GDP-mannose 4,6 dehydratase (GMDS)
The protein contains 372 amino acids for an estimated molecular weight of 41950 Da.
Catalyzes the conversion of GDP-D-mannose to GDP-4-dehydro-6-deoxy-D-mannose. (updated: April 1, 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.
- 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 602884
Gdp-mannose 4,6-dehydratase; gmds
Gmd
DESCRIPTION
GDP-mannose 4,6-dehydratase (GMD; EC 4.2.1.47) catalyzes the conversion of GDP-mannose to GDP-4-keto-6-deoxymannose, the first step in the synthesis of GDP-fucose from GDP-mannose, using NADP+ as a cofactor. The second and third steps of the pathway are catalyzed by a single enzyme, GDP-keto-6-deoxymannose 3,5-epimerase, 4-reductase, designated FX in humans (137020).CLONING
By BLAST searching, Sullivan et al. (1998) identified a partial mouse cDNA with homology to E. coli GMD. Using PCR with primers based on conserved regions of the protein, they isolated promyelocytic cell line cDNAs encoding human GMD. The sequence of the predicted human protein is 61% identical to that of E. coli GMD. Northern blot analysis revealed that GMD is expressed as a 1.7-kb transcript in all tissues examined. Sullivan et al. (1998) demonstrated that human GMD cDNA complements the defect in Lec13, a Chinese hamster ovary cell line deficient in GMD activity. Using purified GMD and FX, the authors showed that the 2 proteins alone are sufficient to convert GDP-mannose to GDP-fucose in vitro. Sullivan et al. (1998) 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. Ohyama et al. (1998) also isolated GMD cDNAs. By Northern analysis, they showed that GMD mRNA is absent from Lec13 cells.MAPPING
By fluorescence in situ hybridization, Sullivan et al. (1998) mapped the GMDS gene to chromosome 6p25.MOLECULAR GENETICS
In an analysis of chromosome 6p25.3 copy number variation, Aldinger et al. (2009) examined brain imaging studies from 12 individuals with chromosome 6pter-p24 deletion syndrome (612582). All had abnormalities on MRI, showing classic or mild Dandy-Walker malformation, mega cisterna magna, or cerebellar vermis hypoplasia. The phenotype data showed consistently more severe phenotypes among individuals with large compared to small deletions, suggesting contributions from more than 1 causative gene in the region; in addition, all 12 deletions involved the FOXC1 gene plus at least 2 exons of the GMDS gene, implicating 1 or both of these genes as having a previously unrecognized role in cerebellar development. ... 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602884 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed