Malate dehydrogenase, cytoplasmic (MDH1)
The protein contains 334 amino acids for an estimated molecular weight of 36426 Da.
Catalyzes the reduction of aromatic alpha-keto acids in the presence of NADH (PubMed:3052244). Plays essential roles in the malate-aspartate shuttle and the tricarboxylic acid cycle, important in mitochondrial NADH supply for oxidative phosphorylation (PubMed:31538237). (updated: Feb. 10, 2021)
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.
- 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.
- 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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Biological Process
Carbohydrate metabolic process
Cellular carbohydrate metabolic process
Gluconeogenesis
Glucose metabolic process
Malate metabolic process
NAD metabolic process
NADH metabolic process
Oxaloacetate metabolic process
Pathogenesis
Small molecule metabolic process
Tricarboxylic acid cycle
Cellular Component
Centrosome
Cytoplasm
Cytosol
Extracellular exosome
Extracellular space
Mitochondrion
Myelin sheath
The reference OMIM entry for this protein is 154200
Malate dehydrogenase, soluble; mdh1
Malate dehydrogenase, cytoplasmic
DESCRIPTION
Malate dehydrogenase (EC 1.1.1.37) catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle. Two isozymes are known, one in the cytosol (MDH1) and the other in the mitochondria (MDH2; 154100) (summary by Tanaka et al., 1996).CLONING
Tanaka et al. (1996) isolated a human cDNA encoding a protein of 334 amino acids that showed 96% identity in amino acid sequence to murine cytosolic malate dehydrogenase. Among the adult human tissues examined by Northern blot analysis, heart and skeletal muscle expressed this gene most highly.MAPPING
MDH is syntenic with isocitrate dehydrogenase (147700) (Shows, 1972). Chu et al. (1975) presented cell-hybrid evidence for synteny of gal-1-PT, acid phosphatase, MDH1 and gal-plus-activator and for assignment to chromosome 2. By fluorescence in situ hybridization, Tanaka et al. (1996) mapped the MDH1 gene to chromosome 2p16. This localization was somewhat different from that earlier determined by less precise methods, i.e., analysis of enzyme activity in somatic cell hybrids and deletion mapping. In the mouse, the cytosolic form of malate dehydrogenase is determined by a gene symbolized Mor2 and the mitochondrial form by a gene symbolized Mor1 (the opposite numbering system from that used with the mitochondrial and cytosolic isozymes in the human). Ball et al. (1994) induced a mutant Mor2 allele and used it to map the gene to mouse chromosome 11 in a region of homology with human chromosome 2 by linkage analysis.GENE FUNCTION
Zhao et al. (2010) showed that lysine acetylation is a prevalent modification in enzymes that catalyze intermediate metabolism in the human liver. Virtually every enzyme in glycolysis, gluconeogenesis, the tricarboxylic acid (TCA) cycle, the urea cycle, fatty acid metabolism, and glycogen metabolism was found to be acetylated in human liver tissue. The concentration of metabolic fuels, such as glucose, amino acids, and fatty acids, influenced the acetylation status of metabolic enzymes. Acetylation activated enoyl-coenzyme A hydratase/3-hydroxyacyl-coenzyme A dehydrogenase (607037) in fatty acid oxidation and malate dehydrogenase in the TCA cycle, inhibited argininosuccinate lyase (608310) in the urea cycle, and destabilized phosphoenolpyruvate carboxykinase (261680) in gluconeogenesis. Zhao et al. (2010) concluded that acetylation plays a major role in metabolic regulation.EVOLUTION
Mitochondrial and soluble MDHs agree with the rule that the 2 forms of enzymes are coded by different chromosomes. However, Birktoft et al. (1982) found close structural homology of the 2 (as well as lactate dehydrogenase, see 150000) and concluded that they were derived from a common ancestral gene.MOLECULAR GENETICS
Davidson and Cortner (1967) observed an inherited variant of supernatant malate dehydrogenase of erythrocytes. The variant was found in a black woman and her 2 sons during a survey of 1470 blacks and 1440 whites. The electrophoretic nature of the variant suggested that the molecule is a dimer with mutation in the gene controlling one of the elements and that this gene is autosomal.HISTORY
Larson et al. (1982) mapped MDH1 to 2p23 by gene dosage. Friedrich et al. (1988) presented evidence from several nonhuman species and from humans that alpha-keto acid reductase (107920) and cytoplasmic malate dehydrogenase are identical. Friedrich et ... More on the omim web site
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
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 154200 was added.