ID   Q6DH06_DANRE            Unreviewed;       134 AA.
AC   Q6DH06;
DT   16-AUG-2004, integrated into UniProtKB/TrEMBL.
DT   16-AUG-2004, sequence version 1.
DT   27-MAR-2024, entry version 144.
DE   RecName: Full=Glutaredoxin-2, mitochondrial {ECO:0000256|ARBA:ARBA00039819};
GN   Name=glrx2 {ECO:0000313|EMBL:AAH76178.1,
GN   ECO:0000313|ZFIN:ZDB-GENE-040718-101};
GN   Synonyms=zgc:92698 {ECO:0000313|RefSeq:NP_001002404.1,
GN   ECO:0000313|RefSeq:XP_009294644.1};
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955 {ECO:0000313|EMBL:AAH76178.1};
RN   [1] {ECO:0000313|EMBL:AAH76178.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Eye {ECO:0000313|EMBL:AAH76178.1};
RA   Tajne S.S.;
RL   Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN   [2] {ECO:0000313|RefSeq:NP_001002404.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=22139372;
RA   Brautigam L., Schutte L.D., Godoy J.R., Prozorovski T., Gellert M.,
RA   Hauptmann G., Holmgren A., Lillig C.H., Berndt C.;
RT   "Vertebrate-specific glutaredoxin is essential for brain development.";
RL   Proc. Natl. Acad. Sci. U.S.A. 108:20532-20537(2011).
RN   [3] {ECO:0007829|PDB:3UIW}
RP   X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE, AND
RP   DISULFIDE BONDS.
RA   Brautigam L., Johansson C., Kubsch B., McDonough M.A., Bill E.,
RA   Holmgren A., Berndt C.;
RT   "A New Mode of Iron-sulfur Cluster Coordination in Glutaredoxins is Crucial
RT   for Axonogenesis.";
RL   Submitted (NOV-2011) to the PDB data bank.
RN   [4] {ECO:0000313|RefSeq:NP_001002404.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=23756812;
RA   Brautigam L., Johansson C., Kubsch B., McDonough M.A., Bill E.,
RA   Holmgren A., Berndt C.;
RT   "An unusual mode of iron-sulfur-cluster coordination in a teleost
RT   glutaredoxin.";
RL   Biochem. Biophys. Res. Commun. 436:491-496(2013).
RN   [5] {ECO:0000313|Proteomes:UP000000437}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=23594743; DOI=10.1038/nature12111;
RG   Genome Reference Consortium Zebrafish;
RA   Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA   Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA   Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA   White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA   Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA   Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA   Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA   Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA   Clee C., Oliver K., Clark R., Riddle C., Elliot D., Eliott D.,
RA   Threadgold G., Harden G., Ware D., Begum S., Mortimore B., Mortimer B.,
RA   Kerry G., Heath P., Phillimore B., Tracey A., Corby N., Dunn M.,
RA   Johnson C., Wood J., Clark S., Pelan S., Griffiths G., Smith M.,
RA   Glithero R., Howden P., Barker N., Lloyd C., Stevens C., Harley J.,
RA   Holt K., Panagiotidis G., Lovell J., Beasley H., Henderson C., Gordon D.,
RA   Auger K., Wright D., Collins J., Raisen C., Dyer L., Leung K.,
RA   Robertson L., Ambridge K., Leongamornlert D., McGuire S., Gilderthorp R.,
RA   Griffiths C., Manthravadi D., Nichol S., Barker G., Whitehead S., Kay M.,
RA   Brown J., Murnane C., Gray E., Humphries M., Sycamore N., Barker D.,
RA   Saunders D., Wallis J., Babbage A., Hammond S., Mashreghi-Mohammadi M.,
RA   Barr L., Martin S., Wray P., Ellington A., Matthews N., Ellwood M.,
RA   Woodmansey R., Clark G., Cooper J., Cooper J., Tromans A., Grafham D.,
RA   Skuce C., Pandian R., Andrews R., Harrison E., Kimberley A., Garnett J.,
RA   Fosker N., Hall R., Garner P., Kelly D., Bird C., Palmer S., Gehring I.,
RA   Berger A., Dooley C.M., Ersan-Urun Z., Eser C., Geiger H., Geisler M.,
RA   Karotki L., Kirn A., Konantz J., Konantz M., Oberlander M.,
RA   Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G., Osoegawa K., Zhu B.,
RA   Rapp A., Widaa S., Langford C., Yang F., Schuster S.C., Carter N.P.,
RA   Harrow J., Ning Z., Herrero J., Searle S.M., Enright A., Geisler R.,
RA   Plasterk R.H., Lee C., Westerfield M., de Jong P.J., Zon L.I.,
RA   Postlethwait J.H., Nusslein-Volhard C., Hubbard T.J., Roest Crollius H.,
RA   Rogers J., Stemple D.L.;
RT   "The zebrafish reference genome sequence and its relationship to the human
RT   genome.";
RL   Nature 496:498-503(2013).
RN   [6] {ECO:0000313|RefSeq:NP_001002404.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=24277839;
RA   Brautigam L., Jensen L.D., Poschmann G., Nystrom S., Bannenberg S.,
RA   Dreij K., Lepka K., Prozorovski T., Montano S.J., Aktas O., Uhlen P.,
RA   Stuhler K., Cao Y., Holmgren A., Berndt C.;
RT   "Glutaredoxin regulates vascular development by reversible
RT   glutathionylation of sirtuin 1.";
RL   Proc. Natl. Acad. Sci. U.S.A. 110:20057-20062(2013).
RN   [7] {ECO:0000313|RefSeq:NP_001002404.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=24944912; DOI=10.1016/j.redox.2014.04.012;
RA   Berndt C., Poschmann G., Stuhler K., Holmgren A., Brautigam L.;
RT   "Zebrafish heart development is regulated via glutaredoxin 2 dependent
RT   migration and survival of neural crest cells.";
RL   Redox Biol. 2:673-678(2014).
RN   [8] {ECO:0000313|RefSeq:NP_001002404.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=26499117;
RA   Bui-Nguyen T.M., Baer C.E., Lewis J.A., Yang D., Lein P.J., Jackson D.A.;
RT   "Dichlorvos exposure results in large scale disruption of energy metabolism
RT   in the liver of the zebrafish, Danio rerio.";
RL   BMC Genomics 16:853-853(2015).
RN   [9] {ECO:0000313|RefSeq:NP_001002404.1}
RP   NUCLEOTIDE SEQUENCE.
RX   PubMed=27979767;
RA   Lin S.J., Chiang M.C., Shih H.Y., Hsu L.S., Yeh T.H., Huang Y.C., Lin C.Y.,
RA   Cheng Y.C.;
RT   "Regulator of G protein signaling 2 (Rgs2) regulates neural crest
RT   development through Ppardelta-Sox10 cascade.";
RL   Biochim. Biophys. Acta 1864:463-474(2017).
RN   [10] {ECO:0000313|RefSeq:NP_001002404.1, ECO:0000313|RefSeq:XP_009294644.1}
RP   IDENTIFICATION.
RC   STRAIN=Tuebingen {ECO:0000313|RefSeq:XP_009294644.1};
RG   RefSeq;
RL   Submitted (NOV-2023) to UniProtKB.
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:0000256|ARBA:ARBA00037470}.
CC   -!- FUNCTION: Has a glutathione-disulfide oxidoreductase activity in the
CC       presence of NADPH and glutathione reductase. Reduces low molecular
CC       weight disulfides and proteins. {ECO:0000256|ARBA:ARBA00002549}.
CC   -!- SUBUNIT: Monomer; active form. Homodimer; inactive form. The homodimer
CC       is probably linked by 1 2Fe-2S cluster.
CC       {ECO:0000256|ARBA:ARBA00038558}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000256|ARBA:ARBA00004173}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; BC076178; AAH76178.1; -; mRNA.
DR   RefSeq; NP_001002404.1; NM_001002404.1.
DR   RefSeq; XP_009294644.1; XM_009296369.3.
DR   PDB; 3UIW; X-ray; 2.60 A; A/B=1-134.
DR   PDBsum; 3UIW; -.
DR   GeneID; 436677; -.
DR   KEGG; dre:436677; -.
DR   AGR; ZFIN:ZDB-GENE-040718-101; -.
DR   CTD; 51022; -.
DR   ZFIN; ZDB-GENE-040718-101; glrx2.
DR   OrthoDB; 203654at2759; -.
DR   PhylomeDB; Q6DH06; -.
DR   Proteomes; UP000000437; Alternate scaffold 22.
DR   Proteomes; UP000000437; Chromosome 22.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IDA:ZFIN.
DR   GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR   GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IDA:ZFIN.
DR   GO; GO:0015038; F:glutathione disulfide oxidoreductase activity; IDA:ZFIN.
DR   GO; GO:0016491; F:oxidoreductase activity; IDA:ZFIN.
DR   GO; GO:0034599; P:cellular response to oxidative stress; IBA:GO_Central.
DR   GO; GO:0007417; P:central nervous system development; IMP:ZFIN.
DR   GO; GO:0008347; P:glial cell migration; IMP:ZFIN.
DR   GO; GO:0060914; P:heart formation; IMP:ZFIN.
DR   GO; GO:0001755; P:neural crest cell migration; IMP:ZFIN.
DR   GO; GO:0003147; P:neural crest cell migration involved in heart formation; IMP:ZFIN.
DR   GO; GO:0001944; P:vasculature development; IMP:ZFIN.
DR   CDD; cd03419; GRX_GRXh_1_2_like; 1.
DR   Gene3D; 3.40.30.10; Glutaredoxin; 1.
DR   InterPro; IPR011767; GLR_AS.
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; PS00195; GLUTAREDOXIN_1; 1.
DR   PROSITE; PS51354; GLUTAREDOXIN_2; 1.
PE   1: Evidence at protein level;
KW   2Fe-2S {ECO:0000256|ARBA:ARBA00022714};
KW   3D-structure {ECO:0007829|PDB:3UIW};
KW   Disulfide bond {ECO:0000256|ARBA:ARBA00023157};
KW   Electron transport {ECO:0000256|ARBA:ARBA00022982};
KW   Glutathionylation {ECO:0000256|ARBA:ARBA00023206};
KW   Iron {ECO:0000256|ARBA:ARBA00023004};
KW   Iron-sulfur {ECO:0000256|ARBA:ARBA00023014};
KW   Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW   Mitochondrion {ECO:0000256|ARBA:ARBA00023128};
KW   Proteomics identification {ECO:0007829|PeptideAtlas:Q6DH06};
KW   Redox-active center {ECO:0000256|ARBA:ARBA00023284};
KW   Reference proteome {ECO:0000313|Proteomes:UP000000437};
KW   Transit peptide {ECO:0000256|ARBA:ARBA00022946};
KW   Transport {ECO:0000256|ARBA:ARBA00022448}.
FT   DOMAIN          29..91
FT                   /note="Glutaredoxin"
FT                   /evidence="ECO:0000259|Pfam:PF00462"
FT   BINDING         34
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0007829|PDB:3UIW"
FT   BINDING         37
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /ligand_note="covalent"
FT                   /evidence="ECO:0007829|PDB:3UIW"
FT   BINDING         69
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0007829|PDB:3UIW"
FT   BINDING         81
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0007829|PDB:3UIW"
FT   BINDING         94
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0007829|PDB:3UIW"
FT   BINDING         95
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0007829|PDB:3UIW"
FT   DISULFID        28..113
FT                   /evidence="ECO:0007829|PDB:3UIW"
FT   DISULFID        116
FT                   /evidence="ECO:0007829|PDB:3UIW"
SQ   SEQUENCE   134 AA;  14408 MW;  DBF98B30628DA0BD CRC64;
     MGNFSSSAPG LSSSACGQFV QDIVSSNCVV IFSKTTCPYC KMAKGVFNEI GATYKVVELD
     EHNDGRRLQE TLAELTGART VPRVFINGQC IGGGSDTKQL HQQGKLLPLI EQCRPCCLNM
     TPEGSGNSQN QPHQ
//