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Protein

Glutaredoxin-2, mitochondrial

Gene

Glrx2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Glutathione-dependent oxidoreductase that facilitates the maintenance of mitochondrial redox homeostasis upon induction of apoptosis by oxidative stress. Involved in response to hydrogen peroxide and regulation of apoptosis caused by oxidative stress. Acts as a very efficient catalyst of monothiol reactions because of its high affinity for protein glutathione-mixed disulfides. Can receive electrons not only from glutathione (GSH), but also from thioredoxin reductase supporting both monothiol and dithiol reactions. Efficiently catalyzes both glutathionylation and deglutathionylation of mitochondrial complex I, which in turn regulates the superoxide production by the complex. Overexpression decreases the susceptibility to apoptosis and prevents loss of cardiolipin and cytochrome c release.2 Publications

Enzyme regulationi

The 2Fe-2S present in the homodimer leads to inactivation of the enzyme. The 2Fe-2S may serve as a redox sensor: the presence of one-electron oxidants or reductants leading to the loss of the 2Fe-2S cluster, subsequent monomerization and activation of the enzyme (By similarity).By similarity

Kineticsi

  1. KM=1.68 mM for HEDS1 Publication
  2. KM=1.77 mM for S-sulfocysteine1 Publication
  3. KM=0.3 mM for L-cystine1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi61 – 611Iron-sulfur (2Fe-2S); shared with dimeric partner; in inactive formBy similarity
    Binding sitei67 – 671GlutathioneBy similarity
    Binding sitei102 – 1021GlutathioneBy similarity
    Binding sitei114 – 1141Glutathione; via amide nitrogen and carbonyl oxygenBy similarity
    Metal bindingi146 – 1461Iron-sulfur (2Fe-2S); shared with dimeric partner; in inactive formBy similarity

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Biological processi

    Electron transport, Transport

    Keywords - Ligandi

    2Fe-2S, Iron, Iron-sulfur, Metal-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Glutaredoxin-2, mitochondrial
    Gene namesi
    Name:Glrx2
    Synonyms:Grx2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589 Componenti: Chromosome 1

    Organism-specific databases

    MGIiMGI:1916617. Glrx2.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Mitochondrion, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 1919MitochondrionSequence AnalysisAdd
    BLAST
    Chaini20 – 156137Glutaredoxin-2, mitochondrialPRO_0000011629Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi70 ↔ 73Redox-active; alternateBy similarity
    Modified residuei70 – 701S-glutathionyl cysteine; alternateBy similarity

    Keywords - PTMi

    Disulfide bond, Glutathionylation

    Proteomic databases

    MaxQBiQ923X4.
    PaxDbiQ923X4.
    PRIDEiQ923X4.

    PTM databases

    PhosphoSiteiQ923X4.

    Expressioni

    Tissue specificityi

    Widely expressed. Highly expressed in testis, and at much lower level in kidney and brain.1 Publication

    Developmental stagei

    During development, it is expressed at highest level at E11.1 Publication

    Gene expression databases

    BgeeiQ923X4.
    CleanExiMM_GLRX2.
    ExpressionAtlasiQ923X4. baseline and differential.
    GenevisibleiQ923X4. MM.

    Interactioni

    Subunit structurei

    Monomer; active form. Homodimer; inactive form. The homodimer is probably linked by 1 2Fe-2S cluster (By similarity).By similarity

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000053443.

    Structurei

    3D structure databases

    ProteinModelPortaliQ923X4.
    SMRiQ923X4. Positions 49-148.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini50 – 150101GlutaredoxinPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the glutaredoxin family.Curated
    Contains 1 glutaredoxin domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Redox-active center, Transit peptide

    Phylogenomic databases

    eggNOGiKOG1752.
    GeneTreeiENSGT00390000003677.
    HOGENOMiHOG000095204.
    HOVERGENiHBG096801.
    InParanoidiQ923X4.
    KOiK03676.
    OMAiNYTAVEL.
    OrthoDBiEOG7QRQWZ.
    PhylomeDBiQ923X4.
    TreeFamiTF319627.

    Family and domain databases

    Gene3Di3.40.30.10. 1 hit.
    InterProiIPR002109. Glutaredoxin.
    IPR011899. Glutaredoxin_euk/vir.
    IPR014025. Glutaredoxin_subgr.
    IPR012336. Thioredoxin-like_fold.
    [Graphical view]
    PfamiPF00462. Glutaredoxin. 1 hit.
    [Graphical view]
    PRINTSiPR00160. GLUTAREDOXIN.
    SUPFAMiSSF52833. SSF52833. 1 hit.
    TIGRFAMsiTIGR02180. GRX_euk. 1 hit.
    PROSITEiPS51354. GLUTAREDOXIN_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q923X4-1) [UniParc]FASTAAdd to basket

    Also known as: Grx2a

    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
    MSWRRAASVG RRLVASGRIL AGRRGAAGAA GSGMGNSTSS FWGKSTTTPV
    60 70 80 90 100
    NQIQETISNN CVVIFSKTSC SYCSMAKKIF HDMNVNYKAV ELDMLEYGNQ
    110 120 130 140 150
    FQDALHKMTG ERTVPRIFVN GRFIGGAADT HRLHKEGKLL PLVHQCYLKK

    KQEERH
    Length:156
    Mass (Da):17,307
    Last modified:December 1, 2001 - v1
    Checksum:i605BA5C62A139C3E
    GO
    Isoform 2 (identifier: Q923X4-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-33: Missing.

    Show »
    Length:123
    Mass (Da):14,042
    Checksum:i803375159539AECD
    GO

    Sequence cautioni

    The sequence AAF86465.1 differs from that shown. Reason: Frameshift at position 128. Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 3333Missing in isoform 2. 2 PublicationsVSP_015222Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF380337 mRNA. Translation: AAK85319.1.
    AF276918 mRNA. Translation: AAF86465.1. Frameshift.
    AK005853 mRNA. Translation: BAB24276.1.
    CCDSiCCDS15343.1. [Q923X4-1]
    CCDS15344.1. [Q923X4-2]
    RefSeqiNP_001033681.1. NM_001038592.1. [Q923X4-1]
    NP_001033682.1. NM_001038593.1. [Q923X4-2]
    NP_001033683.1. NM_001038594.1. [Q923X4-2]
    NP_075994.2. NM_023505.2. [Q923X4-2]
    XP_006529919.1. XM_006529856.2. [Q923X4-2]
    UniGeneiMm.272727.

    Genome annotation databases

    EnsembliENSMUST00000111957; ENSMUSP00000107588; ENSMUSG00000018196. [Q923X4-2]
    ENSMUST00000129653; ENSMUSP00000121010; ENSMUSG00000018196. [Q923X4-2]
    ENSMUST00000145969; ENSMUSP00000121665; ENSMUSG00000018196. [Q923X4-2]
    ENSMUST00000185362; ENSMUSP00000141022; ENSMUSG00000018196. [Q923X4-1]
    GeneIDi69367.
    KEGGimmu:69367.
    UCSCiuc007cwz.1. mouse. [Q923X4-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF380337 mRNA. Translation: AAK85319.1.
    AF276918 mRNA. Translation: AAF86465.1. Frameshift.
    AK005853 mRNA. Translation: BAB24276.1.
    CCDSiCCDS15343.1. [Q923X4-1]
    CCDS15344.1. [Q923X4-2]
    RefSeqiNP_001033681.1. NM_001038592.1. [Q923X4-1]
    NP_001033682.1. NM_001038593.1. [Q923X4-2]
    NP_001033683.1. NM_001038594.1. [Q923X4-2]
    NP_075994.2. NM_023505.2. [Q923X4-2]
    XP_006529919.1. XM_006529856.2. [Q923X4-2]
    UniGeneiMm.272727.

