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UniProtKB/Swiss-Prot entry P00390


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name GSHR_HUMAN
Primary accession number P00390
Secondary accession numbers Q7Z5C9 Q9NP63
Integrated into Swiss-Prot on July 21, 1986
Sequence was last modified on July 11, 2001 (Sequence version 2)
Annotations were last modified on    July 22, 2008 (Entry version 129)
Name and origin of the protein
Protein name Glutathione reductase, mitochondrial [Precursor]
Synonyms GRase
GR
EC 1.8.1.7
Gene name
Name: GSR
Synonyms: GLUR, GRD1
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CYTOPLASMIC).
TISSUE=Placenta;
PubMed=2185014 [NCBI, ExPASy, EBI, Israel, Japan]
Tutic M., Lu X.A., Schirmer R.H., Werner D.;
"Cloning and sequencing of mammalian glutathione reductase cDNA.";
Eur. J. Biochem. 188:523-528(1990).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND ALTERNATIVE INITIATION.
DOI=10.1006/bbrc.2000.2267; PubMed=10708558 [NCBI, ExPASy, EBI, Israel, Japan]
Kelner M.J., Montoya M.A.;
"Structural organization of the human glutathione reductase (GSR) gene: determination of correct cDNA sequence and identification of a mitochondrial leader sequence.";
Biochem. Biophys. Res. Commun. 269:366-368(2000).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CYS-153; SER-232; VAL-261 AND ASP-297.
Rieder M.J., Livingston R.J., Daniels M.R., Chung M.-W., Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.;
"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature04406; PubMed=16421571 [NCBI, ExPASy, EBI, Israel, Japan]
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., 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.;
"DNA sequence and analysis of human chromosome 8.";
Nature 439:331-335(2006).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MITOCHONDRIAL).
TISSUE=Lung;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
PROTEIN SEQUENCE OF 45-522.
PubMed=7060551 [NCBI, ExPASy, EBI, Israel, Japan]
Krauth-Siegel R.L., Blatterspiel R., Saleh M., Schiltz E., Schirmer R.H., Untucht-Grau R.;
"Glutathione reductase from human erythrocytes. The sequences of the NADPH domain and of the interface domain.";
Eur. J. Biochem. 121:259-267(1982).
[7]
PROTEIN SEQUENCE OF 98-110.
TISSUE=Erythrocyte;
PubMed=923580 [NCBI, ExPASy, EBI, Israel, Japan]
Krohne-Ehrich G., Schirmer R.H., Untucht-Grau R.;
"Glutathione reductase from human erythrocytes. Isolation of the enzyme and sequence analysis of the redox-active peptide.";
Eur. J. Biochem. 80:65-71(1977).
[8]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-65, AND MASS SPECTROMETRY.
DOI=10.1038/nbt1046; PubMed=15592455 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
Nat. Biotechnol. 23:94-101(2005).
[9]
X-RAY CRYSTALLOGRAPHY (2 ANGSTROMS) OF 45-522.
DOI=10.1016/0022-2836(81)90126-1; PubMed=7334521 [NCBI, ExPASy, EBI, Israel, Japan]
Thieme R., Pai E.F., Schirmer R.H., Schulz G.E.;
"Three-dimensional structure of glutathione reductase at 2-A resolution.";
J. Mol. Biol. 152:763-782(1981).
[10]
X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 45-522.
DOI=10.1016/0022-2836(87)90191-4; PubMed=3656429 [NCBI, ExPASy, EBI, Israel, Japan]
Karplus P.A., Schulz G.E.;
"Refined structure of glutathione reductase at 1.54-A resolution.";
J. Mol. Biol. 195:701-729(1987).
[11]
X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 62-522, AND DISULFIDE BONDS.
DOI=10.1074/jbc.271.14.8101; PubMed=8626496 [NCBI, ExPASy, EBI, Israel, Japan]
Savvides S.N., Karplus P.A.;
"Kinetics and crystallographic analysis of human glutathione reductase in complex with a xanthene inhibitor.";
J. Biol. Chem. 271:8101-8107(1996).
[12]
X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 62-522.
DOI=10.1021/bi963074p; PubMed=9174360 [NCBI, ExPASy, EBI, Israel, Japan]
Stoll V.S., Simpson S.J., Krauth-Siegel R.L., Walsh C.T., Pai E.F.;
"Glutathione reductase turned into trypanothione reductase: structural analysis of an engineered change in substrate specificity.";
Biochemistry 36:6437-6447(1997).
