Txnrd2 thioredoxin reductase 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Txnrd2provided by MGI
Official Full Name: thioredoxin reductase 2provided by MGI
Primary source: MGI:MGI:1347023
See related: Ensembl:ENSMUSG00000075704 AllianceGenome:MGI:1347023
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: TGR; Tr3; Trxr2; Trxrd2; ESTM573010
Summary: The protein encoded by this gene belongs to the pyridine nucleotide-disulfide oxidoreductase family, and is a member of the thioredoxin (Trx) system. Three thioredoxin reductase (TrxR) isozymes are found in mammals. TrxRs are selenocysteine-containing flavoenzymes, which reduce thioredoxins, as well as other substrates, and play a key role in redox homoeostasis. This gene encodes a mitochondrial form important for scavenging reactive oxygen species in mitochondria. It functions as a homodimer containing FAD, and selenocysteine (Sec) at the active site. Sec is encoded by UGA codon that normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element, which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jun 2017]
Expression: Ubiquitous expression in liver E14.5 (RPKM 41.1), liver E14 (RPKM 39.1) and 27 other tissues See more
Orthologs: human all
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Genomic context

Location:: 16 A3; 16 11.41 cM

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	16	NC_000082.7 (18245167..18297823)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	16	NC_000082.6 (18426417..18479073)

Chromosome 16 - NC_000082.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Thioredoxin Reductase 2 Synergizes with Cytochrome c, Somatic to Alleviate Doxorubicin-Induced Oxidative Stress in Cardiomyocytes and Mouse Myocardium.
Title: Thioredoxin Reductase 2 Synergizes with Cytochrome c, Somatic to Alleviate Doxorubicin-Induced Oxidative Stress in Cardiomyocytes and Mouse Myocardium.
Mitochondrial TrxR2 regulates metabolism and protects from metabolic disease through enhanced TCA and ETC function.
Title: Mitochondrial TrxR2 regulates metabolism and protects from metabolic disease through enhanced TCA and ETC function.
Wogonin induces cellular senescence in breast cancer via suppressing TXNRD2 expression.
Title: Wogonin induces cellular senescence in breast cancer via suppressing TXNRD2 expression.
The mitochondrial thioredoxin reductase system (TrxR2) in vascular endothelium controls peroxynitrite levels and tissue integrity.
Title: The mitochondrial thioredoxin reductase system (TrxR2) in vascular endothelium controls peroxynitrite levels and tissue integrity.
Study identified a causal molecular mechanism that reflects diminished dosage of a single 22q11 gene-the mitochondrial enzyme thioredoxin-reductase 2 (Txnrd2)-essential for catabolism of reactive oxygen species underlies reduced long-distance projections, limited axon and dendrite growth, and disrupted mitochondrial and synaptic integrity in layer 2/3 in DiGeorge syndrome.
Title: Mitochondrial Dysfunction Leads to Cortical Under-Connectivity and Cognitive Impairment.
This was accompanied by decreased NADPH redox state and decreased activity of TXNRD2 in the mitochondria of the HEI-OC1 cells. Therefore, IDH2 functions as the principal source of NADPH for the mitochondrial thioredoxin antioxidant defense and plays an essential role in protecting hair cells and neurons against oxidative stress in the cochlea of male mice.
Title: Loss of IDH2 Accelerates Age-related Hearing Loss in Male Mice.
Maintenance of mitochondrial ROS via Txnrd2 in endothelial cells is necessary for an intact vascular homeostasis and remodeling. Txnrd2 plays a vitally important role in balancing mitochondrial ROS production in the endothelium.
Title: Endothelial Dysfunction, and A Prothrombotic, Proinflammatory Phenotype Is Caused by Loss of Mitochondrial Thioredoxin Reductase in Endothelium.
Suggest role for Txnrd2 in sustaining heart function during aging and suggest that Txnrd2 may be a modifier of heart failure.
Title: Heart-Specific Knockout of the Mitochondrial Thioredoxin Reductase (Txnrd2) Induces Metabolic and Contractile Dysfunction in the Aging Myocardium.
Regulatory link was discovered between mitochondrial Txnrd and the JNK-PHD2-Hif-1alpha axis, which highlights how the loss of Txnrd2 and the resulting altered mitochondrial redox balance impairs tumor growth as well as tumor-related angiogenesis.
Title: Knockout of mitochondrial thioredoxin reductase stabilizes prolyl hydroxylase 2 and inhibits tumor growth and tumor-derived angiogenesis.
Data suggest TXNRD1 and TXRNRD2 function at the top of a redox pyramid that governs the oxidation state of peroxiredoxins and other protein factors, thereby dictating a hierarchy of phenotypic responses to oxidative insults.
Title: Resolution of oxidative stress by thioredoxin reductase: Cysteine versus selenocysteine.

Submit: New GeneRIF Correction See all GeneRIFs (23)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Gene trapped (1)
Targeted (4) 1 citation
Endonuclease-mediated (1)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Txnrd2 (e-PCR), detects polymorphism
- UniSTS:265765

RH135722 (e-PCR)
- UniSTS:158767

Txnrd2 (e-PCR), detects polymorphism
- UniSTS:496814

Txnrd2 (e-PCR), detects polymorphism
- UniSTS:526000

Txnrd2 (e-PCR), detects polymorphism
- UniSTS:527593

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables flavin adenine dinucleotide binding	IEA Inferred from Electronic Annotation more info
enables oxidoreductase activity	IEA Inferred from Electronic Annotation more info
enables oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor	IEA Inferred from Electronic Annotation more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info
enables thioredoxin-disulfide reductase (NADPH) activity	IBA Inferred from Biological aspect of Ancestor more info
enables thioredoxin-disulfide reductase (NADPH) activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in cell redox homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell redox homeostasis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within heart development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within hemopoiesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to oxygen radical	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in axon	ISO Inferred from Sequence Orthology more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in dendrite	ISO Inferred from Sequence Orthology 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 mitochondrion	ISO Inferred from Sequence Orthology more info
located_in neuronal cell body	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: thioredoxin reductase 2, mitochondrial

Names: TR beta; thioredoxin reductase TR3

NP_001340072.1

EC 1.8.1.9

NP_038739.2

EC 1.8.1.9

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.

mRNA and Protein(s)

NM_001353143.1 → NP_001340072.1 thioredoxin reductase 2, mitochondrial isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame coding exon in the 3' region compared to variant 1. The resulting shorter isoform (2) is missing an internal protein segment compared to isoform 1.

Source sequence(s)

AB027566, AF412308, BF465261

Consensus CDS

CCDS88895.1

UniProtKB/TrEMBL

A0A0U1RPV8

Related

ENSMUSP00000146143.3, ENSMUST00000206606.3

Conserved Domains (1) summary

cl27343
Location:43 → 496

Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain
NM_013711.3 → NP_038739.2 thioredoxin reductase 2, mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_038739.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the predominant transcript and encodes the longer isoform (1).

Source sequence(s)

AB027566, BF465261

Consensus CDS

CCDS79434.1

UniProtKB/TrEMBL

A0A0M3HEQ0

Related

ENSMUSP00000111269.4, ENSMUST00000115606.9

Conserved Domains (4) summary

TIGR01438
Location:43 → 527

TGR; thioredoxin and glutathione reductase selenoprotein

pfam00070
Location:223 → 289

Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase

pfam02852
Location:399 → 508

Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerization domain

cl21454
Location:43 → 70

NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins