GRX3 monothiol glutaredoxin GRX3 [ Saccharomyces cerevisiae S288C ]

Gene ID: 851672, updated on 30-Jul-2025

Official Symbol: GRX3
Official Full Name: monothiol glutaredoxin GRX3
Primary source: SGD:S000002505
Locus tag: YDR098C
See related: AllianceGenome:SGD:S000002505; FungiDB:YDR098C; VEuPathDB:YDR098C
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Saccharomyces cerevisiae S288C (strain: S288C)
Lineage: Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces
Summary: Enables RNA polymerase II-specific DNA-binding transcription factor binding activity; disulfide oxidoreductase activity; and iron-sulfur cluster binding activity. Involved in actin cytoskeleton organization and intracellular iron ion homeostasis. Located in cytosol and nucleus. Orthologous to human GLRX3 (glutaredoxin 3). [provided by Alliance of Genome Resources, Jul 2025]
Orthologs: all
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Genomic context

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See GRX3 in Genome Data Viewer

Location:: chromosome: IV

Exon count:: 1

Sequence:: Chromosome: IV; NC_001136.10 (644178..644930, complement)

Chromosome IV - NC_001136.10Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001136.10

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Genetic suppressors of Deltagrx3 Deltagrx4, lacking redundant multidomain monothiol yeast glutaredoxins, rescue growth and iron homeostasis.
Title: Genetic suppressors of Δgrx3 Δgrx4, lacking redundant multidomain monothiol yeast glutaredoxins, rescue growth and iron homeostasis.
Interactions of GMP with Human Glrx3 and with Saccharomyces cerevisiae Grx3 and Grx4 Converge in the Regulation of the Gcn2 Pathway.
Title: Interactions of GMP with Human Glrx3 and with Saccharomyces cerevisiae Grx3 and Grx4 Converge in the Regulation of the Gcn2 Pathway.
The conserved CDC motif in the yeast iron regulator Aft2 mediates iron-sulfur cluster exchange and protein-protein interactions with Grx3 and Bol2
Title: The conserved CDC motif in the yeast iron regulator Aft2 mediates iron-sulfur cluster exchange and protein-protein interactions with Grx3 and Bol2.
Study reports the crystal structure of both the Trx and Grx domains of Grx3, which enabled to model its full-length structure with an inter-domain disulfide bond. Despite the Trx domain alone losses the typical Trx activity, it significantly augments the glutathione S-transferases activity of the Grx domain, most likely via the interdomain disulfide bond. Also, Grx3 cooperates with Fra2 to regulate the activity of Atf2.
Title: Structural and Biochemical Insights into the Multiple Functions of Yeast Grx3.
We provide new mechanistic insights into Grx3/4 regulation of Sir2 by S-deglutathionylation to increase cell resistance to stress. This finding offers news perspectives on monothiol Grxs in redox signaling, describing Sir2 as a physiological substrate regulated by S-glutathionylation.
Title: Reversible glutathionylation of Sir2 by monothiol glutaredoxins Grx3/4 regulates stress resistance.
Slt2 form iron/sulphur bridged clusters with Grx3 and Grx4.
Title: Physical interaction between the MAPK Slt2 of the PKC1-MAPK pathway and Grx3/Grx4 glutaredoxins is required for the oxidative stress response in budding yeast.
This article reports mechanistic studies that investigate the role of exogenous glutathione in defining cluster chirality, ligand exchange, and the cluster transfer chemistry of Saccharomyces cerevisiae Grx3.
Title: Role of protein-glutathione contacts in defining glutaredoxin-3 [2Fe-2S] cluster chirality, ligand exchange and transfer chemistry.
RNR cofactor biogenesis requires the ISC machinery to mature the Grx3/4 and Dre2 Fe-S proteins, which then function in iron and electron delivery to RNR, respectively.
Title: The diferric-tyrosyl radical cluster of ribonucleotide reductase and cytosolic iron-sulfur clusters have distinct and similar biogenesis requirements.
diferric tyrosyl radical formation in Saccharomyces cerevisiae Rnr2 protein: requirement of Rnr4 and contribution of Grx3/4 AND Dre2 proteins.(
Title: Investigation of in vivo diferric tyrosyl radical formation in Saccharomyces cerevisiae Rnr2 protein: requirement of Rnr4 and contribution of Grx3/4 AND Dre2 proteins.
The authors present data showing that both Grx3 and Grx4 have roles in actin cytoskeleton remodeling and in cellular defenses against oxidative stress caused by reactive oxygen species (ROS) accumulation.
Title: Glutaredoxins Grx4 and Grx3 of Saccharomyces cerevisiae play a role in actin dynamics through their Trx domains, which contributes to oxidative stress resistance.

