L-xylulose reductase (DCXR)
The protein contains 244 amino acids for an estimated molecular weight of 25913 Da.
Catalyzes the NADPH-dependent reduction of several pentoses, tetroses, trioses, alpha-dicarbonyl compounds and L-xylulose. Participates in the uronate cycle of glucose metabolism. May play a role in the water absorption and cellular osmoregulation in the proximal renal tubules by producing xylitol, an osmolyte, thereby preventing osmolytic stress from occurring in the renal tubules. (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.
- 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.
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.
This protein is annotated as membranous in Gene Ontology.
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Biological Process
D-xylose metabolic process
Glucose metabolic process
Glucuronate catabolic process to xylulose 5-phosphate
NADP metabolic process
Oxidation-reduction process
Positive regulation of reactive oxygen species metabolic process
Protein homotetramerization
Xylulose metabolic process
Cellular Component
Brush border
Cytoplasmic microtubule
Extracellular exosome
Membrane
Microvillus
Nucleus
Plasma membrane
The reference OMIM entry for this protein is 260800
Pentosuria; pntsu
L-xylulosuria
Xylitol dehydrogenase deficiency
L-xylulose reductase deficiency
A number sign (#) is used with this entry because pentosuria (PNTSU) is caused by homozygous or compound heterozygous mutation in the DCXR gene (608347) on chromosome 17q25.
DESCRIPTION
Essential pentosuria is an inborn error of metabolism in which 1 to 4 gm of the pentose L-xylulose is excreted in the urine each day. It is a benign condition that occurs principally in individuals of Ashkenazi Jewish descent (summary by Hiatt, 2001).BIOCHEMICAL FEATURES
Levene and La Forge (1914) showed that the excreted pentose in pentosuria is L-xylulose. By direct biochemical means applied to erythrocytes, Wang and Van Eys (1970) demonstrated that the basic fault in pentosuria concerns NADP-linked xylitol dehydrogenase, the enzyme that catalyzes the conversion of L-xylulose to xylitol. Although the glucuronic acid pathway, in which metabolic block is situated, was elucidated in the 1950s (Touster, 1959) and the site of the metabolic block became evident, actual demonstration of the responsible enzyme deficiency required the finding of L-xylulose reductase activity in normal red cells. Biopsy of liver and kidney, which had the highest enzyme activity, could not be justified in this benign condition. Lane (1985) found that 2 distinct L-xylulose reductases are produced in human tissues. The major isozyme is missing in pentosuria, whereas the minor isozyme, which presumably is coded by a separate gene, is retained. The major isozyme occurs in both the cytosol and the mitochondria, whereas the minor isozyme is limited to the cytosol (Lane and Jenkins, 1985). Heterozygotes can be recognized by demonstrating either an intermediate level of erythrocyte activity of xylitol dehydrogenase or increased urinary or serum L-xylulose, or both, in a glucuronolactone loading test (Hiatt, 2001).INHERITANCE
The inheritance pattern of pentosuria is autosomal recessive (Pierce et al., 2011). Politzer and Fleischmann (1962) suggested dominant inheritance for pentosuria in 1 Lebanese family. Lane and Jenkins (1985) restudied the family, using an improved assay for red cell enzyme in the identification of heterozygotes, and concluded that pseudodominance of the usual recessive trait was actually the case. They discussed the possibility that the Lebanese and Ashkenazim gene may have the same mutation, i.e., descended from a single mutation in the past. The minimum estimate of the frequency of the pentosuria allele in Ashkenazim was calculated to be 0.0127.MOLECULAR GENETICS
In 9 probands of Ashkenazi Jewish descent with pentosuria, Pierce et al. (2011) identified homozygous or compound heterozygous loss-of-function mutations in the DCXR gene (608347.0001 and 608347.0002). Patient cells showed a complete lack of the DCXR protein. The allele frequency of the 2 alleles combined among 1,067 individuals of Ashkenazi Jewish descent was 0.0173, leading to an expected frequency of pentosuria of 1 in 3,300 individuals in this population. These families had originally been studied by Margaret Lasker in the mid-20th century.POPULATION GENETICS
Pentosuria occurs almost exclusively in individuals of Ashkenazi Jewish descent. The frequency in American Jews is estimated at 1 in 2,000 to 2,500 (Hiatt, 2001). Khachadurian (1962) and Politzer and Fleischmann (1962) described pentosuria in Lebanese families. Soyama and Furukawa (1985) described a Japanese case of pentosuria.HISTORY
Pentosuria was one of the original 4 inborn ... 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 260800 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed