Protein disulfide-isomerase TMX3 (TMX3)
The protein contains 454 amino acids for an estimated molecular weight of 51872 Da.
Probable disulfide isomerase, which participates in the folding of proteins containing disulfide bonds. May act as a dithiol oxidase. (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| dbSNP:rs11557684 |
No binding partner found
Biological Process
Cell redox homeostasis
Peptidyl-cysteine oxidation
Platelet degranulation
Protein folding
Response to endoplasmic reticulum stress
The reference OMIM entry for this protein is 616102
Thioredoxin-related transmembrane protein 3; tmx3
Thioredoxin domain-containing protein 10; txndc10
Kiaa1830
DESCRIPTION
Members of the protein-disulfide isomerase (PDI; see 176790) family, like TMX3, are endoplasmic reticulum (ER)-resident proteins that catalyze the formation of disulfide bonds in newly synthesized proteins (Haugstetter et al., 2005).CLONING
By sequencing clones obtained from a size-fractionated adult brain cDNA library, Nagase et al. (2001) cloned TMX3, which they designated KIAA1830. The deduced 486-amino acid protein contains motifs related to thioredoxin (TXN; 187700) and calsequestrin (CASQ1; 114250). RT-PCR ELISA detected TMX3 expression in all adult and fetal tissues and specific adult brain regions examined. High expression was found in whole adult brain, lung, and liver. Expression in whole fetal brain and liver was much lower than that detected in adult brain and liver. Haugstetter et al. (2005) reported that human TMX3 contains 454 amino acids and has an N-terminal ER signal peptide, followed by a catalytic TXN-like domain, a transmembrane domain, and a C-terminal tail that ends in a typical KKxx ER-retrieval motif. Cleavage of the signal peptide results in a mature 430-amino acid protein with an N-terminal catalytic domain. Database analysis revealed widespread TMX3 expression, and Northern blot analysis of 8 human tissues showed highest expression of 4.0- and 5.1-kb transcripts in heart and skeletal muscle. Immunofluorescence microscopy detected endogenous monkey Tmx3 and epitope-tagged human TMX3 expressed in a reticular pattern typical of the ER in Vero green monkey kidney cells. Orthologs of TMX3 were detected in several vertebrates, urochordates, arthropods, and nematodes, but not in fungi or lower organisms. The THX-like domain was the most conserved region. By in situ hybridization in the mouse eye, Chao et al. (2010) observed robust Tmx3 expression at embryonic days 13.5 to 16.5 in regions corresponding to the future retina and lens epithelium. At postnatal day 4, Tmx3 expression was present in at least the outer retinal layer of the eye. In addition to being expressed in the developing eye, Tmx3 was also expressed in several other tissues during embryogenesis, including brain, kidney, and lung.GENE STRUCTURE
Haugstetter et al. (2005) reported that the TMX3 gene contains 16 exons and spans 41.44 kb.MAPPING
Haugstetter et al. (2005) stated that the TMX3 gene maps to chromosome 18q22.1.GENE FUNCTION
Using protein expressed in E. coli for in vitro assay, Haugstetter et al. (2005) found that the isolated ER luminal domain of TMX3 catalyzed oxidation of a model decapeptide containing 2 cysteines. However, the oxidation reaction was significantly slower than that obtained with PDI. The redox potential of TMX3 was similar to that of other human PDI family members. In HEK and HeLa cells, TMX3 was predominantly found in the reduced form, but a significant fraction was detected in the oxidized form.MOLECULAR GENETICS
For discussion of a possible association between microphthalmia with coloboma (see 300345) and variation in the TMX3 gene, see 616102.0001.ANIMAL MODEL
Chao et al. (2010) used 2 antisense morpholinos targeted against the zebrafish ortholog of TMX3, zgc:110025, to examine the effects of reduced gene expression in eye development. Morphant larvae resulting from both morpholinos had significantly smaller eye sizes, mostly bilateral and with a penetrance ranging from 50 to 80%, as well as markedly reduced labeling with islet- ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 616102 was added.