ID   GLRX2_MOUSE             Reviewed;         156 AA.
AC   Q923X4; Q9DAG8; Q9JHY6;
DT   30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   24-JAN-2024, entry version 155.
DE   RecName: Full=Glutaredoxin-2, mitochondrial;
DE   Flags: Precursor;
GN   Name=Glrx2; Synonyms=Grx2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING (ISOFORMS 1
RP   AND 2), FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR LOCATION.
RX   PubMed=11397793; DOI=10.1074/jbc.m100020200;
RA   Gladyshev V.N., Liu A., Novoselov S.V., Krysan K., Sun Q.-A., Kryukov V.M.,
RA   Kryukov G.V., Lou M.F.;
RT   "Identification and characterization of a new mammalian glutaredoxin
RT   (thioltransferase), Grx2.";
RL   J. Biol. Chem. 276:30374-30380(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC   STRAIN=CFW; TISSUE=Lens;
RA   Reddy P.G., Bhuyan D.K., Bhuyan K.C.;
RL   Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   STRAIN=C57BL/6J; TISSUE=Testis;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=12954614; DOI=10.1074/jbc.m307866200;
RA   Jurado J., Prieto-Alamo M.-J., Madrid-Risquez J., Pueyo C.;
RT   "Absolute gene expression patterns of thioredoxin and glutaredoxin redox
RT   systems in mouse.";
RL   J. Biol. Chem. 278:45546-45554(2003).
RN   [5]
RP   FUNCTION.
RX   PubMed=15347644; DOI=10.1074/jbc.m408011200;
RA   Beer S.M., Taylor E.R., Brown S.E., Dahm C.C., Costa N.J., Runswick M.J.,
RA   Murphy M.P.;
RT   "Glutaredoxin 2 catalyzes the reversible oxidation and glutathionylation of
RT   mitochondrial membrane thiol proteins: implications for mitochondrial redox
RT   regulation and antioxidant defense.";
RL   J. Biol. Chem. 279:47939-47951(2004).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, and Kidney;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Glutathione-dependent oxidoreductase that facilitates the
CC       maintenance of mitochondrial redox homeostasis upon induction of
CC       apoptosis by oxidative stress. Involved in response to hydrogen
CC       peroxide and regulation of apoptosis caused by oxidative stress. Acts
CC       as a very efficient catalyst of monothiol reactions because of its high
CC       affinity for protein glutathione-mixed disulfides. Can receive
CC       electrons not only from glutathione (GSH), but also from thioredoxin
CC       reductase supporting both monothiol and dithiol reactions. Efficiently
CC       catalyzes both glutathionylation and deglutathionylation of
CC       mitochondrial complex I, which in turn regulates the superoxide
CC       production by the complex. Overexpression decreases the susceptibility
CC       to apoptosis and prevents loss of cardiolipin and cytochrome c release.
CC       {ECO:0000269|PubMed:11397793, ECO:0000269|PubMed:15347644}.
CC   -!- ACTIVITY REGULATION: The 2Fe-2S present in the homodimer leads to
CC       inactivation of the enzyme. The 2Fe-2S may serve as a redox sensor: the
CC       presence of one-electron oxidants or reductants leading to the loss of
CC       the 2Fe-2S cluster, subsequent monomerization and activation of the
CC       enzyme (By similarity). {ECO:0000250}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=1.68 mM for HEDS {ECO:0000269|PubMed:11397793};
CC         KM=1.77 mM for S-sulfocysteine {ECO:0000269|PubMed:11397793};
CC         KM=0.3 mM for L-cystine {ECO:0000269|PubMed:11397793};
CC   -!- SUBUNIT: Monomer; active form. Homodimer; inactive form. The homodimer
CC       is probably linked by 1 2Fe-2S cluster (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=Grx2a;
CC         IsoId=Q923X4-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q923X4-2; Sequence=VSP_015222;
CC   -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in testis, and
CC       at much lower level in kidney and brain. {ECO:0000269|PubMed:12954614}.
CC   -!- DEVELOPMENTAL STAGE: During development, it is expressed at highest
CC       level at 11 dpc. {ECO:0000269|PubMed:12954614}.
CC   -!- SIMILARITY: Belongs to the glutaredoxin family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAF86465.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AF380337; AAK85319.1; -; mRNA.
DR   EMBL; AF276918; AAF86465.1; ALT_FRAME; mRNA.
DR   EMBL; AK005853; BAB24276.1; -; mRNA.
DR   CCDS; CCDS15343.1; -. [Q923X4-1]
DR   CCDS; CCDS15344.1; -. [Q923X4-2]
DR   RefSeq; NP_001033681.1; NM_001038592.1. [Q923X4-1]
DR   RefSeq; NP_001033682.1; NM_001038593.1. [Q923X4-2]
DR   RefSeq; NP_001033683.1; NM_001038594.1. [Q923X4-2]
DR   RefSeq; NP_075994.2; NM_023505.2. [Q923X4-2]
DR   RefSeq; XP_006529919.1; XM_006529856.2. [Q923X4-2]
DR   AlphaFoldDB; Q923X4; -.
DR   SMR; Q923X4; -.
DR   BioGRID; 213390; 15.
DR   STRING; 10090.ENSMUSP00000141022; -.
DR   iPTMnet; Q923X4; -.
DR   PhosphoSitePlus; Q923X4; -.
DR   SwissPalm; Q923X4; -.
DR   EPD; Q923X4; -.
DR   MaxQB; Q923X4; -.
DR   PaxDb; 10090-ENSMUSP00000141022; -.
DR   ProteomicsDB; 266818; -. [Q923X4-1]
DR   ProteomicsDB; 266819; -. [Q923X4-2]
DR   Pumba; Q923X4; -.
DR   DNASU; 69367; -.
DR   Ensembl; ENSMUST00000111957.10; ENSMUSP00000107588.4; ENSMUSG00000018196.19. [Q923X4-2]
DR   Ensembl; ENSMUST00000129653.3; ENSMUSP00000121010.2; ENSMUSG00000018196.19. [Q923X4-2]
DR   Ensembl; ENSMUST00000145969.8; ENSMUSP00000121665.2; ENSMUSG00000018196.19. [Q923X4-2]
DR   Ensembl; ENSMUST00000185362.7; ENSMUSP00000141022.2; ENSMUSG00000018196.19. [Q923X4-1]
DR   GeneID; 69367; -.
DR   KEGG; mmu:69367; -.
DR   UCSC; uc007cwz.1; mouse. [Q923X4-1]
DR   AGR; MGI:1916617; -.
DR   CTD; 51022; -.
DR   MGI; MGI:1916617; Glrx2.
DR   VEuPathDB; HostDB:ENSMUSG00000018196; -.
DR   eggNOG; KOG1752; Eukaryota.
DR   GeneTree; ENSGT00940000167705; -.
DR   HOGENOM; CLU_026126_7_2_1; -.
DR   InParanoid; Q923X4; -.
DR   OMA; INGNCVG; -.
DR   OrthoDB; 203654at2759; -.
DR   PhylomeDB; Q923X4; -.
DR   TreeFam; TF319627; -.
DR   BioGRID-ORCS; 69367; 1 hit in 78 CRISPR screens.
DR   ChiTaRS; Glrx2; mouse.
DR   PRO; PR:Q923X4; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; Q923X4; Protein.
DR   Bgee; ENSMUSG00000018196; Expressed in ventricular zone and 257 other cell types or tissues.
DR   ExpressionAtlas; Q923X4; baseline and differential.
DR   GO; GO:0030425; C:dendrite; ISO:MGI.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR   GO; GO:0005759; C:mitochondrial matrix; ISO:MGI.
DR   GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR   GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0015035; F:protein-disulfide reductase activity; IDA:MGI.
DR   GO; GO:0042542; P:response to hydrogen peroxide; ISS:UniProtKB.
DR   GO; GO:0010033; P:response to organic substance; ISS:UniProtKB.
DR   CDD; cd03419; GRX_GRXh_1_2_like; 1.
DR   Gene3D; 3.40.30.10; Glutaredoxin; 1.
DR   InterPro; IPR002109; Glutaredoxin.
DR   InterPro; IPR011899; Glutaredoxin_euk/vir.
DR   InterPro; IPR014025; Glutaredoxin_subgr.
DR   InterPro; IPR036249; Thioredoxin-like_sf.
DR   NCBIfam; TIGR02180; GRX_euk; 1.
DR   PANTHER; PTHR46679; -; 1.
DR   PANTHER; PTHR46679:SF1; GLUTAREDOXIN-2, MITOCHONDRIAL; 1.
DR   Pfam; PF00462; Glutaredoxin; 1.
DR   PRINTS; PR00160; GLUTAREDOXIN.
DR   SUPFAM; SSF52833; Thioredoxin-like; 1.
DR   PROSITE; PS51354; GLUTAREDOXIN_2; 1.
DR   Genevisible; Q923X4; MM.
PE   1: Evidence at protein level;
KW   2Fe-2S; Alternative splicing; Disulfide bond; Electron transport;
KW   Glutathionylation; Iron; Iron-sulfur; Metal-binding; Mitochondrion;
KW   Nucleus; Redox-active center; Reference proteome; Transit peptide;
KW   Transport.
FT   TRANSIT         1..19
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           20..156
FT                   /note="Glutaredoxin-2, mitochondrial"
FT                   /id="PRO_0000011629"
FT   DOMAIN          50..150
FT                   /note="Glutaredoxin"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00686"
FT   BINDING         61
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in inactive form"
FT                   /evidence="ECO:0000250"
FT   BINDING         67
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000250"
FT   BINDING         102
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000250"
FT   BINDING         114
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000250"
FT   BINDING         146
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in inactive form"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         70
FT                   /note="S-glutathionyl cysteine; alternate"
FT                   /evidence="ECO:0000250"
FT   DISULFID        70..73
FT                   /note="Redox-active; alternate"
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         1..33
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072, ECO:0000303|Ref.2"
FT                   /id="VSP_015222"
SQ   SEQUENCE   156 AA;  17307 MW;  605BA5C62A139C3E CRC64;
     MSWRRAASVG RRLVASGRIL AGRRGAAGAA GSGMGNSTSS FWGKSTTTPV NQIQETISNN
     CVVIFSKTSC SYCSMAKKIF HDMNVNYKAV ELDMLEYGNQ FQDALHKMTG ERTVPRIFVN
     GRFIGGAADT HRLHKEGKLL PLVHQCYLKK KQEERH
//