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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

  1. 2 iron, 2 sulfur cluster binding Source: UniProtKB-KW
  2. electron carrier activity Source: InterPro
  3. metal ion binding Source: UniProtKB-KW
  4. protein disulfide oxidoreductase activity Source: InterPro

GO - Biological processi

  1. cell redox homeostasis Source: InterPro
  2. response to hydrogen peroxide Source: UniProtKB
  3. response to organic substance Source: UniProtKB
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: Chromosome 1

Organism-specific databases

MGIiMGI:1916617. Glrx2.

Subcellular locationi

GO - Cellular componenti

  1. intracellular membrane-bounded organelle Source: MGI
  2. mitochondrion Source: UniProtKB
  3. nucleoplasm Source: MGI
  4. nucleus Source: UniProtKB
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.
GenevestigatoriQ923X4.

Interactioni

Subunit structurei

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

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_006529856.1. [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_006529856.1. [Q923X4-2]
UniGeneiMm.272727.

3D structure databases

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

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.
GenevestigatoriQ923X4.

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: March 4, 2015
This is version 105 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.