GLRX2 glutaredoxin 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GLRX2provided by HGNC
Official Full Name: glutaredoxin 2provided by HGNC
Primary source: HGNC:HGNC:16065
See related: Ensembl:ENSG00000023572 MIM:606820; AllianceGenome:HGNC:16065
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GRX2; CGI-133
Summary: The protein encoded by this gene is a member of the glutaredoxin family of proteins, which maintain cellular thiol homeostasis. These proteins are thiol-disulfide oxidoreductases that use a glutathione-binding site and one or two active cysteines in their active site. This gene undergoes alternative splicing to produce multiple isoforms, one of which is ubiquitously expressed and localizes to mitochondria, where it functions in mitochondrial redox homeostasis and is important for the protection against and recovery from oxidative stress. Other isoforms, which have more restrictive expression patterns, show cytosolic and nuclear localization, and are thought to function in cellular differentiation and transformation, possibly with a role in tumor progression. [provided by RefSeq, Aug 2011]
Expression: Broad expression in testis (RPKM 15.8), prostate (RPKM 7.2) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q31.2

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (193096465..193106114, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (192443673..192453323, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (193065595..193075244, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Glutaredoxin 2 Protein (Grx2) as an Independent Prognostic Factor Associated with the Survival of Colon Adenocarcinoma Patients.
Title: Glutaredoxin 2 Protein (Grx2) as an Independent Prognostic Factor Associated with the Survival of Colon Adenocarcinoma Patients.
By sensing the overall cellular redox conditions, mitochondrial Grx2 dimers become active monomers upon oxidative stress induced by sodium selenite with the consequent release of the iron-sulfur cluster, leading to activation of the intrinsic apoptotic pathway.
Title: Dimers of glutaredoxin 2 as mitochondrial redox sensors in selenite-induced oxidative stress.
GRX2 is important in the control of cardiac mitochondrial structure and function, and protects against human cardiac pathologies.
Title: Glutaredoxin-2 controls cardiac mitochondrial dynamics and energetics in mice, and protects against human cardiac pathologies.
Study shows that Grx2 detoxifies *NO in mature oligodendrocytes and oligodendroglial precursor cellsvia the formation of dinitrosyl-iron-complexes, inhibiting the formation of harmful peroxynitrite and reducing subsequent oligodendroglial damage. Findings link inorganic biochemistry to neuroinflammation and identify glutaredoxin 2 as a protective factor against neuroinflammation-mediated myelin damage.
Title: Iron-sulfur glutaredoxin 2 protects oligodendrocytes against damage induced by nitric oxide release from activated microglia.
Grx2 and Trx1 contribute significantly to neuronal integrity and could be clinically relevant in neuronal damage following perinatal asphyxia and other neuronal disorders.
Title: Thioredoxin 1 and glutaredoxin 2 contribute to maintain the phenotype and integrity of neurons following perinatal asphyxia.
The Grx2 system could help to keep Trx2/1 reduced during an oxidative stress, thereby contributing to the anti-apoptotic signaling.
Title: Glutaredoxin 2 reduces both thioredoxin 2 and thioredoxin 1 and protects cells from apoptosis induced by auranofin and 4-hydroxynonenal.
These results suggest that Grx2a plays proliferative and anti-apoptotic roles under serum deprivation.
Title: Glutaredoxin 2a, a mitochondrial isoform, plays a protective role in a human cell line under serum deprivation.
Grx2 thiol redox regulation is essential for vertebrate embryonic development
Title: Vertebrate-specific glutaredoxin is essential for brain development.
Exchange of [2Fe-2S] centers between glutaredoxin 2 and the cluster scaffold protein ISU, supports a direct link for glutaredoxin 2 and glutathione involvement in ISU promoted Fe-S cluster biosynthesis.
Title: Mechanism of glutaredoxin-ISU [2Fe-2S] cluster exchange.
Both thioredoxin 2 and glutaredoxin 2 contribute to the reduction of the mitochondrial 2-Cys peroxiredoxin Prx3.
Title: Both thioredoxin 2 and glutaredoxin 2 contribute to the reduction of the mitochondrial 2-Cys peroxiredoxin Prx3.

Submit: New GeneRIF Correction See all GeneRIFs (23)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
retropepsin	gag-pol	Treatment of diglutathionylated HIV-1 protease (positions 67 and 95) with thioltransferase (glutaredoxin) restores protease activity and generates an enzyme preparation that has 3- to 5-fold greater specific activity relative to the fully reduced form	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-146669 (e-PCR)
- UniSTS:172655

SHGC-32745 (e-PCR)
- UniSTS:2493

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 2 iron, 2 sulfur cluster binding	IEA Inferred from Electronic Annotation more info
enables arsenate reductase (glutaredoxin) activity	TAS Traceable Author Statement more info	PubMed
enables electron transfer activity	NAS Non-traceable Author Statement more info	PubMed
enables glutathione disulfide oxidoreductase activity	TAS Traceable Author Statement more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein disulfide isomerase activity	TAS Traceable Author Statement more info	PubMed
enables protein-disulfide reductase activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in DNA protection	NAS Non-traceable Author Statement more info	PubMed
involved_in apoptotic process	NAS Non-traceable Author Statement more info	PubMed
involved_in cell differentiation	NAS Non-traceable Author Statement more info	PubMed
involved_in cell redox homeostasis	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to superoxide	IEA Inferred from Electronic Annotation more info
involved_in glutathione metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in regulation of DNA-templated transcription	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of signal transduction	NAS Non-traceable Author Statement more info	PubMed
involved_in response to redox state	TAS Traceable Author Statement more info	PubMed
involved_in response to temperature stimulus	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in dendrite	IEA Inferred from Electronic Annotation more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in mitochondrial matrix	IEA Inferred from Electronic Annotation more info
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: glutaredoxin 2

Names: bA101E13.1 (GRX2 glutaredoxin (thioltransferase) 2); glutaredoxin (thioltransferase) 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029745.1 RefSeqGene

Range

5701..14645

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001243399.2 → NP_001230328.1 glutaredoxin 2 isoform 3

See identical proteins and their annotated locations for NP_001230328.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream in-frame start codon, compared to variant 1. The encoded isoform (3, also known as Grx2c) is shorter at the N-terminus, compared to isoform 1.

Source sequence(s)

AA056513, AA887118, BQ432881

UniProtKB/Swiss-Prot

Q9NS18

Conserved Domains (1) summary

cd03419
Location:28 → 109

GRX_GRXh_1_2_like; Glutaredoxin (GRX) family, GRX human class 1 and 2 (h_1_2)-like subfamily; composed of proteins similar to human GRXs, approximately 10 kDa in size, and proteins containing a GRX or GRX-like domain. GRX is a glutathione (GSH) dependent reductase, ...
NM_016066.4 → NP_057150.2 glutaredoxin 2 isoform 1

See identical proteins and their annotated locations for NP_057150.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1, also known as Grx2b).

Source sequence(s)

AA056513, AF290514

Consensus CDS

CCDS1380.1

UniProtKB/Swiss-Prot

Q9NS18

Related

ENSP00000356410.3, ENST00000367440.3

Conserved Domains (1) summary

cd03419
Location:69 → 150

GRX_GRXh_1_2_like; Glutaredoxin (GRX) family, GRX human class 1 and 2 (h_1_2)-like subfamily; composed of proteins similar to human GRXs, approximately 10 kDa in size, and proteins containing a GRX or GRX-like domain. GRX is a glutathione (GSH) dependent reductase, ...
NM_197962.3 → NP_932066.1 glutaredoxin 2 isoform 2 precursor

See identical proteins and their annotated locations for NP_932066.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate 5' exon and thus differs in the 5' UTR and 5' coding region, compared to variant 1. The encoded isoform (2, also known as Grx2a or mitochondrial Grx2) has a distinct N-terminus and is shorter than isoform 1.

Source sequence(s)

AY038988, CN362908

Consensus CDS

CCDS1381.1

UniProtKB/Swiss-Prot

Q3LR69, Q7L1N7, Q96JC0, Q9NS18, Q9Y3D4

UniProtKB/TrEMBL

A0JLT0

Related

ENSP00000356409.3, ENST00000367439.8

Conserved Domains (1) summary

cd03419
Location:68 → 149

GRX_GRXh_1_2_like; Glutaredoxin (GRX) family, GRX human class 1 and 2 (h_1_2)-like subfamily; composed of proteins similar to human GRXs, approximately 10 kDa in size, and proteins containing a GRX or GRX-like domain. GRX is a glutathione (GSH) dependent reductase, ...