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    TXNRD1 thioredoxin reductase 1 [ Homo sapiens (human) ]

    Gene ID: 7296, updated on 28-Oct-2024

    Summary

    Official Symbol
    TXNRD1provided by HGNC
    Official Full Name
    thioredoxin reductase 1provided by HGNC
    Primary source
    HGNC:HGNC:12437
    See related
    Ensembl:ENSG00000198431 MIM:601112; AllianceGenome:HGNC:12437
    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; TR1; TXNR; TRXR1; TXNR1; GRIM-12
    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 an ubiquitously expressed, cytosolic form of TrxR, which 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. Alternative splicing, primarily at the 5' end, results in transcript variants encoding same or different isoforms, including a glutaredoxin-containing isoform that is predominantly expressed in testis. [provided by RefSeq, May 2017]
    Expression
    Ubiquitous expression in adrenal (RPKM 41.8), gall bladder (RPKM 31.2) and 24 other tissues See more
    Orthologs
    NEW
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    Try the new Transcript table

    Genomic context

    See TXNRD1 in Genome Data Viewer
    Location:
    12q23.3
    Exon count:
    18
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (104215779..104350307)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (104177472..104311962)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (104609557..104744085)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105369947 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23741 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23744 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23747 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23754 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23756 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23757 Neighboring gene long intergenic non-protein coding RNA 2385 Neighboring gene Sharpr-MPRA regulatory region 15351 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23771 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:104609333-104609949 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:104609950-104610565 Neighboring gene NFE2L2 motif-containing MPRA enhancer 194 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23775 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23777 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:104628245-104628471 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23786 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23788 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23792 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23801 Neighboring gene uncharacterized LOC124903002 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23817 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:104665873-104667072 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23822 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23828 Neighboring gene ribosomal protein L18a pseudogene 3 Neighboring gene Sharpr-MPRA regulatory region 5029 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr12:104680011-104681210 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:104681597-104682144 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:104682145-104682690 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23836 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23840 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:104697445-104698317 Neighboring gene EP300 interacting inhibitor of differentiation 3 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23854 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:104736854-104737098 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_23864 Neighboring gene Sharpr-MPRA regulatory region 7710 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:104761070-104761775 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:104765060-104765816 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:104765817-104766574 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:104766575-104767330 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:104768893-104769404 Neighboring gene uncharacterized LOC105369949 Neighboring gene MPRA-validated peak1927 silencer Neighboring gene uncharacterized LOC124903003

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    HIV-1 assembly incorporates TXN (Trx1) and TXNRD1 (TrxR1) into viral particles PubMed
    HIV-1 IIIB requires thioredoxin reductase-1 (TrxR1) for virus entry; inhibition was shown through organotellurium inhibitor use PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 Env (gp120) requires thioredoxin-1 (Trx1); Env disulfide bonds are reduced by thioredoxin resulting in virus entry PubMed
    Tat tat Thioredoxin reductase-1 (TR1), a selenium-containing pyridine nucleotide-disulfide oxidoreductase, acts as a negative regulator of Tat-dependent transcription in a NF-kappaB-independent pathway PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • MGC9145

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables FAD binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables NADPH peroxidase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables identical protein binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables thioredoxin-disulfide reductase (NADPH) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables thioredoxin-disulfide reductase (NADPH) activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in cell population proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cell redox homeostasis IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in cellular oxidant detoxification IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in mesoderm formation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in signal transduction NAS
    Non-traceable Author Statement
    more info
    PubMed 
    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 TAS
    Traceable Author Statement
    more info
     
    located_in extracellular exosome HDA PubMed 
    located_in fibrillar center IDA
    Inferred from Direct Assay
    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

    Preferred Names
    thioredoxin reductase 1, cytoplasmic
    Names
    KM-102-derived reductase-like factor
    gene associated with retinoic and IFN-induced mortality 12 protein
    gene associated with retinoic and interferon-induced mortality 12 protein
    oxidoreductase
    peroxidase TXNRD1
    selenoprotein TXNRD1
    testis tissue sperm-binding protein Li 46a
    thioredoxin reductase GRIM-12
    thioredoxin reductase TR1
    NP_001087240.1
    NP_001248374.1
    NP_001248375.1
    NP_003321.3
    NP_877393.1
    NP_877419.1
    NP_877420.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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

    1. NG_029392.1 RefSeqGene

      Range
      4999..139527
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001093771.3NP_001087240.1  thioredoxin reductase 1, cytoplasmic isoform 5

      See identical proteins and their annotated locations for NP_001087240.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7, also known as beta 1) represents use of an alternate upstream promoter, and contains additional exons at the 5' end compared to variant 1. The encoded isoform (5, also known as TXNRD1_v3 or v3) has a longer and distinct N-terminus, resulting from translation initiation at an in-frame upstream start codon, compared to isoform 1. It is predominantly expressed in Leydig cells of testis, and contains an atypical N-terminal glutaredoxin domain, which induces actin and tubulin polymerization, leading to formation of cell membrane protrusions (PMID:18042542).
      Source sequence(s)
      AI097548, AK226071, AY057105, BC018122, DC418649
      Consensus CDS
      CCDS53820.1
      UniProtKB/Swiss-Prot
      B7Z1F4, B7Z3Y8, B7Z904, E9PMY9, F5H780, Q16881, Q6FI31, Q6VB40, Q6VB41, Q6VB42, Q6VBP2, Q6VBP3, Q6VBP4, Q6VBP5, Q6VBP9, Q6VBQ0, Q6YNQ1, Q76P53, Q7LA96, Q8WVC8, Q99475, Q9UES8, Q9UH79
      UniProtKB/TrEMBL
      A0A140VKC9
      Related
      ENSP00000434516.1, ENST00000525566.6
      Conserved Domains (4) summary
      cd03419
      Location:68148
      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:161649
      TGR; thioredoxin and glutathione reductase selenoprotein
      pfam00070
      Location:342418
      Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase
      pfam02852
      Location:521631
      Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerization domain
    2. NM_001261445.2NP_001248374.1  thioredoxin reductase 1, cytoplasmic isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) uses an alternate donor splice site at the 5' terminal exon, which results in translation initiation from an in-frame upstream start codon compared to variant 1. The encoded isoform (3) has a longer and distinct N-terminus compared to isoform 1.
      Source sequence(s)
      AI097548, AK226071, AK295067, BC018122, DA440625, DC351122, DC400503
      UniProtKB/TrEMBL
      B7Z2S5
      Conserved Domains (4) summary
      TIGR01438
      Location:61549
      TGR; thioredoxin and glutathione reductase selenoprotein
      pfam00070
      Location:242318
      Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase
      pfam02852
      Location:421531
      Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerization domain
      cl00388
      Location:148
      Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold
    3. NM_001261446.2NP_001248375.1  thioredoxin reductase 1, cytoplasmic isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) lacks an internal exon in the 5' region, which results in translation initiation from an in-frame downstream start codon compared to variant 1. The encoded isoform (4) has a shorter N-terminus compared to isoform 1.
      Source sequence(s)
      AI097548, AK226071, AK293322, BC018122
      Consensus CDS
      CCDS58274.1
      UniProtKB/TrEMBL
      B2R5P6
      Related
      ENSP00000434919.1, ENST00000529546.5
      Conserved Domains (3) summary
      TIGR01438
      Location:1461
      TGR; thioredoxin and glutathione reductase selenoprotein
      pfam00070
      Location:154230
      Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase
      pfam02852
      Location:333443
      Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerization domain
    4. NM_003330.4NP_003321.3  thioredoxin reductase 1, cytoplasmic isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) uses an alternate donor splice site at the 5' terminal exon, which results in translation initiation from an in-frame upstream start codon compared to variant 1. The encoded isoform (2, also known as TXNRD1_v2) has a longer and distinct N-terminus, and is thought to differentially regulate genes associated with differentiation and adhesion compared to isoform 1 (PMID:26464515).
      Source sequence(s)
      AI097548, AK226071, BC018122, DC351122
      Consensus CDS
      CCDS53821.1
      UniProtKB/TrEMBL
      B7Z2S5
      Related
      ENSP00000435929.1, ENST00000526691.5
      Conserved Domains (4) summary
      TIGR01438
      Location:63551
      TGR; thioredoxin and glutathione reductase selenoprotein
      pfam00070
      Location:244320
      Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase
      pfam02852
      Location:423533
      Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerization domain
      cl00388
      Location:450
      Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold
    5. NM_182729.3NP_877393.1  thioredoxin reductase 1, cytoplasmic isoform 1

      See identical proteins and their annotated locations for NP_877393.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the predominant transcript and encodes isoform 1 (also known as TXNRD1_v1). This isoform is thought to regulate expression of genes associated with differentiation and adhesion (PMID:26464515). Variants 1-3 encode the same isoform.
      Source sequence(s)
      AI097548, AK226071, BC018122, DC400503
      Consensus CDS
      CCDS53823.1
      UniProtKB/TrEMBL
      B2R5P6
      Related
      ENSP00000421934.2, ENST00000503506.6
      Conserved Domains (3) summary
      TIGR01438
      Location:11499
      TGR; thioredoxin and glutathione reductase selenoprotein
      pfam00070
      Location:192268
      Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase
      pfam02852
      Location:371481
      Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerization domain
    6. NM_182742.3NP_877419.1  thioredoxin reductase 1, cytoplasmic isoform 1

      See identical proteins and their annotated locations for NP_877419.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1-3 encode the same isoform (1, also known as TXNRD1_v1), which is thought to regulate expression of genes associated with differentiation and adhesion (PMID:26464515).
      Source sequence(s)
      AI097548, AK226071, BC018122, DA238692
      Consensus CDS
      CCDS53823.1
      UniProtKB/TrEMBL
      B2R5P6
      Conserved Domains (3) summary
      TIGR01438
      Location:11499
      TGR; thioredoxin and glutathione reductase selenoprotein
      pfam00070
      Location:192268
      Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase
      pfam02852
      Location:371481
      Pyr_redox_dim; Pyridine nucleotide-disulphide oxidoreductase, dimerization domain
    7. NM_182743.3NP_877420.1  thioredoxin reductase 1, cytoplasmic isoform 1

      See identical proteins and their annotated locations for NP_877420.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks a 5' non-coding exon; therefore, has a shorter 5' UTR compared to variant 1. Variants 1-3 encode the same isoform (1, also known as TXNRD1_v1), which is thought to regulate expression of genes associated with differentiation and adhesion (PMID:26464515).
      Source sequence(s)
      AI097548, AK226071, BC018122, DA319870
      Consensus CDS
      CCDS53823.1
      UniProtKB/TrEMBL
      B2R5P6
      Conserved Domains (3) summary
      TIGR01438
      Location:11499
      TGR; thioredoxin and glutathione reductase selenoprotein
      pfam00070
      Location:192268
      Pyr_redox; Pyridine nucleotide-disulphide oxidoreductase
      pfam02852
      Location:371481
      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_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      104215779..104350307
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      104177472..104311962
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)