Thioredoxin domain-containing protein 5 (TXNDC5)

The protein contains 432 amino acids for an estimated molecular weight of 47629 Da.

 

Possesses thioredoxin activity. Has been shown to reduce insulin disulfide bonds. Also complements protein disulfide-isomerase deficiency in yeast (By similarity). (updated: April 1, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. 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.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 29%
Model score: 51

(right-click above to access to more options from the contextual menu)

The reference OMIM entry for this protein is 616412

Thioredoxin domain-containing protein 5; txndc5
Endoplasmic reticulum protein, 46-kd; erp46
Endothelial protein disulfide isomerase; endopdi
Hepatocellular carcinoma 2; hcc2

DESCRIPTION

TXNDC5 belongs to the protein disulfide isomerase (PDI; see 608012) family of enzymes that reside in the endoplasmic reticulum (ER) and assist in formation of disulfide bonds and in correct folding of nascent polypeptides (Knoblach et al., 2003; Sullivan et al., 2003).

CLONING

By examining serial analysis of gene expression (SAGE) libraries for genes highly expressed in endothelial cells, followed by RT-PCR of total RNA isolated from human dermal microvascular endothelial cells (HDMECs), Sullivan et al. (2003) cloned TXNDC5, which they designated ENDOPDI. The deduced protein contains an N-terminal signal sequence, followed by 3 thioredoxin (TXN; 187700) motifs and a C-terminal ER retention signal (KDEL). RNase protection analysis detected higher ENDOPDI expression in human endothelial cells than in other human cells and cell lines examined. RNA dot blot analysis showed ENDOPDI expression in 20 of 72 tissues examined, with highest expression in lymph node, followed by stomach and heart. In situ hybridization revealed ENDOPDI in vasculature of human melanomas, syncytiotrophoblasts of placenta, macrophages and microvasculature of atherosclerotic plaques, and keratinocytes of hair follicles. Database analysis detected orthologs of ENDOPDI in mammals, frogs, and insects. Knoblach et al. (2003) cloned mouse Erp46. The deduced protein has an N-terminal hydrophobic signal sequence, followed by a hydrophobic stretch, 3 thioredoxin motifs, and a C-terminal ER retention signal. Northern blot analysis showed variable Erp46 expression in 8 mouse tissues, with highest expression in liver, and no expression in skeletal muscle. Western blot analysis detected Erp46 at an apparent molecular mass of 51 kD. In fractionated mouse liver, Erp46 expression was high in ER membranes compared with whole liver homogenates. Immunohistochemical analysis of McA-RH7777 rat hepatoma cells showed colocalization of Erp46 with an ER marker throughout the ER network and in cisternae of the nuclear envelope. Nissom et al. (2006) reported that full-length TXNDC5, which they called HCC2, contains 432 amino acids. By RT-PCR and 5-prime and 3-prime RACE, they identified a splice variant of HCC2 that was differentially upregulated in poorly defined hepatocellular carcinomas. The deduced 363-amino acid isoform has a calculated molecular mass of 40.7 kD. It is N-terminally truncated compared with full-length HCC2 and consequently lacks the predicted secretory signal and transmembrane domain. Quantitative RT-PCR detected variable expression of HCC2 in all human tissues examined, with highest expression in pancreas. HCC2 protein migrated with an apparent molecular mass of 55 kD in 2-dimensional gels.

GENE FUNCTION

Sullivan et al. (2003) found that hypoxia increased expression of ENDOPDI in HDMECs. Depletion of ENDOPDI via small interfering RNA increased hypoxia-induced apoptosis and necrosis in HDMECs and reduced secretion of adrenomedullin (ADM; 103275) and endothelin-1 (EDN1; 131240) and cell surface expression of CD105 (ENG; 131195), all of which protect endothelial cells from hypoxia-induced apoptosis. Knockdown of ENDOPDI had little effect on HDMEC survival in the resting state. Knoblach et al. (2003) found that mouse Erp46 rescued a PDI-deficient yeast strain, suggesting that Erp46 functions as a PDI in mammals. Using recombinant protein expressed in insect cells, Nissom et al. (2006) found that HCC2 showed reductase activity toward ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: Protein entry updated
Automatic update: OMIM entry 616412 was added.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed