ID   GLRX3_DANRE             Reviewed;         326 AA.
AC   Q5XJ54;
DT   02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT   23-NOV-2004, sequence version 1.
DT   03-AUG-2022, entry version 109.
DE   RecName: Full=Glutaredoxin 3;
GN   Name=glrx3; Synonyms=txnl2;
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;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Larva;
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=23615448; DOI=10.1091/mbc.e12-09-0648;
RA   Haunhorst P., Hanschmann E.M., Brautigam L., Stehling O., Hoffmann B.,
RA   Muhlenhoff U., Lill R., Berndt C., Lillig C.H.;
RT   "Crucial function of vertebrate glutaredoxin 3 (PICOT) in iron homeostasis
RT   and hemoglobin maturation.";
RL   Mol. Biol. Cell 24:1895-1903(2013).
CC   -!- FUNCTION: Together with bola2, acts as a cytosolic iron-sulfur (Fe-S)
CC       cluster assembly factor that facilitates [2Fe-2S] cluster insertion
CC       into a subset of cytosolic proteins (By similarity). Required for
CC       hemoglobin maturation (PubMed:23615448). Does not possess any
CC       thyoredoxin activity since it lacks the conserved motif that is
CC       essential for catalytic activity (By similarity).
CC       {ECO:0000250|UniProtKB:O76003, ECO:0000250|UniProtKB:Q9CQM9,
CC       ECO:0000269|PubMed:23615448}.
CC   -!- SUBUNIT: Homodimer; the homodimer is independent of 2Fe-2S clusters.
CC       Heterotrimer; forms a heterotrimeric complex composed by two bola2
CC       molecules and one glrx3 molecule; linked by [2Fe-2S] clusters.
CC       {ECO:0000250|UniProtKB:O76003, ECO:0000250|UniProtKB:Q9CQM9}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:O76003}.
CC   -!- DOMAIN: The thioredoxin domain lacks the two redox-active cysteines.
CC       This strongly suggests that it lacks thioredoxin activity.
CC   -!- DISRUPTION PHENOTYPE: Morpholino knockdown in embryos reducing the
CC       levels of grx3 protein to 40% severely impairs the synthesis of heme
CC       and the maturation of hemoglobin, and results in individuals with fewer
CC       red blood cells. {ECO:0000269|PubMed:23615448}.
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; BC083453; AAH83453.1; -; mRNA.
DR   EMBL; BC153570; AAI53571.1; -; mRNA.
DR   RefSeq; NP_001005950.1; NM_001005950.1.
DR   AlphaFoldDB; Q5XJ54; -.
DR   SMR; Q5XJ54; -.
DR   STRING; 7955.ENSDARP00000040389; -.
DR   PaxDb; Q5XJ54; -.
DR   GeneID; 449777; -.
DR   KEGG; dre:449777; -.
DR   CTD; 10539; -.
DR   ZFIN; ZDB-GENE-041010-22; glrx3.
DR   eggNOG; KOG0911; Eukaryota.
DR   InParanoid; Q5XJ54; -.
DR   OrthoDB; 1449534at2759; -.
DR   PhylomeDB; Q5XJ54; -.
DR   PRO; PR:Q5XJ54; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Unplaced.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0097573; F:glutathione oxidoreductase activity; IEA:InterPro.
DR   GO; GO:0051536; F:iron-sulfur cluster binding; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0006879; P:cellular iron ion homeostasis; IBA:GO_Central.
DR   GO; GO:0020027; P:hemoglobin metabolic process; IMP:ZFIN.
DR   GO; GO:0055072; P:iron ion homeostasis; IMP:ZFIN.
DR   CDD; cd03028; GRX_PICOT_like; 2.
DR   InterPro; IPR002109; Glutaredoxin.
DR   InterPro; IPR033658; GRX_PICOT-like.
DR   InterPro; IPR004480; Monothiol_GRX-rel.
DR   InterPro; IPR036249; Thioredoxin-like_sf.
DR   InterPro; IPR013766; Thioredoxin_domain.
DR   PANTHER; PTHR10293; PTHR10293; 1.
DR   Pfam; PF00462; Glutaredoxin; 2.
DR   Pfam; PF00085; Thioredoxin; 1.
DR   SUPFAM; SSF52833; SSF52833; 3.
DR   TIGRFAMs; TIGR00365; TIGR00365; 2.
DR   PROSITE; PS51354; GLUTAREDOXIN_2; 2.
DR   PROSITE; PS51352; THIOREDOXIN_2; 1.
PE   2: Evidence at transcript level;
KW   Cytoplasm; Iron; Iron-sulfur; Metal-binding; Reference proteome; Repeat.
FT   CHAIN           1..326
FT                   /note="Glutaredoxin 3"
FT                   /id="PRO_0000348927"
FT   DOMAIN          1..108
FT                   /note="Thioredoxin"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DOMAIN          125..227
FT                   /note="Glutaredoxin 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00686"
FT   DOMAIN          227..326
FT                   /note="Glutaredoxin 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00686"
FT   BINDING         150
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:O76003"
FT   BINDING         252
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:O76003"
SQ   SEQUENCE   326 AA;  36335 MW;  2DC664A390D94FD5 CRC64;
     MANFTDAASL QQFDELLKNN SKSLTVVHFH APWAPQCSQM NDVMAELAKE HKHTMFVKLE
     AEAVPEVSEK YEITSVPTFL FFKGGEKIDR LDGAHAPELT NKVQRLGSGG GGAVGAGDVP
     KEDLNQRLKR LINAAPCMLF MKGSPQEPRC GFSRQIIQIL KDHNVQYSSF DILSDEEVRQ
     GLKTYSNWPT YPQVYVSGEL IGGLDIVKEL VESGELENTF PKTVSLENRL KSLINKSPVM
     LFMKGNKEAA KCGFSRQILE IMNNTGVEYD TFDILEDEEV RQGLKTYSNW PTFPQLYVKG
     DLIGGLDIVK ELLEGGELVS VLKGEN