Submit: New GeneRIF Correction See all GeneRIFs (13)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by SGD

Function	Evidence Code	Pubs
enables 2 iron, 2 sulfur cluster binding	IBA Inferred from Biological aspect of Ancestor more info
enables 2 iron, 2 sulfur cluster binding	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II-specific DNA-binding transcription factor binding	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II-specific DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables disulfide oxidoreductase activity	IEA Inferred from Electronic Annotation more info
enables disulfide oxidoreductase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables iron-sulfur cluster binding	IDA Inferred from Direct Assay more info	PubMed
enables iron-sulfur cluster binding	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in actin cytoskeleton organization	IEA Inferred from Electronic Annotation more info
involved_in actin cytoskeleton organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular iron ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular iron ion homeostasis	IEA Inferred from Electronic Annotation more info
involved_in intracellular iron ion homeostasis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in intracellular iron ion homeostasis	IPI Inferred from Physical Interaction more info	PubMed
involved_in intracellular iron ion homeostasis	NAS Non-traceable Author Statement more info	PubMed
involved_in iron-sulfur cluster assembly	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	NAS Non-traceable Author Statement more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
part_of iron-sulfur cluster assembly complex	IEA Inferred from Electronic Annotation more info
part_of iron-sulfur cluster assembly complex	IPI Inferred from Physical Interaction more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: monothiol glutaredoxin GRX3

NP_010383.4

Glutathione-dependent oxidoreductase; hydroperoxide and superoxide-radical responsive monothiol glutaredoxin subfamily member with Grx4p and Grx5p; redundantly protects cells from oxidative damage along with GRX4 and GRX5; with Grx4p, promotes the dissociation of Aft1p from iron regulon gene promoters and subsequent nuclear export in iron-replete conditions, regulating iron homeostasis; involved with Grx4p in the deglutathionylation of Sir2p, restoring deacetylase activity after disulfide stress

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

This section includes genomic Reference Sequences (RefSeqs) from all assemblies on which this gene is annotated, such as RefSeqs for chromosomes and scaffolds (contigs) from both reference and alternate assemblies. Model RNAs and proteins are also reported here.

Reference assembly

Genomic

NC_001136.10 Reference assembly

Range

644178..644930 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001180406.4 → NP_010383.4 TPA: monothiol glutaredoxin GRX3

See identical proteins and their annotated locations for NP_010383.4

Status: REVIEWED

UniProtKB/Swiss-Prot

D6VS83, Q03835

UniProtKB/TrEMBL

N1P6A9

Conserved Domains (2) summary

cd02984
Location:9 → 106

TRX_PICOT; TRX domain, PICOT (for PKC-interacting cousin of TRX) subfamily; PICOT is a protein that interacts with protein kinase C (PKC) theta, a calcium independent PKC isoform selectively expressed in skeletal muscle and T lymphocytes. PICOT contains an ...

cd03028
Location:154 → 238

GRX_PICOT_like; Glutaredoxin (GRX) family, PKC-interacting cousin of TRX (PICOT)-like subfamily; composed of PICOT and GRX-PICOT-like proteins. The non-PICOT members of this family contain only the GRX-like domain, whereas PICOT contains an N-terminal TRX-like domain ...