GLRX2_MOUSE
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 03-AUG-2022, entry version 148.
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; Q923X4; -.
DR PRIDE; Q923X4; -.
DR ProteomicsDB; 266818; -. [Q923X4-1]
DR ProteomicsDB; 266819; -. [Q923X4-2]
DR DNASU; 69367; -.
DR Ensembl; ENSMUST00000111957; ENSMUSP00000107588; ENSMUSG00000018196. [Q923X4-2]
DR Ensembl; ENSMUST00000129653; ENSMUSP00000121010; ENSMUSG00000018196. [Q923X4-2]
DR Ensembl; ENSMUST00000145969; ENSMUSP00000121665; ENSMUSG00000018196. [Q923X4-2]
DR Ensembl; ENSMUST00000185362; ENSMUSP00000141022; ENSMUSG00000018196. [Q923X4-1]
DR GeneID; 69367; -.
DR KEGG; mmu:69367; -.
DR UCSC; uc007cwz.1; mouse. [Q923X4-1]
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; DSTHAQF; -.
DR PhylomeDB; Q923X4; -.
DR TreeFam; TF319627; -.
DR BioGRID-ORCS; 69367; 1 hit in 73 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 254 other tissues.
DR ExpressionAtlas; Q923X4; baseline and differential.
DR Genevisible; Q923X4; MM.
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:0097573; F:glutathione oxidoreductase activity; IEA:InterPro.
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 InterPro; IPR002109; Glutaredoxin.
DR InterPro; IPR011899; Glutaredoxin_euk/vir.
DR InterPro; IPR014025; Glutaredoxin_subgr.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR Pfam; PF00462; Glutaredoxin; 1.
DR PRINTS; PR00160; GLUTAREDOXIN.
DR SUPFAM; SSF52833; SSF52833; 1.
DR TIGRFAMs; TIGR02180; GRX_euk; 1.
DR PROSITE; PS51354; GLUTAREDOXIN_2; 1.
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
