Endoplasmic reticulum resident protein 44 (ERP44)
The protein contains 406 amino acids for an estimated molecular weight of 46971 Da.
Mediates thiol-dependent retention in the early secretory pathway, forming mixed disulfides with substrate proteins through its conserved CRFS motif. Inhibits the calcium channel activity of ITPR1. May have a role in the control of oxidative protein folding in the endoplasmic reticulum. Required to retain ERO1A and ERO1B in the endoplasmic reticulum. (updated: Nov. 22, 2017)
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.
- 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.
- 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.
- 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.
- 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.
- 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.
| 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.
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Biological Process
Cell redox homeostasis
Glycoprotein metabolic process
Neutrophil degranulation
Protein folding
Response to endoplasmic reticulum stress
Response to unfolded protein
The reference OMIM entry for this protein is 609170
Thioredoxin domain-containing protein 4; txndc4
Endoplasmic reticulum resident protein, 44-kd; erp44
Kiaa0573
CLONING
By sequencing clones obtained from a size-fractionated human brain cDNA library, Nagase et al. (1998) cloned TXNDC4, which they designated KIAA0573. The transcript contains a repetitive element in the 3-prime UTR, and the deduced 451-amino acid protein has an apparent molecular mass of 50 kD, as estimated by SDS-PAGE. KIAA0573 shares weak homology with barley protein disulfide isomerase precursor. RT-PCR detected robust expression in all tissues examined. By peptide sequencing of proteins immunoprecipitated with ERO1L-alpha (ERO1L; 615435) following its overexpression in HeLa cells, followed by database analysis and screening HeLa and neuroblastoma cell line cDNA libraries, Anelli et al. (2002) obtained a full-length cDNA encoding TXNDC4, which they called ERp44. The deduced 436-amino acid protein has an N-terminal endoplasmic reticulum (ER) targeting signal sequence. After cleavage, the calculated molecular mass of ERp44 is 43.9 kD. ERp44 also contains a thioredoxin (187700)-like domain, which includes a CRFS motif; a calsequestrin (114250)-like domain; and a C-terminal ER retention signal (RDEL). The CRFS motif is present in mouse, fly, and nematode ERp44 homologs.GENE FUNCTION
Anelli et al. (2002) found that ERp44 formed mixed disulfides with proteins involved in oxidative protein folding in the ER, including ERO1L-alpha and ERO1L-beta (ERO1LB; 615437), and with cargo folding intermediates. While the interaction with transport-competent IgK chains (147200) was transient, ERp44 bound more stably with IgJ chains (147790), which are retained in the ER and are eventually degraded by proteasomes. ERp44 did not bind a short-lived ribophorin (see 180470) mutant lacking cysteines. Overexpression of ERp44 altered the equilibrium of different ERO1L-alpha isoforms, suggesting that ERp44 may be involved in control of oxidative protein folding. Higo et al. (2005) found that ERp44 interacted directly with the third luminal loop of inositol 1,4,5-trisphosphate receptor type 1 (IP3R1; 147265). The interaction was dependent on pH, Ca(2+) concentration, and redox state, with the presence of free cysteine residues in the loop of IP3R1 required. Ca(2+)-imaging experiments and single-channel recording of IP3R1 activity with a planar lipid bilayer system demonstrated that IP3R1 was directly inhibited by ERp44. Higo et al. (2005) concluded that ERp44 senses the environment in the ER lumen and modulates IP3R1 activity accordingly, which in turn contributes to regulating both intraluminal conditions and the complex patterns of cytosolic Ca(2+) concentrations.GENE STRUCTURE
Anelli et al. (2002) determined that the TXNDC4 gene contains 12 exons.MAPPING
By radiation hybrid analysis, Nagase et al. (1998) mapped the TXNDC4 gene to chromosome 9. Anelli et al. (2002) mapped the TXNDC4 gene to chromosome 9q22-q32 by genomic sequence analysis. ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 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 609170 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed