TXNRD2 thioredoxin reductase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TXNRD2provided by HGNC
Official Full Name: thioredoxin reductase 2provided by HGNC
Primary source: HGNC:HGNC:18155
See related: Ensembl:ENSG00000184470 MIM:606448; AllianceGenome:HGNC:18155
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: TR; TR3; SELZ; GCCD5; TRXR2; TXNR2; TR-BETA
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, including a few localized in the cytosol and some lacking the C-terminal Sec residue, have been found for this gene. [provided by RefSeq, Jun 2017]
Expression: Ubiquitous expression in adrenal (RPKM 8.7), prostate (RPKM 8.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 22q11.21

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (19875522..19941818, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (20252392..20319509, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (19863045..19929341, complement)

Chromosome 22 - NC_000022.11 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

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Insight into the role of TXNRD2 in steroidogenesis through a novel homozygous TXNRD2 splice variant.
Title: Insight into the role of TXNRD2 in steroidogenesis through a novel homozygous TXNRD2 splice variant.
Association analysis of variants rs35934224 in TXNRD2 and rs6478746 in LMX1B in primary angle-closure and pseudoexfoliation glaucoma.
Title: Association analysis of variants rs35934224 in TXNRD2 and rs6478746 in LMX1B in primary angle-closure and pseudoexfoliation glaucoma.
TXNRD2 (rs35934224) CT genotype and primary open-angle glaucoma: correspondenceReply to ""TXNRD2 (rs35934224) CT genotype and primary open-angle glaucoma: correspondence""Primary open-angle glaucomaGenome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucomaGenome-wide association study of primary open-angle glaucoma in continental and admixed African popula...
Title: TXNRD2 (rs35934224) CT genotype and primary open-angle glaucoma: correspondenceReply to "TXNRD2 (rs35934224) CT genotype and primary open-angle glaucoma: correspondence"Primary open-angle glaucomaGenome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucomaGenome-wide association study of primary open-angle glaucoma in continental and admixed African populations.
TXNRD2 (rs35934224) CT genotype as possible protective marker for primary open-angle glaucoma in a Brazilian population.
Title: TXNRD2 (rs35934224) CT genotype as possible protective marker for primary open-angle glaucoma in a Brazilian population.
miR-195-5p exerts tumor-suppressive functions in human lung cancer cells through targeting TrxR2.
Title: miR-195-5p exerts tumor-suppressive functions in human lung cancer cells through targeting TrxR2.
The aim of the study was to investigate the association between rs5859 in Sep15, rs1139793 in TrxR2 polymorphisms with the risks of KBD and to detect the expression of AP-1 pathway.
Title: The study on polymorphisms of Sep15 and TrxR2 and the expression of AP-1 signaling pathway in Kashin-Beck disease.
Based on recent research, it has been reported that the modulation of the Trx/TrxR system may be considered as a new target in the management of the metabolic syndrome, insulin resistance, and type 2 diabetes, as well as in the treatment of hypertension and atherosclerosis. In this review evidence about a possible role of this system as a marker of the metabolic syndrome is reported. [review]
Title: The role of the thioredoxin/thioredoxin reductase system in the metabolic syndrome: towards a possible prognostic marker?
TrxR2 was overexpressed in non-small-cell lung cancer cells; our results suggest that TrxR2 acts as an oncogenic gene in the context of lung cancer progression
Title: Inhibition of TrxR2 suppressed NSCLC cell proliferation, metabolism and induced cell apoptosis through decreasing antioxidant activity.
p53R2 acts as a positive regulator of TrxR2 activity in mitochondria both under normal physiological conditions and during the cellular response to DNA damage
Title: p53R2 regulates thioredoxin reductase activity through interaction with TrxR2.
TrxR2 deficiency-induced impaired proliferation and death of chondrocytes may be the pathological mechanism of the osteoarthropathy due to Selenium deficiency.
Title: TrxR2 deficiencies promote chondrogenic differentiation and induce apoptosis of chondrocytes through mitochondrial reactive oxygen species.

Submit: New GeneRIF Correction See all GeneRIFs (34)

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

Associated conditions

Description	Tests
Glucocorticoid deficiency 5 MedGen: C4540522 OMIM: 617825 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome wide association study of SNP-, gene-, and pathway-based approaches to identify genes influencing susceptibility to Staphylococcus aureus infections. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma. EBI GWAS Catalog EBI GWAS CatalogPubMed

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
matrix	gag	HIV-1 MA upregulates TXNRD2 (TR3) gene expression in HepG2 cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D8S2279 (e-PCR)
- UniSTS:473907

RH47909 (e-PCR)
- UniSTS:70206

TXNRD2_1117 (e-PCR)
- UniSTS:277850

RH80249 (e-PCR)
- UniSTS:91599

SHGC-58266 (e-PCR)
- UniSTS:980

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables flavin adenine dinucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein-containing complex binding	IEA Inferred from Electronic Annotation more info
enables thioredoxin-disulfide reductase (NADPH) activity	IBA Inferred from Biological aspect of Ancestor more info
enables thioredoxin-disulfide reductase (NADPH) activity	ISS Inferred from Sequence or Structural Similarity 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	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular oxidant detoxification	IEA Inferred from Electronic Annotation more info
involved_in response to hyperoxia	IEA Inferred from Electronic Annotation more info
involved_in response to oxygen radical	TAS Traceable Author Statement more info	PubMed
involved_in response to selenium ion	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in axon	IEA Inferred from Electronic Annotation 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	IDA Inferred from Direct Assay more info
located_in dendrite	IEA Inferred from Electronic Annotation more info
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
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

General protein information

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Preferred Names: thioredoxin reductase 2, mitochondrial

Names: selenoprotein Z; thioredoxin reductase 3; thioredoxin reductase TR3; thioredoxin reductase beta

NP_001269441.1

EC 1.8.1.9

NP_001339229.1

EC 1.8.1.9

NP_001339230.1

EC 1.8.1.9

NP_001339231.1

EC 1.8.1.9

NP_001339232.1

EC 1.8.1.9

NP_006431.2

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.

Genomic

NG_011835.1 RefSeqGene

Range

4845..71320

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_417

mRNA and Protein(s)

NM_001282512.3 → NP_001269441.1 thioredoxin reductase 2, mitochondrial isoform 5 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks several exons in the 3' coding region, and contains an alternate 3' terminal exon compared to variant 1. The resulting isoform (5) is shorter, with a distinct C-terminus (lacking selenocysteine) compared to isoform 1.

Source sequence(s)

AC000078, AF044212, AF106697, BM678200, BX109590, CD742908

Consensus CDS

CCDS63402.1

UniProtKB/TrEMBL

E7EWK1, Q6M1B7

Related

ENSP00000334451.9, ENST00000334363.14

Conserved Domains (2) summary

pfam00070
Location:220 → 295

Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase

cl14785
Location:124 → 190

FMT_C_like; Carboxy-terminal domain of Formyltransferase and similar domains
NM_001352300.2 → NP_001339229.1 thioredoxin reductase 2, mitochondrial isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2, also known as TrxR2A) uses an alternate in-frame acceptor splice site at an internal coding exon, and contains an unspliced 3' UTR compared to variant 1. The resulting isoform (2) is 1 aa shorter than isoform 1. It is localized to the mitochondria, and its overexpression results in increased apoptosis (PMID:16298692).

Source sequence(s)

AF044212, AF106697, AF166126, AF201385

Consensus CDS

CCDS87001.1

UniProtKB/TrEMBL

A0A182DWF3

Related

ENSP00000383363.1, ENST00000400519.6

Conserved Domains (1) summary

cl27343
Location:38 → 523

Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain
NM_001352301.2 → NP_001339230.1 thioredoxin reductase 2, mitochondrial isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate 5' terminal exon, and uses an alternate in-frame translation initiation codon compared to variant 1. The resulting isoform (3) has a distinct and shorter N-terminus lacking the N-terminal mitochondrial targeting signal, compared to isoform 1, so it is likely localized in the cytosol.

Source sequence(s)

AB019695, AF044212, AF166126

Consensus CDS

CCDS86999.1

UniProtKB/TrEMBL

A0A182DWF2

Related

ENSP00000383362.1, ENST00000400518.5

Conserved Domains (1) summary

cl27343
Location:9 → 494

Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain
NM_001352302.2 → NP_001339231.1 thioredoxin reductase 2, mitochondrial isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains an alternate 5' terminal exon, which results in translation initiation from an in-frame downstream start codon compared to variant 1. The encoded isoform (4, also known as hTR3c) has a shorter N-terminus compared to isoform 1. It is localized in the cytosol (PMID:16774913).

Source sequence(s)

AF044212, AF166126, AF166127

Consensus CDS

CCDS86998.1

UniProtKB/TrEMBL

A0A182DWF2

Related

ENSP00000485128.2, ENST00000542719.6

Conserved Domains (1) summary

cl27343
Location:1 → 428

Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain
NM_001352303.2 → NP_001339232.1 thioredoxin reductase 2, mitochondrial isoform 6

Status: REVIEWED

Description

Transcript Variant: This variant (6) contains alternate 5' and 3' terminal exons compared to variant 1. The resulting shorter isoform (6, also known as hTR3b) has distinct N- and C- termini compared to isoform 1, and lacks selenocysteine. It is localized in the cytosol (PMID:16774913).

Source sequence(s)

AC000078, AC000090, AF044212, BM678200, BX109590, BX957216, CD742908

Consensus CDS

CCDS87000.1

UniProtKB/TrEMBL

A0A096LPD9, Q6M1B7

Related

ENSP00000485543.1, ENST00000491939.6

Conserved Domains (1) summary

cl27343
Location:7 → 288

Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain
NM_006440.5 → NP_006431.2 thioredoxin reductase 2, mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_006431.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the predominant transcript and encodes the longest isoform (1, also known as hTR3a). This isoform is localized to the mitochondria (PMID:16774913).

Source sequence(s)

AF044212, AF106697, R46611

Consensus CDS

CCDS42981.1

UniProtKB/Swiss-Prot

O95840, Q96IJ2, Q9H2Z5, Q9NNW7, Q9NZV3, Q9NZV4, Q9P2Y0, Q9P2Y1, Q9UQU8

UniProtKB/TrEMBL

A0A182DWF3

Related

ENSP00000383365.1, ENST00000400521.7

Conserved Domains (4) summary

TIGR01438
Location:39 → 524

TGR; thioredoxin and glutathione reductase selenoprotein

pfam00070
Location:220 → 295

Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase

pfam02852
Location:396 → 505

Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerization domain

cl14785
Location:124 → 190

FMT_C_like; Carboxy-terminal domain of Formyltransferase and similar domains

RNA

NR_147957.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (7) uses an alternate acceptor splice site at the penultimate exon compared to variant 1. It is represented as non-coding because the use of the 5'-most translation start codon, as used in variant 1, renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AF044212, AF106697, AF166126, AK097708

Related

ENST00000474308.5

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000022.11 Reference GRCh38.p14 Primary Assembly

Range

19875522..19941818 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060946.1 Alternate T2T-CHM13v2.0

Range

20252392..20319509 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_145747.1: Suppressed sequence

Description

NM_145747.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
NM_145748.1: Suppressed sequence

Description

NM_145748.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.