U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from GEO Profiles

    • Showing Current items.

    TXNDC5 thioredoxin domain containing 5 [ Homo sapiens (human) ]

    Gene ID: 81567, updated on 10-Dec-2024

    Summary

    Go to the top of the page Help
    Official Symbol
    TXNDC5provided by HGNC
    Official Full Name
    thioredoxin domain containing 5provided by HGNC
    Primary source
    HGNC:HGNC:21073
    See related
    Ensembl:ENSG00000239264 MIM:616412; AllianceGenome:HGNC:21073
    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
    HCC2; ERP46; HCC-2; STRF8; PDIA15; UNQ364; ENDOPDI
    Summary
    This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal endoplasmic reticulum (ER)-signal sequence, three catalytically active thioredoxin domains and a C-terminal ER-retention sequence. Its expression is induced by hypoxia and its role may be to protect hypoxic cells from apoptosis. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring upstream BLOC1S5 gene. [provided by RefSeq, Dec 2016]
    Expression
    Ubiquitous expression in urinary bladder (RPKM 151.7), colon (RPKM 127.4) and 25 other tissues See more
    Orthologs
    mouse all
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Go to the top of the page Help
    See TXNDC5 in Genome Data Viewer
    Location:
    6p24.3
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (7881517..7910788, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (7750266..7779537, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (7881750..7911021, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene MPRA-validated peak5647 silencer Neighboring gene ribosomal protein L29 pseudogene 1 Neighboring gene uncharacterized LOC105374906 Neighboring gene NANOG hESC enhancer GRCh37_chr6:7685011-7685581 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:7696296-7696460 Neighboring gene Sharpr-MPRA regulatory region 4297 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23951 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:7734858-7735358 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:7735359-7735859 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr6:7763783-7764982 Neighboring gene bone morphogenetic protein 6 Neighboring gene BLOC1S5-TXNDC5 readthrough (NMD candidate) Neighboring gene MED14-independent group 3 enhancer GRCh37_chr6:7882299-7883498 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16891 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16893 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16892 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23952 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr6:7919793-7920992 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23953 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23954 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16894 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:7986177-7986678 Neighboring gene EEF1E1-BLOC1S5 readthrough (NMD candidate) Neighboring gene phosphatidylinositol-4-phosphate 5-kinase type 1 pseudogene 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:8012284-8012492 Neighboring gene MPRA-validated peak5648 silencer Neighboring gene biogenesis of lysosomal organelles complex 1 subunit 5 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:8063830-8064456

    Genomic regions, transcripts, and products

    Go to the top of the page Help

    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

    Go to the top of the pageHelp

    Related articles in PubMed

    1. Maternal serum TXNDC5 levels and thiol/disulfide homeostasis in preeclamptic pregnancies. Kaya B, et al. J Matern Fetal Neonatal Med, 2020 Feb. PMID 30522366
    2. The novel role of ER protein TXNDC5 in the pathogenesis of organ fibrosis: mechanistic insights and therapeutic implications. Hung CT, et al. J Biomed Sci, 2022 Sep 2. PMID 36050716, Free PMC Article
    3. The role and mechanism of TXNDC5 in diseases. Wang X, et al. Eur J Med Res, 2022 Aug 8. PMID 35934705, Free PMC Article
    4. Hcc-2, a novel mammalian ER thioredoxin that is differentially expressed in hepatocellular carcinoma. Nissom PM, et al. FEBS Lett, 2006 Apr 17. PMID 16574106
    5. Association of TXNDC5 gene polymorphisms and susceptibility to nonsegmental vitiligo in the Korean population. Jeong KH, et al. Br J Dermatol, 2010 Apr. PMID 19906073

    See all (152) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The role and mechanism of TXNDC5 in disease progression.
      Title: The role and mechanism of TXNDC5 in disease progression.
    2. Hepatitis E virus ORF3 protein hijacking thioredoxin domain-containing protein 5 (TXNDC5) for its stability to promote viral particle release.
      Title: Hepatitis E virus ORF3 protein hijacking thioredoxin domain-containing protein 5 (TXNDC5) for its stability to promote viral particle release.
    3. Identification of thioredoxin domain containing family members' expression pattern and prognostic value in diffuse gliomas via in silico analysis.
      Title: Identification of thioredoxin domain containing family members' expression pattern and prognostic value in diffuse gliomas via in silico analysis.
    4. The novel role of ER protein TXNDC5 in the pathogenesis of organ fibrosis: mechanistic insights and therapeutic implications.
      Title: The novel role of ER protein TXNDC5 in the pathogenesis of organ fibrosis: mechanistic insights and therapeutic implications.
    5. The role and mechanism of TXNDC5 in diseases.
      Title: The role and mechanism of TXNDC5 in diseases.
    6. Circ_0078710 promotes the development of liver cancer by upregulating TXNDC5 via miR-431-5p.
      Title: Circ_0078710 promotes the development of liver cancer by upregulating TXNDC5 via miR-431-5p.
    7. Fibroblast-enriched endoplasmic reticulum protein TXNDC5 promotes pulmonary fibrosis by augmenting TGFbeta signaling through TGFBR1 stabilization.
      Title: Fibroblast-enriched endoplasmic reticulum protein TXNDC5 promotes pulmonary fibrosis by augmenting TGFβ signaling through TGFBR1 stabilization.
    8. serum levels were elevated in both early-onset and late-onset pre-eclampsia
      Title: Maternal serum TXNDC5 levels and thiol/disulfide homeostasis in preeclamptic pregnancies.
    9. HERG1 contributes to poor prognosis in patients with esophageal squamous cell carcinoma (ESCC) by promoting ESCC cell proliferation, migration, and invasion via TXNDC5 through the PI3K/AKT signaling pathway. Our findings provided novel insights into the pathology of ESCC and role of HERG1 in tumor progression, suggesting that targeting HERG1 has potential diagnostic and therapeutic value for ESCC treatment.
      Title: HERG1 promotes esophageal squamous cell carcinoma growth and metastasis through TXNDC5 by activating the PI3K/AKT pathway.
    10. These results strongly suggest that high levels of TXNDC5 in Rheumatoid Arthritis synovial tissues suppress CXCL10 and TNFSF10 expression.
      Title: CXCL10 and TRAIL Are Upregulated by TXNDC5 in Rheumatoid Arthritis Fibroblast-like Synoviocytes.
    Submit: New GeneRIF Correction See all GeneRIFs (37)

    Phenotypes

    Go to the top of the page Help

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

    Go to the top of the page Help

    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

    Go to the top of the page Help

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 is identified to have a physical interaction with thioredoxin domain containing 5 (TXNDC5) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
    Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 interacts with TXNDC5; predicted interaction to be within the endoplasmic reticulum and function as a thioredoxin reductase PubMed
    Envelope transmembrane glycoprotein gp41 env HIV-1 gp41 is identified to have a physical interaction with thioredoxin domain containing 5 (TXNDC5) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Go to the top of the page

    Interactions

    Go to the top of the page Help
    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Go to the top of the page Help

    Markers

    Readthrough BLOC1S5-TXNDC5

    Readthrough gene: BLOC1S5-TXNDC5, Included gene: BLOC1S5

    Homology

    Clone Names

    • MGC3178, FLJ21789

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein disulfide isomerase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein disulfide isomerase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein-disulfide reductase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in negative regulation of apoptotic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in protein folding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in azurophil granule lumen TAS
    Traceable Author Statement
    more info
    		  
    is_active_in endoplasmic reticulum IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endoplasmic reticulum TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in endoplasmic reticulum lumen ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    located_in lysosomal lumen TAS
    Traceable Author Statement
    more info
    		  

    General protein information

    Go to the top of the page Help
    Preferred Names
    thioredoxin domain-containing protein 5
    Names
    ER protein 46
    endoplasmic reticulum protein ERp46
    endoplasmic reticulum resident protein 46
    endothelial protein disulphide isomerase
    epididymis secretory sperm binding protein
    protein disulfide isomerase family A, member 15
    thioredoxin domain containing 5 (endoplasmic reticulum)
    thioredoxin related protein
    thioredoxin-like protein p46
    NP_001139021.1
    NP_110437.2

    NCBI Reference Sequences (RefSeq)

    Go to the top of the page Help

    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.

    mRNA and Protein(s)

    1. NM_001145549.4 → NP_001139021.1  thioredoxin domain-containing protein 5 isoform 3

      See identical proteins and their annotated locations for NP_001139021.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region and uses a downstream start codon, compared to variant 1. The resulting isoform (3) is shorter at the N-terminus, compared to isoform 1.
      Source sequence(s)
      AK315598, AY358646, BQ181185
      Consensus CDS
      CCDS47369.1
      UniProtKB/TrEMBL
      A0A024QZV0, Q86UY0
      Related
      ENSP00000420784.1, ENST00000473453.2
      Conserved Domains (2) summary
      cd03005
      Location:82 → 182
      PDI_a_ERp46; PDIa family, endoplasmic reticulum protein 46 (ERp46) subfamily; ERp46 is an ER-resident protein containing three redox active TRX domains. Yeast complementation studies show that ERp46 can substitute for protein disulfide isomerase (PDI) function in ...
      cl00388
      Location:2 → 56
      Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold

    2. NM_030810.5 → NP_110437.2  thioredoxin domain-containing protein 5 isoform 1 precursor

      See identical proteins and their annotated locations for NP_110437.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AY358646, BQ181185
      Consensus CDS
      CCDS4505.1
      UniProtKB/Swiss-Prot
      B2RDM2, Q5TCQ0, Q8NBS9, Q8ND33, Q8TCT2, Q9BVH9
      UniProtKB/TrEMBL
      Q658S9
      Related
      ENSP00000369081.4, ENST00000379757.9
      Conserved Domains (2) summary
      cd03005
      Location:190 → 290
      PDI_a_ERp46; PDIa family, endoplasmic reticulum protein 46 (ERp46) subfamily; ERp46 is an ER-resident protein containing three redox active TRX domains. Yeast complementation studies show that ERp46 can substitute for protein disulfide isomerase (PDI) function in ...
      TIGR01130
      Location:66 → 432
      ER_PDI_fam; protein disulfide isomerase, eukaryotic

    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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      7881517..7910788 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      7750266..7779537 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_022085.3: Suppressed sequence

      Description
      NM_022085.3: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8NBS9.2 GenPept UniProtKB/Swiss-Prot:Q8NBS9

    Gene LinkOut

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

    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous