TMX1 thioredoxin related transmembrane protein 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TMX1provided by HGNC
Official Full Name: thioredoxin related transmembrane protein 1provided by HGNC
Primary source: HGNC:HGNC:15487
See related: Ensembl:ENSG00000139921 MIM:610527; AllianceGenome:HGNC:15487
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TMX; TXNDC; PDIA11; TXNDC1
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 ER-signal sequence, a catalytically active thioredoxin domain, and one transmembrane domain. Unlike most members of this gene family, it lacks a C-terminal ER-retention sequence. The mature membrane-bound protein can both oxidize and reduce disulfide bonds and acts selectively on membrane-associated polypeptides. [provided by RefSeq, Jan 2017]
Expression: Ubiquitous expression in urinary bladder (RPKM 15.6), colon (RPKM 14.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q22.1

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (51240247..51257655)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (45446717..45464426)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (51706965..51724373)

Chromosome 14 - NC_000014.9 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 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?

TMX family genes and their association with prognosis, immune infiltration, and chemotherapy in human pan-cancer.
Title: TMX family genes and their association with prognosis, immune infiltration, and chemotherapy in human pan-cancer.
Thiol Isomerases Orchestrate Thrombosis and Hemostasis.
Title: Thiol Isomerases Orchestrate Thrombosis and Hemostasis.
Data show that TMX1 expression is upregulated in melanoma cell lines and patient samples. TMX knockdown altered mitochondrial organization, enhanced bioenergetics, and elevated mitochondrial- and NOX4-derived ROS. The TMX-knockdown-induced oxidative stress suppressed melanoma proliferation, migration, and xenograft tumor growth by inhibiting NFAT1. TMX1 is associated with poor disease outcome.
Title: Redox signals at the ER-mitochondria interface control melanoma progression.
TMX1 selectively intervenes in clearance of membrane-tethered Endoplasmic Reticulum-Associated Degradation substrates. TMX1 preferentially acts on membrane-tethered folding-defective polypeptides essentially ignoring the same misfolded ectodomains, when not associated to the Endoplasmic Reticulum membrane.
Title: The reductase TMX1 contributes to ERAD by preferentially acting on membrane-associated folding-defective polypeptides.
TMX1 increases mitochondrial ATP production and apoptosis progression.
Title: TMX1 determines cancer cell metabolism as a thiol-based modulator of ER-mitochondria Ca2+ flux.
Here we show that TMX1, one of the few transmembrane members of the family, forms functional complexes with the ER lectin calnexin and preferentially intervenes during maturation of cysteine-containing, membrane-associated proteins
Title: Division of labor among oxidoreductases: TMX1 preferentially acts on transmembrane polypeptides.
We conclude that TMX plays a major role in host defense under the type of inflammatory conditions associated with oxidative stress.
Title: The protective role of the transmembrane thioredoxin-related protein TMX in inflammatory liver injury.
the silencing of TMX in the prostatic cell line DU145 reduced the sensitivity of the cells to ricin intoxication further confirming a role for this enzyme in intracellular ricin activation.
Title: Reductive activation of type 2 ribosome-inactivating proteins is promoted by transmembrane thioredoxin-related protein.
TMX1 is enriched on the mitochondria-associated membrane. Targeting TMX to the MAM requires palmitoylation of two membrane-proximal cytosolic cysteines.
Title: Palmitoylated TMX and calnexin target to the mitochondria-associated membrane.
These results suggest a specific role for transmembrane thioredoxin-related protein TMX and its mechanism of action in redox-based ER quality control.
Title: Physical and functional interaction of transmembrane thioredoxin-related protein with major histocompatibility complex class I heavy chain: redox-based protein quality control and its potential relevance to immune responses.

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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 gp160, precursor	env	HIV-1 gp160 interacts with TMX1; predicted interaction to be within the endoplasmic reticulum and function as thioredoxin reductase	PubMed

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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

RH65082 (e-PCR)
- UniSTS:91736

RH93716 (e-PCR)
- UniSTS:92842

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables disulfide oxidoreductase activity	IBA Inferred from Biological aspect of Ancestor more info
enables disulfide oxidoreductase activity	IDA Inferred from Direct Assay more info	PubMed
enables enzyme inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein disulfide isomerase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein-disulfide reductase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in negative regulation of platelet aggregation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of triglyceride biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of ERAD pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of calcium ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in endomembrane system	IBA Inferred from Biological aspect of Ancestor more info
is_active_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	IEA Inferred from Electronic Annotation more info
is_active_in mitochondria-associated endoplasmic reticulum membrane contact site	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: thioredoxin-related transmembrane protein 1

Names: protein disulfide isomerase family A, member 11; protein disulfide-isomerase TMX1; thioredoxin domain containing 1; thioredoxin domain-containing protein 1; transmembrane Trx-related protein

NP_110382.3

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_030755.5 → NP_110382.3 thioredoxin-related transmembrane protein 1 precursor

See identical proteins and their annotated locations for NP_110382.3

Status: VALIDATED

Source sequence(s)

AB048246, AL591807, BC056874, BU754378

Consensus CDS

CCDS41953.1

UniProtKB/Swiss-Prot

B2R7A4, Q8N487, Q8NBN5, Q9H3N1, Q9Y4T6

Related

ENSP00000393316.2, ENST00000457354.7

Conserved Domains (1) summary

cd02994
Location:29 → 129

PDI_a_TMX; PDIa family, TMX subfamily; composed of proteins similar to the TRX-related human transmembrane protein, TMX. TMX is a type I integral membrane protein; the N-terminal redox active TRX domain is present in the endoplasmic reticulum (ER) lumen while the ...