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Identification
HMDB Protein ID HMDBP00196
Secondary Accession Numbers
  • 5428
  • HMDBP04844
Name Glutathione reductase, mitochondrial
Synonyms
  1. GR
  2. GRase
Gene Name GSR
Protein Type Unknown
Biological Properties
General Function Involved in oxidoreductase activity
Specific Function Maintains high levels of reduced glutathione in the cytosol.
Pathways
  • 2-Hydroxyglutric Aciduria (D And L Form)
  • 4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency
  • 5-oxoprolinase deficiency
  • 5-Oxoprolinuria
  • Gamma-glutamyl-transpeptidase deficiency
  • Gamma-Glutamyltransferase Deficiency
  • Glutamate Metabolism
  • Glutathione Metabolism
  • Glutathione metabolism
  • Glutathione Synthetase Deficiency
  • Homocarnosinosis
  • Hyperinsulinism-Hyperammonemia Syndrome
  • Succinic semialdehyde dehydrogenase deficiency
Reactions
Glutathione + NADP → Oxidized glutathione + NADPH details
Glutathione + NAD → Oxidized glutathione + NADH + Hydrogen Ion details
Glutathione + NADP → Oxidized glutathione + NADPH + Hydrogen Ion details
GO Classification
Biological Process
cell redox homeostasis
spermatogenesis
nucleobase-containing small molecule interconversion
glutathione metabolic process
Cellular Component
cytosol
mitochondrion
Component
cell part
intracellular part
cytoplasm
Function
binding
nucleotide binding
catalytic activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
nadp or nadph binding
oxidoreductase activity, acting on a sulfur group of donors
disulfide oxidoreductase activity
peptide disulfide oxidoreductase activity
glutathione disulfide oxidoreductase activity
glutathione-disulfide reductase activity
oxidoreductase activity
fad or fadh2 binding
Molecular Function
electron carrier activity
glutathione binding
glutathione-disulfide reductase activity
NADP binding
flavin adenine dinucleotide binding
Process
metabolic process
cellular process
cellular metabolic process
peptide metabolic process
glutathione metabolic process
oxidation reduction
cellular homeostasis
cell redox homeostasis
Cellular Location
  1. Isoform Cytoplasmic:Cytoplasm
Gene Properties
Chromosome Location 8
Locus 8p21.1
SNPs GSR
Gene Sequence
>1569 bp
ATGGCCCTGCTGCCCCGAGCCCTGAGCGCCGGCGCGGGACCGAGCTGGCGGCGGGCGGCG
CGCGCCTTCCGAGGCTTCCTGCTGCTTCTGCCCGAGCCCGCGGCCCTCACGCGCGCCCTC
TCCCGTGCCATGGCCTGCAGGCAGGAGCCGCAGCCGCAGGGCCCGCCGCCCGCTGCTGGC
GCCGTGGCCTCCTATGACTACCTGGTGATCGGGGGCGGCTCGGGCGGGCTGGCCAGCGCG
CGCAGGGCGGCCGAGCTGGGTGCCAGGGCCGCCGTGGTGGAGAGCCACAAGCTGGGTGGC
ACTTGCGTGAATGTTGGATGTGTACCCAAAAAGGTAATGTGGAACACAGCTGTCCACTCT
GAATTCATGCATGATCATGCTGATTATGGCTTTCCAAGTTGTGAGGGTAAATTCAATTGG
CGTGTTATTAAGGAAAAGCGGGATGCCTATGTGAGCCGCCTGAATGCCATCTATCAAAAC
AATCTCACCAAGTCCCATATAGAAATCATCCGTGGCCATGCAGCCTTCACGAGTGATCCC
AAGCCCACAATAGAGGTCAGTGGGAAAAAGTACACCGCCCCACACATCCTGATCGCCACA
GGTGGTATGCCCTCCACCCCTCATGAGAGCCAGATCCCCGGTGCCAGCTTAGGAATAACC
AGCGATGGATTTTTTCAGCTGGAAGAATTGCCCGGCCGCAGCGTCATTGTTGGTGCAGGT
TACATTGCTGTGGAGATGGCAGGGATCCTGTCAGCCCTGGGTTCTAAGACATCACTGATG
ATACGGCATGATAAGGTACTTAGAAGTTTTGATTCAATGATCAGCACCAACTGCACGGAG
GAGCTGGAGAACGCTGGCGTGGAGGTGCTGAAGTTCTCCCAGGTCAAGGAGGTTAAAAAG
ACTTTGTCGGGCTTGGAAGTCAGCATGGTTACTGCAGTTCCCGGTAGGCTACCAGTCATG
ACCATGATTCCAGATGTTGACTGCCTGCTCTGGGCCATTGGGCGGGTCCCGAATACCAAG
GACCTGAGTTTAAACAAACTGGGGATTCAAACCGATGACAAGGGTCATATCATCGTAGAC
GAATTCCAGAATACCAACGTCAAAGGCATCTATGCAGTTGGGGATGTATGTGGAAAAGCT
CTTCTTACTCCAGTTGCAATAGCTGCTGGCCGAAAACTTGCCCATCGACTTTTTGAATAT
AAGGAAGATTCCAAATTAGATTATAACAACATCCCAACTGTGGTCTTCAGCCACCCCCCT
ATTGGGACAGTGGGACTCACGGAAGATGAAGCCATTCATAAATATGGAATAGAAAATGTG
AAGACCTATTCAACGAGCTTTACCCCGATGTATCACGCAGTTACCAAAAGGAAAACAAAA
TGTGTGATGAAAATGGTCTGTGCTAACAAGGAAGAAAAGGTGGTTGGGATCCATATGCAG
GGACTTGGGTGTGATGAAATGCTGCAGGGTTTTGCTGTTGCAGTGAAGATGGGAGCAACG
AAGGCAGACTTTGACAACACAGTCGCCATTCACCCTACCTCTTCAGAAGAGCTGGTCACA
CTTCGTTGA
Protein Properties
Number of Residues 522
Molecular Weight 56256.565
Theoretical pI 8.495
