GRX4 monothiol glutaredoxin GRX4 [Saccharomyces cerevisiae S288C] - Gene

Summary

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Gene symbol: GRX4
Gene description: monothiol glutaredoxin GRX4
Primary source: SGD:S000000976
Locus tag: YER174C
See related: AllianceGenome:SGD:S000000976
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 glutathione transferase activity. Involved in several processes, including cellular iron ion homeostasis; negative regulation of transcription regulatory region DNA binding activity; and positive regulation of histone deacetylation. Located in nucleus. Orthologous to human GLRX3 (glutaredoxin 3). [provided by Alliance of Genome Resources, Apr 2022]
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Genomic context

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Location:: chromosome: V

Exon count:: 1

Sequence:: Chromosome: V; NC_001137.3 (538434..539168, complement)

Chromosome V - NC_001137.3 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001137.3

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.
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.
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.
Sch9 phosphorylates, both in vitro and in vivo, Ser258 of Bud32. This modification does not affect the catalytic properties of Bud32, but promotes its ability to associate with its substrate Grx4p and, consequently, to phosphorylate it.
Title: Phosphorylation of the Saccharomyces cerevisiae Grx4p glutaredoxin by the Bud32p kinase unveils a novel signaling pathway involving Sch9p, a yeast member of the Akt / PKB subfamily.
Grx3 and Grx4 are novel components required for Aft1 iron regulation that most likely occurs in the nucleus
Title: Role of glutaredoxin-3 and glutaredoxin-4 in the iron regulation of the Aft1 transcriptional activator in Saccharomyces cerevisiae.

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

Orthologs from OrthoDB

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	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 glutathione transferase activity	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in actin cytoskeleton organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to oxidative stress	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	IGI Inferred from Genetic Interaction more info	PubMed
involved_in intracellular iron ion homeostasis	IPI Inferred from Physical Interaction more info	PubMed
involved_in negative regulation of transcription regulatory region DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: monothiol glutaredoxin GRX4

NP_011101.3

Glutathione-dependent oxidoreductase and glutathione S-transferase; hydroperoxide/superoxide-radical responsive monothiol glutaredoxin subfamily member with Grx3p and Grx5p; protects cells from oxidative damage with GRX3 and GRX5; with Grx3p, promotes dissociation of Aft1p from iron regulon gene promoters and subsequent nuclear export in iron-replete conditions, regulating iron homeostasis; involved with Grx3p in Sir2p deglutathionylation, 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

Reference assembly

Genomic

NC_001137.3 Reference assembly

Range

538434..539168 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001179064.3 → NP_011101.3 TPA: monothiol glutaredoxin GRX4 [Saccharomyces cerevisiae S288C]

See identical proteins and their annotated locations for NP_011101.3

Status: REVIEWED

UniProtKB/Swiss-Prot

D3DM82, P32642

UniProtKB/TrEMBL

A0A8H8UM37, A6ZRD0, B3LRT3, B5VHV5, C7GS36, G2WD60, N1P5G5

Conserved Domains (2) summary

cd02984
Location:8 → 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:149 → 233

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 ...