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

Summary

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
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Genomic context

Location:: 6p24.3

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (7881517..7910788, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (7750266..7779537, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (7881750..7911021, complement)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
The role and mechanism of TXNDC5 in diseases.
Title: The role and mechanism of TXNDC5 in diseases.
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.
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.
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.
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.
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.
Taken together, by linking HSC70 and NF-kappaB signaling, TXNDC5 plays a pro-inflammatory role in rheumatoid arthritis synovial fibroblasts, highlighting a potential approach to treat rheumatoid arthritis by blocking the TXNDC5/HSC70 interaction.
Title: TXNDC5 synergizes with HSC70 to exacerbate the inflammatory phenotype of synovial fibroblasts in rheumatoid arthritis through NF-κB signaling.
TXNDC5 mRNA and protein were highly upregulated in failing human left ventricles. TXNDC5 mRNA and protein were increased in human cardiac fibroblasts under transforming growth factor beta1 stimulation in vitro.TXNDC5 knockdown attenuated TGFbeta1-induced activation and ECM protein upregulation independent of SMAD3, but increasing expression of TXNDC5 triggered activation and proliferation and increased ECM protein prod...
Title: Endoplasmic Reticulum Protein TXNDC5 Augments Myocardial Fibrosis by Facilitating Extracellular Matrix Protein Folding and Redox-Sensitive Cardiac Fibroblast Activation.

Submit: New GeneRIF Correction See all GeneRIFs (35)

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)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-13193 (e-PCR)
- UniSTS:6694

RH26506 (e-PCR)
- UniSTS:86358

A002L04 (e-PCR)
- UniSTS:3730

RH46813 (e-PCR)
- UniSTS:47767

SHGC-33534 (e-PCR)
- UniSTS:63138

AL021859 (e-PCR)
- UniSTS:53699

NIB594 (e-PCR)
- UniSTS:19406

Readthrough BLOC1S5-TXNDC5

Readthrough gene: BLOC1S5-TXNDC5, Included gene: BLOC1S5

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 more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in lysosomal lumen	TAS Traceable Author Statement more info

General protein information

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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

EC 5.3.4.1

NP_110437.2

EC 5.3.4.1

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)

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
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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

7881517..7910788 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060930.1 Alternate T2T-CHM13v2.0

Range

7750266..7779537 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

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.