Glyoxylate reductase/hydroxypyruvate reductase (GRHPR)
The protein contains 328 amino acids for an estimated molecular weight of 35668 Da.
Enzyme with hydroxy-pyruvate reductase, glyoxylate reductase and D-glycerate dehydrogenase enzymatic activities. Reduces hydroxypyruvate to D-glycerate, glyoxylate to glycolate oxidizes D-glycerate to hydroxypyruvate. (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.
- 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.
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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| Variant | Description |
|---|---|
| dbSNP:rs12002324 |
The reference OMIM entry for this protein is 260000
Hyperoxaluria, primary, type ii; hp2
Oxalosis ii
Glyceric aciduria
Glyoxylate reductase/hydroxypyruvate reductase deficiency
D-glycerate dehydrogenase deficiency
A number sign (#) is used with this entry because of evidence that type II primary hyperoxaluria (HP2) can be caused by homozygous or compound heterozygous mutation in the glyoxylate reductase/hydroxypyruvate reductase gene (GRHPR; 604296) on chromosome 9p13. For a discussion of genetic heterogeneity of primary hyperoxaluria, see 259900.
CLINICAL FEATURES
Seargeant et al. (1991) reported 8 HP2 patients who belonged to 3 Saulteaux-Ojibway Canadian Indian families living in 2 isolated communities in northwestern Ontario. All had increased urinary oxalic acid and L-glyceric acid. Four patients presented with symptoms resulting from calcium oxalate nephrolithiasis, including dysuria, hematuria, and urinary tract infections in infancy or early childhood; 3 did not have recurrences. The other 4 affected patients were free of symptoms, suggesting that HP2 may be a much milder disease with a better long-term prognosis for renal function than HP1 (259900). Seargeant et al. (1991) noted that 7 of 8 previously reported patients (Williams and Smith, 1968 and Chalmers et al., 1984) had renal calculi between 18 months and 24 years of age. One patient seemed to have had no symptoms and was identified only because his younger brother had the disorder (Chalmers et al., 1984). Kemper et al. (1997) stated that only 24 patients with primary hyperoxaluria type II had been reported, and noted that the disorder should be considered in any patient presenting with urolithiasis or nephrocalcinosis due to hyperoxaluria. The metabolic defect is deficiency of D-glycerate dehydrogenase/glyoxylate reductase leading to characteristic hyperoxaluria and excretion of L-glycerate, the cornerstone of diagnosis of this form of primary hyperoxaluria. Although development of terminal renal failure may be less common than in type I primary hyperoxaluria, chronic as well as terminal renal insufficiency has been described. Therefore, specific therapeutic measures should aim at reduction of urinary calcium oxalate saturation by potassium citrate or pyrophosphate to reduce the incidence of nephrolithiasis and nephrocalcinosis and thus improve renal survival. Secondary complications (obstruction, urinary tract infections, and pyelonephritis) must be avoided. In patients with terminal renal failure, renal transplantation seems to carry a high risk of disease recurrence. Takayama et al. (2014) reported 4 Japanese patients with HP2. The patients developed symptoms of hematuria or urinary tract infection between 10 months and 3 years of age. All developed stones in the kidney or bladder, but only 1 patient showed renal parenchymal calcifications. Laboratory studies showed increased urinary oxalate and L-glycerate. All patients had normal renal function at follow-up between 7 and 25 years of age.BIOCHEMICAL FEATURES
Williams and Smith (1971) presented evidence that in HP2, hydroxypyruvate, present in excess because of deficiency in the enzyme that converts it to D-glycerate, stimulates oxidation of glycolate to oxalate, and decreases reduction of glyoxylate to glycolate. This is a novel explanation for the phenotypic consequences of a garrodian inborn error of metabolism. Van Schaftingen et al. (1989) presented evidence that D-glycerate dehydrogenase should be considered an NADPH-linked reductase. This property accounts for the function of the enzyme, which is to maintain the cytosolic concentration of hydroxypyruvate and glyoxylate at a very low level, thus preve ... 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 260000 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed