4GR1X-ray2.40A45-522[»]
4GRTX-ray2.80A62-522[»]
5GRTX-ray2.40A62-522[»]
ProteinModelPortalP00390.
SMRP00390. Positions 61-522.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109191. 26 interactions.
IntActP00390. 4 interactions.
MINTMINT-5000460.
STRING9606.ENSP00000221130.

Chemistry

BindingDBP00390.
ChEMBLCHEMBL2755.
DrugBankDB00262. Carmustine.
DB00143. Glutathione.
DB00157. NADH.
GuidetoPHARMACOLOGY2613.

PTM databases

PhosphoSiteP00390.

Polymorphism databases

DMDM14916998.

2D gel databases

REPRODUCTION-2DPAGEIPI00759575.

Proteomic databases

MaxQBP00390.
PaxDbP00390.
PRIDEP00390.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000221130; ENSP00000221130; ENSG00000104687. [P00390-1]
ENST00000414019; ENSP00000390065; ENSG00000104687. [P00390-2]
ENST00000537535; ENSP00000438845; ENSG00000104687. [P00390-5]
ENST00000541648; ENSP00000444559; ENSG00000104687. [P00390-4]
ENST00000546342; ENSP00000445516; ENSG00000104687. [P00390-3]
GeneID2936.
KEGGhsa:2936.
UCSCuc003xih.2. human. [P00390-1]
uc022ato.1. human. [P00390-4]
uc022atp.1. human. [P00390-3]
uc022atq.1. human. [P00390-5]

Organism-specific databases

CTD2936.
GeneCardsGC08M030535.
HGNCHGNC:4623. GSR.
HPACAB008632.
HPA001538.
MIM138300. gene+phenotype.
neXtProtNX_P00390.
Orphanet90030. Hemolytic anemia due to glutathione reductase deficiency.
PharmGKBPA29014.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1249.
HOGENOMHOG000276712.
HOVERGENHBG004959.
InParanoidP00390.
KOK00383.
OMAGTNSDGF.
OrthoDBEOG7HHWS0.
PhylomeDBP00390.
TreeFamTF105353.

Enzyme and pathway databases

BioCycMetaCyc:HS02602-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_120956. Cellular responses to stress.
SABIO-RKP00390.

Gene expression databases

ArrayExpressP00390.
BgeeP00390.
CleanExHS_GSR.
GenevestigatorP00390.

Family and domain databases

Gene3D3.30.390.30. 1 hit.
InterProIPR016156. FAD/NAD-linked_Rdtase_dimer.
IPR013027. FAD_pyr_nucl-diS_OxRdtase.
IPR006322. Glutathione_Rdtase_euk/bac.
IPR004099. Pyr_nucl-diS_OxRdtase_dimer.
IPR023753. Pyr_nucl-diS_OxRdtase_FAD/NAD.
IPR012999. Pyr_OxRdtase_I_AS.
IPR001327. Pyr_OxRdtase_NAD-bd_dom.
[Graphical view]
PfamPF00070. Pyr_redox. 1 hit.
PF07992. Pyr_redox_2. 1 hit.
PF02852. Pyr_redox_dim. 1 hit.
[Graphical view]
PRINTSPR00368. FADPNR.
SUPFAMSSF55424. SSF55424. 1 hit.
TIGRFAMsTIGR01421. gluta_reduc_1. 1 hit.
PROSITEPS00076. PYRIDINE_REDOX_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP00390.
GeneWikiGlutathione_reductase.
GenomeRNAi2936.
NextBio11635.
PROP00390.
SOURCESearch...

Entry information

Entry nameGSHR_HUMAN
AccessionPrimary (citable) accession number: P00390
Secondary accession number(s): C8KIL8 expand/collapse secondary AC list , C8KIL9, C8KIM0, D3DSV3, Q7Z5C9, Q9NP63
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 11, 2001
Last modified: July 9, 2014
This is version 194 of the entry and version 2 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 8

Human chromosome 8: entries, gene names and cross-references to MIM