GDP-L-fucose synthase (TSTA3)
The protein contains 321 amino acids for an estimated molecular weight of 35893 Da.
Catalyzes the two-step NADP-dependent conversion of GDP-4-dehydro-6-deoxy-D-mannose to GDP-fucose, involving an epimerase and a reductase reaction. (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.
- 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.
- 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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The reference OMIM entry for this protein is 137020
Tissue-specific transplantation antigen 3; tsta3
Gdp-keto-6-deoxymannose 3,5-epimerase, 4-reductase
Red cell nadp(h)-binding protein
Fx
Red cells contain a specific NADP(H)-binding protein, designated as FX (Morelli and De Flora, 1977). Lenzerini et al. (1981) concluded that there is a common genetic polymorphism at the locus or loci that control the level of the FX protein. The conclusion was based on the finding of large variation in FX levels in unrelated persons and a very strong 'family effect.' That a major X-linked locus is not involved was indicated by the positive correlation between fathers and sons, and the lack of significant correlation in the values of FX between maternal grandfathers and their grandsons.
CLONING
Tonetti et al. (1996) used PCR to obtain the complete sequence of the human FX cDNA. They found that the FX gene encodes a 320-amino acid polypeptide with a predicted molecular mass of 35.7 kD. This finding is in agreement with previous data showing that the FX protein forms a homodimer of 68 kD. Database analysis demonstrated that human FX protein is 92.6% identical to the mouse tumor rejection antigen P35B and has a lower level of homology to 3 bacterial proteins, 1 of which may be involved in sugar metabolism.GENE FUNCTION
Tonetti et al. (1996) examined the role of FX in GDP-D-mannose metabolism. GDP-fucose is synthesized from GDP-mannose in a 3-step pathway. The first step is catalyzed by GDP-mannose 4,6-dehydratase, or GMD (602884). The second and third steps are an epimerization and a reduction reaction, respectively. The authors found that FX can catalyze both the epimerase and the reductase reactions, converting GDP-4-keto-6-D-deoxymannose to GDP-L-fucose. GDP-L-fucose is the substrate of several fucosyltransferases involved in the expression of many glycoconjugates, including blood group ABH antigens and developmental adhesion antigens. Using purified GMD and FX, Sullivan et al. (1998) showed that the 2 proteins alone are sufficient to convert GDP-mannose to GDP-fucose in vitro. They suggested that mutations in one of these 2 enzymes may cause leukocyte adhesion deficiency, type II (LAD2; 266265), since cells from 2 LAD2 patients appeared to have a specific defect in this pathway.MAPPING
By fluorescence in situ hybridization, Sullivan et al. (1998) mapped the FX gene to 8q24.3.ANIMAL MODEL
Smith et al. (2002) induced a null mutation in the Fx locus in mice. Mice with this mutation exhibited complete deficiency of cellular fucosylation and variable intrauterine fatality. Liveborn Fx-null mice exhibited postnatal failure to thrive that was suppressed with a fucose-supplemented diet. Homozygous adults suffered from an extreme neutrophilia, myeloproliferation, and absence of leukocyte selectin ligand (600738) expression reminiscent of LAD2. Restoration of leukocyte and endothelial selectin ligand expression, general cellular fucosylation, and normal postnatal physiology was achieved by modulating dietary fucose to supply a salvage pathway for GDP-fucose synthesis. ... 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
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 137020 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed