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TXNRD1 thioredoxin reductase 1 [ Homo sapiens (human) ]

Gene ID: 7296, updated on 21-Apr-2019

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
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; 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

Genomic context

See TXNRD1 in Genome Data Viewer
Location:
12q23.3
Exon count:
18
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 12 NC_000012.12 (104215779..104350307)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (104609537..104744085)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105369947 Neighboring gene long intergenic non-protein coding RNA 2385 Neighboring gene NFE2L2 motif-containing MPRA enhancer 194 Neighboring gene ribosomal protein L18a pseudogene 3 Neighboring gene EP300 interacting inhibitor of differentiation 3 Neighboring gene uncharacterized LOC105369949 Neighboring gene carbohydrate sulfotransferase 11 Neighboring gene ATP synthase F(0) complex subunit C1, mitochondrial pseudogene

Genomic regions, transcripts, and products

Expression

  • Project title: 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 FunctionsWhat'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 BioSystems

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC9145

Gene Ontology Provided by GOA

Function Evidence Code Pubs
electron transfer activity IEA
Inferred from Electronic Annotation
more info
 
flavin adenine dinucleotide binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein disulfide oxidoreductase activity IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
cell proliferation IEA
Inferred from Electronic Annotation
more info
 
cellular oxidant detoxification IEA
Inferred from Electronic Annotation
more info
 
cellular response to oxidative stress TAS
Traceable Author Statement
more info
 
electron transport chain IEA
Inferred from Electronic Annotation
more info
 
mesoderm formation IEA
Inferred from Electronic Annotation
more info
 
nucleobase-containing small molecule interconversion TAS
Traceable Author Statement
more info
 
regulation of lipid metabolic process TAS
Traceable Author Statement
more info
 
selenium compound metabolic process TAS
Traceable Author Statement
more info
 
signal transduction NAS
Non-traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
cytosol TAS
Traceable Author Statement
more info
 
extracellular exosome HDA PubMed 
fibrillar center IDA
Inferred from Direct Assay
more info
 
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
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)

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
    Q16881
    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_001261445.1NP_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, DC401138
    UniProtKB/Swiss-Prot
    Q16881
    UniProtKB/TrEMBL
    B7Z2S5
    Related
    ENSP00000373506.4, ENST00000388854.7
    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_001261446.1NP_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, DC400503, DC401138
    Consensus CDS
    CCDS58274.1
    UniProtKB/Swiss-Prot
    Q16881
    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_003330.3NP_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, DC400503, DC401138
    Consensus CDS
    CCDS53821.1
    UniProtKB/Swiss-Prot
    Q16881
    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_182729.2NP_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, DC401138
    Consensus CDS
    CCDS53823.1
    UniProtKB/Swiss-Prot
    Q16881
    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_182742.2NP_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, DC400503, DC401138
    Consensus CDS
    CCDS53823.1
    UniProtKB/Swiss-Prot
    Q16881
    Related
    ENSP00000347020.7, ENST00000354940.10
    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_182743.2NP_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, DC400503, DC401138
    Consensus CDS
    CCDS53823.1
    UniProtKB/Swiss-Prot
    Q16881
    Related
    ENSP00000432812.1, ENST00000526950.1
    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: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p12 Primary Assembly

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