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Protein

Glutathione reductase, mitochondrial

Gene

GSR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Maintains high levels of reduced glutathione in the cytosol.

Miscellaneous

The active site is a redox-active disulfide bond.

Catalytic activityi

2 glutathione + NADP+ = glutathione disulfide + NADPH.

Cofactori

FADNote: Binds 1 FAD per subunit.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei511Proton acceptor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi94 – 102FAD9

GO - Molecular functioni

  • electron transfer activity Source: UniProtKB
  • flavin adenine dinucleotide binding Source: GO_Central
  • glutathione-disulfide reductase activity Source: GO_Central
  • NADP binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
LigandFAD, Flavoprotein, NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS02602-MONOMER
BRENDAi1.8.1.7 2681
ReactomeiR-HSA-2408550 Metabolism of ingested H2SeO4 and H2SeO3 into H2Se
R-HSA-3299685 Detoxification of Reactive Oxygen Species
R-HSA-499943 Interconversion of nucleotide di- and triphosphates
R-HSA-5628897 TP53 Regulates Metabolic Genes
SABIO-RKiP00390

Names & Taxonomyi

Protein namesi
Recommended name:
Glutathione reductase, mitochondrial (EC:1.8.1.7)
Short name:
GR
Short name:
GRase
Gene namesi
Name:GSR
Synonyms:GLUR, GRD1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000104687.12
HGNCiHGNC:4623 GSR
MIMi138300 gene+phenotype
neXtProtiNX_P00390

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Organism-specific databases

DisGeNETi2936
MalaCardsiGSR
MIMi138300 gene+phenotype
OpenTargetsiENSG00000104687
Orphaneti90030 Hemolytic anemia due to glutathione reductase deficiency
PharmGKBiPA29014

Chemistry databases

ChEMBLiCHEMBL2755
DrugBankiDB02895 3-(Prop-2-Ene-1-Sulfinyl)-Propene-1-Thiol
DB02153 3-Sulfinoalanine
DB00262 Carmustine
DB03147 Flavin adenine dinucleotide
DB00143 Glutathione
DB02553 Glutathionylspermidine Disulfide
DB09110 Mesna
DB03867 Meta-Nitro-Tyrosine
DB00157 NADH
DB03310 Oxidized Glutathione Disulfide

Polymorphism and mutation databases

BioMutaiGSR
DMDMi14916998

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 43MitochondrionSequence analysisAdd BLAST43
ChainiPRO_000003027644 – 522Glutathione reductase, mitochondrialAdd BLAST479

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei97N6-acetyllysineBy similarity1
Disulfide bondi102 ↔ 107Redox-active1 Publication
Disulfide bondi134Interchain1 Publication

Keywords - PTMi

Acetylation, Disulfide bond

Proteomic databases

EPDiP00390
PaxDbiP00390
PeptideAtlasiP00390
PRIDEiP00390
ProteomicsDBi51241
51242 [P00390-2]
51243 [P00390-3]
51244 [P00390-4]
51245 [P00390-5]

2D gel databases

REPRODUCTION-2DPAGEiIPI00759575

PTM databases

CarbonylDBiP00390
iPTMnetiP00390
PhosphoSitePlusiP00390

Expressioni

Gene expression databases

BgeeiENSG00000104687 Expressed in 218 organ(s), highest expression level in endometrium
CleanExiHS_GSR
ExpressionAtlasiP00390 baseline and differential
GenevisibleiP00390 HS

Organism-specific databases

HPAiCAB008632
HPA001538

Interactioni

Subunit structurei

Homodimer; disulfide-linked.1 Publication

Protein-protein interaction databases

BioGridi109191, 31 interactors
IntActiP00390, 6 interactors
MINTiP00390
STRINGi9606.ENSP00000221130

Chemistry databases

BindingDBiP00390

Structurei

Secondary structure

1522
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP00390
SMRiP00390
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP00390

Family & Domainsi

Domaini

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.

Sequence similaritiesi

Keywords - Domaini

Redox-active center, Transit peptide

Phylogenomic databases

eggNOGiKOG0405 Eukaryota
COG1249 LUCA
GeneTreeiENSGT00390000007578
HOGENOMiHOG000276712
HOVERGENiHBG004959
InParanoidiP00390
KOiK00383
OMAiKCAIIEA
OrthoDBiEOG091G078A
PhylomeDBiP00390
TreeFamiTF105353

Family and domain databases

Gene3Di3.30.390.30, 1 hit
3.50.50.60, 2 hits
InterProiView protein in InterPro
IPR036188 FAD/NAD-bd_sf
IPR023753 FAD/NAD-binding_dom
IPR016156 FAD/NAD-linked_Rdtase_dimer_sf
IPR006322 Glutathione_Rdtase_euk/bac
IPR001100 Pyr_nuc-diS_OxRdtase
IPR004099 Pyr_nucl-diS_OxRdtase_dimer
IPR012999 Pyr_OxRdtase_I_AS
PANTHERiPTHR42737 PTHR42737, 1 hit
PfamiView protein in Pfam
PF07992 Pyr_redox_2, 1 hit
PF02852 Pyr_redox_dim, 1 hit
PIRSFiPIRSF000350 Mercury_reductase_MerA, 1 hit
SUPFAMiSSF51905 SSF51905, 1 hit
SSF55424 SSF55424, 1 hit
TIGRFAMsiTIGR01421 gluta_reduc_1, 1 hit
PROSITEiView protein in PROSITE
PS00076 PYRIDINE_REDOX_1, 1 hit

Sequences (5+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

This entry has 5 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform Mitochondrial (identifier: P00390-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MALLPRALSA GAGPSWRRAA RAFRGFLLLL PEPAALTRAL SRAMACRQEP
60 70 80 90 100
QPQGPPPAAG AVASYDYLVI GGGSGGLASA RRAAELGARA AVVESHKLGG
110 120 130 140 150
TCVNVGCVPK KVMWNTAVHS EFMHDHADYG FPSCEGKFNW RVIKEKRDAY
160 170 180 190 200
VSRLNAIYQN NLTKSHIEII RGHAAFTSDP KPTIEVSGKK YTAPHILIAT
210 220 230 240 250
GGMPSTPHES QIPGASLGIT SDGFFQLEEL PGRSVIVGAG YIAVEMAGIL
260 270 280 290 300
SALGSKTSLM IRHDKVLRSF DSMISTNCTE ELENAGVEVL KFSQVKEVKK
310 320 330 340 350
TLSGLEVSMV TAVPGRLPVM TMIPDVDCLL WAIGRVPNTK DLSLNKLGIQ
360 370 380 390 400
TDDKGHIIVD EFQNTNVKGI YAVGDVCGKA LLTPVAIAAG RKLAHRLFEY
410 420 430 440 450
KEDSKLDYNN IPTVVFSHPP IGTVGLTEDE AIHKYGIENV KTYSTSFTPM
460 470 480 490 500
YHAVTKRKTK CVMKMVCANK EEKVVGIHMQ GLGCDEMLQG FAVAVKMGAT
510 520
KADFDNTVAI HPTSSEELVT LR
Length:522
Mass (Da):56,257
Last modified:July 11, 2001 - v2
Checksum:iDD8E2BA9D6E3757B
GO
Isoform Cytoplasmic (identifier: P00390-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-43: Missing.

Note: Produced by alternative initiation of isoform Mitochondrial.
Show »
Length:479
Mass (Da):51,701
Checksum:i3C0A194C96E880E7
GO
Isoform 2 (identifier: P00390-3) [UniParc]FASTAAdd to basket
Also known as: delta8

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

Show »
Length:493
Mass (Da):53,027
Checksum:iEFBA71DCDCFF1529
GO
Isoform 3 (identifier: P00390-4) [UniParc]FASTAAdd to basket
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.
Show »
Length:469
Mass (Da):50,497
Checksum:i0AD475B02A87C63E
GO
Isoform 4 (identifier: P00390-5) [UniParc]FASTAAdd to basket
Also known as: delta8+9

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

Show »
Length:440
Mass (Da):47,267
Checksum:i793E0A9F8706B1B5
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YC68H0YC68_HUMAN
Glutathione reductase, mitochondria...
GSR
131Annotation score:
A0A2R8YF59A0A2R8YF59_HUMAN
Glutathione reductase, mitochondria...
GSR
123Annotation score:

Sequence cautioni

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019079153R → C1 PublicationCorresponds to variant dbSNP:rs8190955Ensembl.1
Natural variantiVAR_051775232G → R. Corresponds to variant dbSNP:rs8190976Ensembl.1
Natural variantiVAR_019080232G → S1 PublicationCorresponds to variant dbSNP:rs8190976Ensembl.1
Natural variantiVAR_019081261I → V1 PublicationCorresponds to variant dbSNP:rs8190997Ensembl.1
Natural variantiVAR_019082297E → D1 PublicationCorresponds to variant dbSNP:rs8191004Ensembl.1
Natural variantiVAR_014554314P → H. Corresponds to variant dbSNP:rs2020916Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0189721 – 43Missing in isoform Cytoplasmic. 1 PublicationAdd BLAST43
Alternative sequenceiVSP_042908266 – 294Missing in isoform 2 and isoform 4. 1 PublicationAdd BLAST29
Alternative sequenceiVSP_042909295 – 347Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST53

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS34877.1 [P00390-1]
CCDS56530.1 [P00390-5]
CCDS56531.1 [P00390-3]
CCDS56532.1 [P00390-4]
PIRiS08979 RDHUU
RefSeqiNP_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]
UniGeneiHs.271510

Genome annotation databases

EnsembliENST00000221130; ENSP00000221130; ENSG00000104687 [P00390-1]
ENST00000537535; ENSP00000438845; ENSG00000104687 [P00390-5]
ENST00000541648; ENSP00000444559; ENSG00000104687 [P00390-4]
ENST00000546342; ENSP00000445516; ENSG00000104687 [P00390-3]
GeneIDi2936
KEGGihsa:2936
UCSCiuc022ato.2 human [P00390-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

Glutathione reductase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS34877.1 [P00390-1]
CCDS56530.1 [P00390-5]
CCDS56531.1 [P00390-3]
CCDS56532.1 [P00390-4]
PIRiS08979 RDHUU
RefSeqiNP_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]
UniGeneiHs.271510

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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-ray1.80X45-522[»]
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[»]
ProteinModelPortaliP00390
SMRiP00390
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109191, 31 interactors
IntActiP00390, 6 interactors
MINTiP00390
STRINGi9606.ENSP00000221130

Chemistry databases

BindingDBiP00390
ChEMBLiCHEMBL2755
DrugBankiDB02895 3-(Prop-2-Ene-1-Sulfinyl)-Propene-1-Thiol
DB02153 3-Sulfinoalanine
DB00262 Carmustine
DB03147 Flavin adenine dinucleotide
DB00143 Glutathione
DB02553 Glutathionylspermidine Disulfide
DB09110 Mesna
DB03867 Meta-Nitro-Tyrosine
DB00157 NADH
DB03310 Oxidized Glutathione Disulfide

PTM databases

CarbonylDBiP00390
iPTMnetiP00390
PhosphoSitePlusiP00390

Polymorphism and mutation databases

BioMutaiGSR
DMDMi14916998

2D gel databases

REPRODUCTION-2DPAGEiIPI00759575

Proteomic databases

EPDiP00390
PaxDbiP00390
PeptideAtlasiP00390
PRIDEiP00390
ProteomicsDBi51241
51242 [P00390-2]
51243 [P00390-3]
51244 [P00390-4]
51245 [P00390-5]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000221130; ENSP00000221130; ENSG00000104687 [P00390-1]
ENST00000537535; ENSP00000438845; ENSG00000104687 [P00390-5]
ENST00000541648; ENSP00000444559; ENSG00000104687 [P00390-4]
ENST00000546342; ENSP00000445516; ENSG00000104687 [P00390-3]
GeneIDi2936
KEGGihsa:2936
UCSCiuc022ato.2 human [P00390-1]

Organism-specific databases

CTDi2936
DisGeNETi2936
EuPathDBiHostDB:ENSG00000104687.12
GeneCardsiGSR
HGNCiHGNC:4623 GSR
HPAiCAB008632
HPA001538
MalaCardsiGSR
MIMi138300 gene+phenotype
neXtProtiNX_P00390
OpenTargetsiENSG00000104687
Orphaneti90030 Hemolytic anemia due to glutathione reductase deficiency
PharmGKBiPA29014
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0405 Eukaryota
COG1249 LUCA
GeneTreeiENSGT00390000007578
HOGENOMiHOG000276712
HOVERGENiHBG004959
InParanoidiP00390
KOiK00383
OMAiKCAIIEA
OrthoDBiEOG091G078A
PhylomeDBiP00390
TreeFamiTF105353

Enzyme and pathway databases

BioCyciMetaCyc:HS02602-MONOMER
BRENDAi1.8.1.7 2681
ReactomeiR-HSA-2408550 Metabolism of ingested H2SeO4 and H2SeO3 into H2Se
R-HSA-3299685 Detoxification of Reactive Oxygen Species
R-HSA-499943 Interconversion of nucleotide di- and triphosphates
R-HSA-5628897 TP53 Regulates Metabolic Genes
SABIO-RKiP00390

Miscellaneous databases

EvolutionaryTraceiP00390
GeneWikiiGlutathione_reductase
GenomeRNAii2936
PROiPR:P00390
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000104687 Expressed in 218 organ(s), highest expression level in endometrium
CleanExiHS_GSR
ExpressionAtlasiP00390 baseline and differential
GenevisibleiP00390 HS

Family and domain databases

Gene3Di3.30.390.30, 1 hit
3.50.50.60, 2 hits
InterProiView protein in InterPro
IPR036188 FAD/NAD-bd_sf
IPR023753 FAD/NAD-binding_dom
IPR016156 FAD/NAD-linked_Rdtase_dimer_sf
IPR006322 Glutathione_Rdtase_euk/bac
IPR001100 Pyr_nuc-diS_OxRdtase
IPR004099 Pyr_nucl-diS_OxRdtase_dimer
IPR012999 Pyr_OxRdtase_I_AS
PANTHERiPTHR42737 PTHR42737, 1 hit
PfamiView protein in Pfam
PF07992 Pyr_redox_2, 1 hit
PF02852 Pyr_redox_dim, 1 hit
PIRSFiPIRSF000350 Mercury_reductase_MerA, 1 hit
SUPFAMiSSF51905 SSF51905, 1 hit
SSF55424 SSF55424, 1 hit
TIGRFAMsiTIGR01421 gluta_reduc_1, 1 hit
PROSITEiView protein in PROSITE
PS00076 PYRIDINE_REDOX_1, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGSHR_HUMAN
AccessioniPrimary (citable) accession number: P00390
Secondary accession number(s): C8KIL8
, C8KIL9, C8KIM0, D3DSV3, Q7Z5C9, Q9NP63
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 11, 2001
Last modified: November 7, 2018
This is version 232 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
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