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TXNRD3 thioredoxin reductase 3 [ Homo sapiens (human) ]

Gene ID: 114112, updated on 14-Nov-2024

Summary

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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

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See TXNRD3 in Genome Data Viewer
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_000003.12Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:126248434-126249422 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20439 Neighboring gene carbohydrate sulfotransferase 13 Neighboring gene chromosome 3 open reading frame 22 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:126258788-126258962 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr3:126267915-126268796 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:126268797-126269679 Neighboring gene uncharacterized LOC105374090 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:126288341-126289251 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:126289252-126290161 Neighboring gene RNA, 5S ribosomal pseudogene 138 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:126329686-126329869 Neighboring gene METTL5 pseudogene 2 Neighboring gene Sharpr-MPRA regulatory region 1093 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14679 Neighboring gene nucleoporin 210 pseudogene 1 Neighboring gene SF3A2 pseudogene 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues 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?
  1. [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].
  2. 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.
  3. 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.
  4. 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.
  5. 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.
Submit: New GeneRIF Correction

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)

Pathways from PubChem

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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

Homology

Clone Names

  • MGC163418, MGC163420

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
NP_443115.1

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)

  1. 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

  2. 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
    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

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    126607050..126655124 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    129339825..129387575 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. 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.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q6F5E7.1 GenPept UniProtKB/Swiss-Prot:Q6F5E7
Q86VQ6.4 GenPept UniProtKB/Swiss-Prot:Q86VQ6

Gene LinkOut

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