Ubiquitin-like protein 4A (UBL4A)
The protein contains 157 amino acids for an estimated molecular weight of 17777 Da.
As part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, maintains misfolded and hydrophobic patches-containing proteins in a soluble state and participates in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation (PubMed:20676083, PubMed:21636303, PubMed:21743475, PubMed:28104892). The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum (PubMed:20676083, PubMed:28104892, PubMed:25535373). Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated and sorted to the proteasome (PubMed:28104892). Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum (PubMed:21743475). The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these ret (updated: June 17, 2020)
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.
- 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.
- 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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The reference OMIM entry for this protein is 312070
Ubiquitin-like 4a; ubl4a
Ubl4
Gdx
Dxs254e
CLONING
Martini et al. (1986) isolated a ubiquitously transcribed region, which they provisionally named the GDX gene, about 40 kb downstream of the glucose-6-phosphate dehydrogenase gene (G6PD; 305900) on the X chromosome. Transcripts of this gene were detected in up to 10 different cell types, suggesting to Martini et al. (1986) that it, like G6PD, is a housekeeping gene. Alcalay and Toniolo (1987) characterized 2 genes, P3 (312090) and GDX, on Xq28. Several overlapping lambda and cosmid clones linked them to the G6PD gene. Both lie about 40 kb downstream from the G6PD gene. P3 and GDX show no sequence homology between themselves or G6PD or to any previously described genes, but they appear to have been conserved in evolution. Their expression is ubiquitous. In agreement with the sequence of many housekeeping genes, their promoter region is GC rich and lacks signals such as TATA and CAT boxes. GDX encodes a protein of 157 amino acids. It shows strong similarity in its 72 N-terminal amino acids to ubiquitin (191339), a highly conserved 76-amino acid protein. Moreover, in the middle of the C-terminus moiety of the GDX protein, similarities to the thyroglobulin (188450) hormonogenic site, the sequence that surrounds the tyrosines that will form thyroxine, have been demonstrated. These similarities suggested to Alcalay and Toniolo (1987) that the GDX protein plays a key and specific role in vital functions of the cell.GENE STRUCTURE
Martini et al. (1986) found that the GDX is transcribed in the same direction as the upstream G6PD gene. Alcalay and Toniolo (1987) found that protein P3 and protein GDX are contained within 7 kb of DNA. The 3-prime end of the P3 gene is 0.5 kb upstream from the GDX gene. Filippi et al. (1990) showed that the murine equivalents of the P3 and GDX genes lie in similar close physical proximity on the mouse X chromosome. Furthermore, the relative orientation of the 2 genes is the same. The sequence in both coding and noncoding regions is highly conserved.MAPPING
Alcalay and Toniolo (1987) mapped the GDX gene to chromosome Xq28.GENE FUNCTION
Mariappan et al. (2010) identified a conserved 3-protein complex composed of BAT3 (142590), TRC35 (612056), and UBL4A that facilitates tail-anchored protein capture by TRC40 (601913). This BAT3 complex is recruited to ribosomes synthesizing membrane proteins, interacts with the transmembrane domains of newly released tail-anchored proteins, and transfers them to TRC40 for targeting. Depletion of the BAT3 complex allows non-TRC40 factors to compete for tail-anchored proteins, explaining their mislocalization in the analogous yeast deletion strains. Thus, the BAT3 complex acts as a transmembrane domain-selective chaperone that effectively channels tail-anchored proteins to the TRC40 insertion pathway. ... More on the omim web site
June 29, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
July 2, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 312070 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed