UDP-glucose 4-epimerase (GALE)
The protein contains 348 amino acids for an estimated molecular weight of 38282 Da.
Catalyzes two distinct but analogous reactions: the reversible epimerization of UDP-glucose to UDP-galactose and the reversible epimerization of UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine. The reaction with UDP-Gal plays a critical role in the Leloir pathway of galactose catabolism in which galactose is converted to the glycolytic intermediate glucose 6-phosphate. It contributes to the catabolism of dietary galactose and enables the endogenous biosynthesis of both UDP-Gal and UDP-GalNAc when exogenous sources are limited. Both UDP-sugar interconversions are important in the synthesis of glycoproteins and glycolipids. (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
- 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.
- 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.
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.
The reference OMIM entry for this protein is 230350
Galactose epimerase deficiency
Gale deficiency
Galactosemia iii
Udp-galactose-4-epimerase deficiency
A number sign (#) is used with this entry because galactosemia III is caused by homozygous or compound heterozygous mutation in the UDP-galactose-4-epimerase gene (GALE; 606953) on chromosome 1p36.
DESCRIPTION
Epimerase-deficiency galactosemia was originally described as a benign condition in which GALE impairment is restricted to circulating red and white blood cells (Gitzelmann, 1972). Fibroblasts, liver, phytohemagglutinin-stimulated leukocyes, and Epstein Barr virus-transformed lymphoblasts from these patients all demonstrated normal or near-normal levels of GALE, leading to the designation 'peripheral' (or 'isolated') epimerase deficiency. A second form of epimerase deficiency became apparent in which a patient, despite normal GALT activity, presented with symptoms reminiscent of classic galactosemia and demonstrated severely impaired GALE activity in both red blood cells and fibroblasts (Holton et al., 1981). This form was designated 'generalized' epimerase deficiency. Openo et al. (2006) demonstrated that epimerase deficiency is in fact not a binary condition but is, rather, a continuum disorder. GALE encodes the third enzyme in the Leloir pathway of galactose metabolism. Galactosemia I is classic galactosemia (230400), caused by deficiency of the second enzyme in the Leloir pathway, galactose-1-phosphate uridylyl-transferase (GALT; 606999). Galactosemia II (230200) is caused by deficiency of the first enzyme in the Leloir pathway, galactokinase (GALK; 604313).CLINICAL FEATURES
Kalckar (1965) predicted some of the consequences of galactose epimerase deficiency. Gitzelmann (1972) reported galactose epimerase deficiency in a healthy infant who had elevated blood galactose on a screening exam. The parents had an intermediate level of enzymatic activity. The prognosis of the child was uncertain. Mitchell et al. (1975) reported that galactose epimerase deficiency had been identified in the peripheral blood of 7 persons in 3 families, and that no clinical abnormality was identified. Gitzelmann et al. (1976) reported 8 cases in 3 families. The probands were ascertained in newborn screening. Again, all were healthy. Galactose epimerase deficiency was limited to circulating blood cells, whereas epimerase activity in liver, cultured skin fibroblasts, and activated lymphocytes was normal. Heterozygotes had an intermediate level of enzyme. All 8 were of the cddee Rhesus genotype. This may merely reflect the high frequency of Rh-negativity in the population studied. However, linkage should be kept in mind. Gitzelmann and Hansen (1980) reported an Rh-positive case (1 out of 9) of epimerase deficiency, discovered in eastern Switzerland and Liechtenstein. Oyanagi et al. (1981) reported 3 Japanese families. Through newborn screening, Alano et al. (1998) identified a GALE-deficient patient of mixed Pakistani/European ancestry. He was clinically well in the neonatal period on a lactose-containing diet, and biochemical studies, including urine-reducing sugars and galactitol, were consistent with the diagnosis of peripheral GALE deficiency. Although early developmental milestones were met normally, he later showed significant developmental delays in both motor and language skills. Holton et al. (1981) reported a Pakistani baby with a severe form of galactosemia due to epimerase deficiency. The patient presented in the newborn period with clinical symptoms similar to classic galactosemia, including jaundice, vomiting, hypotonia, ... More on the omim web site
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 230350 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).