[13]
X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 62-522.
DOI=10.1038/nsb0498-267; PubMed=9546215 [NCBI, ExPASy, EBI, Israel, Japan]
Becker K., Savvides S.N., Keese M., Schirmer R.H., Karplus P.A.;
"Enzyme inactivation through sulfhydryl oxidation by physiologic NO-carriers.";
Nat. Struct. Biol. 5:267-271(1998).
Comments
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
X15722; CAA33744.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF228703; AAF37572.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF228703; AAF37573.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF228704; AAF37574.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY338490; AAP88037.1; ALT_INIT; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF215848; -; NOT_ANNOTATED_CDS; Genomic_DNA.[EMBL / GenBank / DDBJ]
BC069244; AAH69244.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR S08979; RDHUU.
RefSeq NP_000628.2; -.
UniGene Hs.271510
3D structure databases
PDB
1ALG; NMR; -; A=480-503.[ExPASy / RCSB / EBI]
1BWC; X-ray; 2.10 A; A=45-522.[ExPASy / RCSB / EBI]
1DNC; X-ray; 1.70 A; A=45-522.[ExPASy / RCSB / EBI]
1GRA; X-ray; 2.00 A; A=45-522.[ExPASy / RCSB / EBI]
1GRB; X-ray; 1.85 A; A=45-522.[ExPASy / RCSB / EBI]
1GRE; X-ray; 2.00 A; A=45-522.[ExPASy / RCSB / EBI]
1GRF; X-ray; 2.00 A; A=45-522.[ExPASy / RCSB / EBI]
1GRG; X-ray; 2.00 A; A=45-522.[ExPASy / RCSB / EBI]
1GRH; X-ray; 3.00 A; A=45-522.[ExPASy / RCSB / EBI]
1GRT; X-ray; 2.30 A; A=45-522.[ExPASy / RCSB / EBI]
1GSN; X-ray; 1.70 A; A=45-522.[ExPASy / RCSB / EBI]
1K4Q; X-ray; 1.90 A; A=62-522.[ExPASy / RCSB / EBI]
1XAN; X-ray; 2.00 A; A=62-522.[ExPASy / RCSB / EBI]
2AAQ; X-ray; 2.60 A; A=44-522.[ExPASy / RCSB / EBI]
2GH5; X-ray; 1.70 A; A/B=45-522.[ExPASy / RCSB / EBI]
2GRT; X-ray; 2.70 A; A=62-522.[ExPASy / RCSB / EBI]
3GRS; X-ray; 1.54 A; A=45-522.[ExPASy / RCSB / EBI]
3GRT; X-ray; 2.50 A; A=62-522.[ExPASy / RCSB / EBI]
4GR1; X-ray; 2.40 A; A=45-522.[ExPASy / RCSB / EBI]
4GRT; X-ray; 2.80 A; A=62-522.[ExPASy / RCSB / EBI]
5GRT; X-ray; 2.40 A; A=62-522.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1ALG; -.
1BWC; -.
1DNC; -.
1GRA; -.
1GRB; -.
1GRE; -.
1GRF; -.
1GRG; -.
1GRH; -.
1GRT; -.
1GSN; -.
1K4Q; -.
1XAN; -.
2AAQ; -.
2GH5; -.
2GRT; -.
3GRS; -.
3GRT; -.
4GR1; -.
4GRT; -.
5GRT; -.
ModBase P00390.
PTM databases
PhosphoSite P00390; -.
Enzyme and pathway databases
BioCyc MetaCyc:MON-9902; -.
Reactome REACT_1698; Nucleotide metabolism.
Polymorphism databases
NIEHS-SNPs GSR.
2D gel databases
REPRODUCTION-2DPAGE IPI00759575; -.
Organism-specific databases
H-InvDB HIX0034273; -.
HGNC HGNC:4623; GSR.
GenAtlas GSR.
HPA CAB008632; -.
HPA001538; -.
MIM 138300; gene+phenotype. [NCBI / EBI]
Orphanet 90030; Haemolytic anaemia due to glutathione reductase deficiency.
PharmGKB PA29014; -.
GeneCards P00390.
Gene expression databases
ArrayExpress P00390; -.
CleanEx HS_GSR; -.
GermOnline ENSG00000104687; Homo sapiens.
Ontologies
GO
GO:0005829; Cellular component: cytosol (inferred from experiment from Reactome).
GO:0009055; Molecular function: electron carrier activity (traceable author statement from UniProtKB).
