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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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    Related articles in PubMed

    1. [Effect of Selenoprotein Thioredoxin Reductase 3 on the Survival Prognosis of Tumor Patients]. He AY, et al. Zhongguo Yi Xue Ke Xue Yuan Xue Bao, 2022 Dec. PMID 36621786
    2. Identification and characterization of novel variants of the thioredoxin reductase 3 new transcript 1 TXNRD3NT1. Matsuzaka Y, et al. Mamm Genome, 2005 Jan. PMID 15674732
    3. Kinetic characterization of wild-type and mutant human thioredoxin glutathione reductase defines its reaction and regulatory mechanisms. Brandstaedter C, et al. FEBS J, 2018 Feb. PMID 29222842
    4. Identification, expression analysis and polymorphism of a novel RLTPR gene encoding a RGD motif, tropomodulin domain and proline/leucine-rich regions. Matsuzaka Y, et al. Gene, 2004 Dec 22. PMID 15588584
    5. The selenoproteins GPx2, TrxR2 and TrxR3 are regulated by Wnt signalling in the intestinal epithelium. Kipp AP, et al. Biochim Biophys Acta, 2012 Oct. PMID 22683372

    See all (22) citations in PubMed

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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