    3D structure databases

    ProteinModelPortaliQ923X4.
    SMRiQ923X4. Positions 49-148.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000053443.

    PTM databases

    PhosphoSiteiQ923X4.

    Proteomic databases

    MaxQBiQ923X4.
    PaxDbiQ923X4.
    PRIDEiQ923X4.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000111957; ENSMUSP00000107588; ENSMUSG00000018196. [Q923X4-2]
    ENSMUST00000129653; ENSMUSP00000121010; ENSMUSG00000018196. [Q923X4-2]
    ENSMUST00000145969; ENSMUSP00000121665; ENSMUSG00000018196. [Q923X4-2]
    ENSMUST00000185362; ENSMUSP00000141022; ENSMUSG00000018196. [Q923X4-1]
    GeneIDi69367.
    KEGGimmu:69367.
    UCSCiuc007cwz.1. mouse. [Q923X4-1]

    Organism-specific databases

    CTDi51022.
    MGIiMGI:1916617. Glrx2.

    Phylogenomic databases

    eggNOGiKOG1752.
    GeneTreeiENSGT00390000003677.
    HOGENOMiHOG000095204.
    HOVERGENiHBG096801.
    InParanoidiQ923X4.
    KOiK03676.
    OMAiNYTAVEL.
    OrthoDBiEOG7QRQWZ.
    PhylomeDBiQ923X4.
    TreeFamiTF319627.

    Miscellaneous databases

    NextBioi329240.
    PROiQ923X4.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ923X4.
    CleanExiMM_GLRX2.
    ExpressionAtlasiQ923X4. baseline and differential.
    GenevisibleiQ923X4. MM.

    Family and domain databases

    Gene3Di3.40.30.10. 1 hit.
    InterProiIPR002109. Glutaredoxin.
    IPR011899. Glutaredoxin_euk/vir.
    IPR014025. Glutaredoxin_subgr.
    IPR012336. Thioredoxin-like_fold.
    [Graphical view]
    PfamiPF00462. Glutaredoxin. 1 hit.
    [Graphical view]
    PRINTSiPR00160. GLUTAREDOXIN.
    SUPFAMiSSF52833. SSF52833. 1 hit.
    TIGRFAMsiTIGR02180. GRX_euk. 1 hit.
    PROSITEiPS51354. GLUTAREDOXIN_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Identification and characterization of a new mammalian glutaredoxin (thioltransferase), Grx2."
      Gladyshev V.N., Liu A., Novoselov S.V., Krysan K., Sun Q.-A., Kryukov V.M., Kryukov G.V., Lou M.F.
      J. Biol. Chem. 276:30374-30380(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION.
    2. Reddy P.G., Bhuyan D.K., Bhuyan K.C.
      Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
      Strain: CFW.
      Tissue: Lens.
    3. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Strain: C57BL/6J.
      Tissue: Testis.
    4. "Absolute gene expression patterns of thioredoxin and glutaredoxin redox systems in mouse."
      Jurado J., Prieto-Alamo M.-J., Madrid-Risquez J., Pueyo C.
      J. Biol. Chem. 278:45546-45554(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    5. "Glutaredoxin 2 catalyzes the reversible oxidation and glutathionylation of mitochondrial membrane thiol proteins: implications for mitochondrial redox regulation and antioxidant defense."
      Beer S.M., Taylor E.R., Brown S.E., Dahm C.C., Costa N.J., Runswick M.J., Murphy M.P.
      J. Biol. Chem. 279:47939-47951(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiGLRX2_MOUSE
    AccessioniPrimary (citable) accession number: Q923X4
    Secondary accession number(s): Q9DAG8, Q9JHY6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 30, 2005
    Last sequence update: December 1, 2001
    Last modified: June 24, 2015
    This is version 108 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.