TXNRD3 thioredoxin reductase 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TXNRD3provided by HGNC
Official Full Name: thioredoxin reductase 3provided by HGNC
Primary source: HGNC:HGNC:20667
See related: Ensembl:ENSG00000197763 MIM:606235; AllianceGenome:HGNC:20667
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: TGR; TR2; TRXR3; TXNR3; TR2IT1; TXNRD3NB; TXNRD3IT1; TXNRD3NT1
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 the third TrxR, which unlike the other two isozymes, contains an additional N-terminal glutaredoxin (Grx) domain, and shows highest expression in testis. The Grx domain allows this isozyme to participate in both Trx and glutathione systems. 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 have been found for this gene. Experimental evidence suggests the use of a non-AUG (CUG) codon as a translation initiation codon (PMID:20018845). [provided by RefSeq, Aug 2017]
Expression: Broad expression in testis (RPKM 13.6), thyroid (RPKM 4.0) and 21 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3q21.3

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (126607050..126655124, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (129339825..129387575, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (126325893..126373967, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

[Effect of Selenoprotein Thioredoxin Reductase 3 on the Survival Prognosis of Tumor Patients].
Title: [Effect of Selenoprotein Thioredoxin Reductase 3 on the Survival Prognosis of Tumor Patients].
Findings represent the first characterization of hTGR and provide new insights into the reaction mechanism and the regulation of monothiol Grx-containing thioredoxin glutathione reductases.
Title: Kinetic characterization of wild-type and mutant human thioredoxin glutathione reductase defines its reaction and regulatory mechanisms.
A role of GPx2, TrxR2 and TrxR3 in proliferation, apoptosis and, therefore, also during cancer development.
Title: The selenoproteins GPx2, TrxR2 and TrxR3 are regulated by Wnt signalling in the intestinal epithelium.
This study pertains to use of non-AUG (CUG) start codon in mouse thioredoxin reductase 3 gene, and conservation of this site in other mammals.
Title: CUG start codon generates thioredoxin/glutathione reductase isoforms in mouse testes.
Observational study of gene-disease association. (HuGE Navigator)
Title: A genetic association analysis of cognitive ability and cognitive ageing using 325 markers for 109 genes associated with oxidative stress or cognition.

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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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

TXNRD3_3256 (e-PCR)
- UniSTS:462605

STS-N36130 (e-PCR)
- UniSTS:58974

G31568 (e-PCR)
- UniSTS:70311

SHGC-77314 (e-PCR)
- UniSTS:4321

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables flavin adenine dinucleotide 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	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in cell redox homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell redox homeostasis	NAS Non-traceable Author Statement more info	PubMed
involved_in cellular oxidant detoxification	IEA Inferred from Electronic Annotation more info
involved_in spermatogenesis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
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 endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: thioredoxin reductase 3

Names: TXNRD3 neighbor gene protein; selenoprotein TXNRD3; thioredoxin and glutathione reductase; thioredoxin glutathione reductase; thioredoxin reductase 2 intronic transcript 1; thioredoxin reductase 3 intronic transcript 1; thioredoxin reductase 3 neighbor gene protein; thioredoxin reductase 3 new transcript 1; thioredoxin reductase TR2

NP_001166984.1

EC 1.8.1.9

NP_443115.1

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_001173513.3 → NP_001166984.1 thioredoxin reductase 3 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame coding exon compared to variant 1, which results in a shorter isoform (2) missing an internal protein segment compared to isoform 1. A non-AUG (CUG) codon is used as translation initiation codon.

Source sequence(s)

AC024558

Consensus CDS

CCDS77810.1

UniProtKB/TrEMBL

H0YBI6

Related

ENSP00000429584.3, ENST00000523403.3

Conserved Domains (4) summary

cd03419
Location:67 → 148

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, ...

TIGR01438
Location:155 → 607

TGR; thioredoxin and glutathione reductase selenoprotein

pfam00070
Location:336 → 412

Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase

pfam02852
Location:508 → 589

Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerization domain
NM_052883.3 → NP_443115.1 thioredoxin reductase 3 isoform 1

See identical proteins and their annotated locations for NP_443115.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the predominant transcript, and encodes the longer isoform (1). A non-AUG (CUG) codon is used as translation initiation codon.

Source sequence(s)

AC024558

Consensus CDS

CCDS77811.1

UniProtKB/Swiss-Prot

Q6F5E7, Q6PIS8, Q86VQ6, Q9NNW6, Q9P101

UniProtKB/TrEMBL

H0YBQ0

Related

ENSP00000430031.4, ENST00000524230.9

Conserved Domains (4) summary

cd03419
Location:67 → 148

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, ...

TIGR01438
Location:155 → 643

TGR; thioredoxin and glutathione reductase selenoprotein

pfam00070
Location:336 → 412

Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase

pfam02852
Location:515 → 625

Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerization domain

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_000003.12 Reference GRCh38.p14 Primary Assembly

Range

126607050..126655124 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

129339825..129387575 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001039783.1: Suppressed sequence

Description

NM_001039783.1: This RefSeq was removed because currently there is support for the transcript but not for the protein.