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Glutathione reductase, mitochondrial
MALLPRALSAGAGPSWRRAARAFRGFLLLLPEPAALTRALSRAMACRQEPQPQGPPPAAG
AVASYDYLVIGGGSGGLASARRAAELGARAAVVESHKLGGTCVNVGCVPKKVMWNTAVHS
EFMHDHADYGFPSCEGKFNWRVIKEKRDAYVSRLNAIYQNNLTKSHIEIIRGHAAFTSDP
KPTIEVSGKKYTAPHILIATGGMPSTPHESQIPGASLGITSDGFFQLEELPGRSVIVGAG
YIAVEMAGILSALGSKTSLMIRHDKVLRSFDSMISTNCTEELENAGVEVLKFSQVKEVKK
TLSGLEVSMVTAVPGRLPVMTMIPDVDCLLWAIGRVPNTKDLSLNKLGIQTDDKGHIIVD
EFQNTNVKGIYAVGDVCGKALLTPVAIAAGRKLAHRLFEYKEDSKLDYNNIPTVVFSHPP
IGTVGLTEDEAIHKYGIENVKTYSTSFTPMYHAVTKRKTKCVMKMVCANKEEKVVGIHMQ
GLGCDEMLQGFAVAVKMGATKADFDNTVAIHPTSSEELVTLR
GenBank ID Protein 50301238
UniProtKB/Swiss-Prot ID P00390
UniProtKB/Swiss-Prot Entry Name GSHR_HUMAN
PDB IDs
GenBank Gene ID NM_000637.3
GeneCard ID GSR
GenAtlas ID GSR
HGNC ID HGNC:4623
References
General References
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  2. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ: Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol. 2005 Jan;23(1):94-101. Epub 2004 Dec 12. [PubMed:15592455 ]
  3. Nusbaum C, Mikkelsen TS, Zody MC, Asakawa S, Taudien S, Garber M, Kodira CD, Schueler MG, Shimizu A, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Allen NR, Anderson S, Asakawa T, Blechschmidt K, Bloom T, Borowsky ML, Butler J, Cook A, Corum B, DeArellano K, DeCaprio D, Dooley KT, Dorris L 3rd, Engels R, Glockner G, Hafez N, Hagopian DS, Hall JL, Ishikawa SK, Jaffe DB, Kamat A, Kudoh J, Lehmann R, Lokitsang T, Macdonald P, Major JE, Matthews CD, Mauceli E, Menzel U, Mihalev AH, Minoshima S, Murayama Y, Naylor JW, Nicol R, Nguyen C, O'Leary SB, O'Neill K, Parker SC, Polley A, Raymond CK, Reichwald K, Rodriguez J, Sasaki T, Schilhabel M, Siddiqui R, Smith CL, Sneddon TP, Talamas JA, Tenzin P, Topham K, Venkataraman V, Wen G, Yamazaki S, Young SK, Zeng Q, Zimmer AR, Rosenthal A, Birren BW, Platzer M, Shimizu N, Lander ES: DNA sequence and analysis of human chromosome 8. Nature. 2006 Jan 19;439(7074):331-5. [PubMed:16421571 ]
  4. Tutic M, Lu XA, Schirmer RH, Werner D: Cloning and sequencing of mammalian glutathione reductase cDNA. Eur J Biochem. 1990 Mar 30;188(3):523-8. [PubMed:2185014 ]
  5. Kelner MJ, Montoya MA: Structural organization of the human glutathione reductase gene: determination of correct cDNA sequence and identification of a mitochondrial leader sequence. Biochem Biophys Res Commun. 2000 Mar 16;269(2):366-8. [PubMed:10708558 ]
  6. Krauth-Siegel RL, Blatterspiel R, Saleh M, Schiltz E, Schirmer RH, Untucht-Grau R: Glutathione reductase from human erythrocytes. The sequences of the NADPH domain and of the interface domain. Eur J Biochem. 1982 Jan;121(2):259-67. [PubMed:7060551 ]
  7. Krohne-Ehrich G, Schirmer RH, Untucht-Grau R: Glutathione reductase from human erythrocytes. Isolation of the enzyme and sequence analysis of the redox-active peptide. Eur J Biochem. 1977 Oct 17;80(1):65-71. [PubMed:923580 ]
  8. Thieme R, Pai EF, Schirmer RH, Schulz GE: Three-dimensional structure of glutathione reductase at 2 A resolution. J Mol Biol. 1981 Nov 15;152(4):763-82. [PubMed:7334521 ]
  9. Karplus PA, Schulz GE: Refined structure of glutathione reductase at 1.54 A resolution. J Mol Biol. 1987 Jun 5;195(3):701-29. [PubMed:3656429 ]
  10. Savvides SN, Karplus PA: Kinetics and crystallographic analysis of human glutathione reductase in complex with a xanthene inhibitor. J Biol Chem. 1996 Apr 5;271(14):8101-7. [PubMed:8626496 ]
  11. Stoll VS, Simpson SJ, Krauth-Siegel RL, Walsh CT, Pai EF: Glutathione reductase turned into trypanothione reductase: structural analysis of an engineered change in substrate specificity. Biochemistry. 1997 May 27;36(21):6437-47. [PubMed:9174360 ]
  12. Becker K, Savvides SN, Keese M, Schirmer RH, Karplus PA: Enzyme inactivation through sulfhydryl oxidation by physiologic NO-carriers. Nat Struct Biol. 1998 Apr;5(4):267-71. [PubMed:9546215 ]