GO:0004362; Molecular function: glutathione-disulfide reductase activity (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR013027; FAD_pyr_nucl-diS_OxRdtase.
IPR006322; Glut_reduct_1.
IPR000815; Hg_reductase.
IPR001100; Pyr_nuc-diS_OxRdtase.
IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
IPR012999; Pyr_OxRdtase_I_AS.
IPR001327; Pyr_OxRdtase_NAD_bd.
Graphical view of domain structure.
Gene3D G3DSA:3.30.390.30; Pyr_redox_dim; 1.
Pfam PF00070; Pyr_redox; 1.
PF07992; Pyr_redox_2; 1.
PF02852; Pyr_redox_dim; 1.
Pfam graphical view of domain structure.
PRINTS PR00368; FADPNR.
PR00945; HGRDTASE.
PR00411; PNDRDTASEI.
ProDom PD000139; FAD_pyr_redox; 1.
[Domain structure / List of seq. sharing at least 1 domain]
TIGRFAMs TIGR01421; gluta_reduc_1; 1.
PROSITE PS00076; PYRIDINE_REDOX_1; 1.
BLOCKS P00390.
Genome annotation databases
Ensembl ENSG00000104687; Homo sapiens. [Contig view]
GeneID 2936; -.
KEGG hsa:2936; -.
NMPDR fig|9606.3.peg.30146; -.
Phylogenomic databases
HOGENOM P00390; -.
HOVERGEN P00390; -.
Other
DrugBank DB00262; Carmustine.
DB00143; Glutathione.
DB00157; NADH.
LinkHub P00390; -.
SOURCE GSR; Homo sapiens.
ProtoNet P00390.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Acetylation; Alternative initiation; Cytoplasm; Direct protein sequencing; FAD; Flavoprotein; Mitochondrion; NADP; Oxidoreductase; Phosphoprotein; Polymorphism; Redox-active center; Transit peptide.
Features
SEVIEWER logo Feature table viewer
KeyFrom   To Length Description FTId
TRANSIT   1    43  43     Mitochondrion (Potential). 
CHAIN   44   522  479     Glutathione reductase, mitochondrial. PRO_0000030276
NP_BIND   94   102  9     FAD. 
ACT_SITE   511   511        Proton acceptor. 
MOD_RES   65    65        Phosphotyrosine. 
DISULFID   102   107        Redox-active. 
DISULFID   134   134        Interchain. 
VAR_SEQ   1    43        Missing (in isoform Cytoplasmic). VSP_018972
VARIANT   153   153  1     R -> C. VAR_019079 [3D]
VARIANT   232   232  1     G -> S. VAR_019080 [3D]
VARIANT   261   261  1     I -> V. VAR_019081 [3D]
VARIANT   297   297  1     E -> D. VAR_019082 [3D]
VARIANT   314   314  1     P -> H (in dbSNP:rs2020916 [NCBI]). VAR_014554 [3D]
STRAND   66    70  5      
HELIX   74    85  12      
STRAND   90    96  7      
HELIX   100   104  5      
HELIX   107   125  19      
HELIX   127   129  3      
HELIX   140   164  25      
STRAND   168   172  5      
STRAND   183   186  4      
STRAND   189   192  4      
STRAND   196   198  3      
STRAND   202   204  3      
TURN   209   211  3      
HELIX   215   217  3      
HELIX   221   224  4      
STRAND   232   237  6      
HELIX   241   253  13      
STRAND   256   260  5      
STRAND   262   266  5      
HELIX   272   284  13      
STRAND   288   290  3      
STRAND   293   301  9      
STRAND   304   311  8      
STRAND   319   331  13      
STRAND   335   338  4      
HELIX   344   346  3      
STRAND   370   372  3      
HELIX   374   377  4      
HELIX   383   398  16      
STRAND   413   415  3      
STRAND   421   425  5      
HELIX   428   435  8      
HELIX   437   439  3      
STRAND   440   447  8      
HELIX   450   454  5      
STRAND   461   468  8      
TURN   469   472  4      
STRAND   473   481  9      
HELIX   484   496  13      
HELIX   501   505  5      
HELIX   515   519  5      
Sequence information
Length: 522 AA [This is the length of the unprocessed precursor] Molecular weight: 56257 Da [This is the MW of the unprocessed precursor] CRC64: DD8E2BA9D6E3757B [This is a checksum on the sequence]
        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 

P00390 in FASTA format

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