MDH2/YOL126C Summary Help

Standard Name MDH2
Systematic Name YOL126C
Feature Type ORF, Verified
Description Cytoplasmic malate dehydrogenase; one of three isozymes that catalyze interconversion of malate and oxaloacetate; involved in the glyoxylate cycle and gluconeogenesis during growth on two-carbon compounds; interacts with Pck1p and Fbp1 (1, 2, 3 and see Summary Paragraph)
Name Description Malate DeHydrogenase
Chromosomal Location
ChrXV:82920 to 81787 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All MDH2 GO evidence and references
  View Computational GO annotations for MDH2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 18 genes
Classical genetics
Large-scale survey
45 total interaction(s) for 38 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 11
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 4
  • Reconstituted Complex: 1
  • Two-hybrid: 6

Genetic Interactions
  • Dosage Rescue: 1
  • Negative Genetic: 4
  • Phenotypic Enhancement: 2
  • Positive Genetic: 8
  • Synthetic Growth Defect: 3
  • Synthetic Lethality: 1
  • Synthetic Rescue: 1

Expression Summary
Length (a.a.) 377
Molecular Weight (Da) 40,730
Isoelectric Point (pI) 6.89
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXV:82920 to 81787 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2006-10-06 | Sequence: 2006-10-06
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1134 82920..81787 2006-10-06 2006-10-06
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000005486

Gluconeogenesis is the process whereby glucose is synthesized from non-carbohydrate precursors, which enables yeast cells to grow on non-sugar carbon sources like ethanol, glycerol, or peptone. The reactions of gluconeogenesis, shown here, mediate conversion of pyruvate to glucose, which is the opposite of glycolysis, the formation of pyruvate from glucose. While these two pathways have several reactions in common, they are not the exact reverse of each other. As the glycolytic enzymes phosphofructokinase (Pfk1p, Pfk2p) and pyruvate kinase (Cdc19p) only function in the forward direction, the gluconeogenesis pathway replaces those steps with the enzymes pyruvate carboxylase (Pyc1p, Pyc2p) and phosphoenolpyruvate carboxykinase (Pck1p)-generating oxaloacetate as an intermediate from pyruvate to phosphoenolpyruvate-and also the enzyme fructose-1,6-bisphosphatase (Fbp1p) (reviewed in 4). Overall, the gluconeogenic reactions convert two molecules of pyruvate to a molecule of glucose, with the expenditure of six high-energy phosphate bonds, four from ATP and two from GTP. Expression of genes encoding several of the gluconeogenic enzymes is subject to glucose repression (5).

MDH2 encodes cytosolic malate dehydrogenase, which generates oxaloacetate for glucose synthesis during gluconeogenesis. As such, Mdh2p is required for growth on minimal medium with ethanol or acetate as the carbon source (1). There are two other malate dehydrogenase isozymes: Mdh1p localizes to mitochondria and functions in the TCA cycle, and Mdh3p is in the peroxisome and is thought to catalyze a step in the glyoxylate pathway (reviewed in 3).

Levels of Mdh2p are regulated by glucose represssion of transcription and also by protein degradation when glucose-starved cells are replenished with glucose (6). Mdh2p is phosphorylated during the process of degradation, and both phosphorylation and degradation require a 12-residue amino-terminal extension not found in Mdh1p and Mdh3p (7, 8). There appear to be two pathways for degradation of Mdh2p: a proteasomal pathway that acts following short-term glucose starvation and a vacuolar pathway that functions following long-term glucose starvation (6). Mdh2p interacts with Pck1p and Fbp1p, which may facilitate flux through the gluconeogenic pathway, given the unfavorable equilibrium for formation of oxaloacetate from malate (3).

Last updated: 2005-06-23 Contact SGD

References cited on this page View Complete Literature Guide for MDH2
1) Minard KI and McAlister-Henn L  (1991) Isolation, nucleotide sequence analysis, and disruption of the MDH2 gene from Saccharomyces cerevisiae: evidence for three isozymes of yeast malate dehydrogenase. Mol Cell Biol 11(1):370-80
2) Lorenz MC and Fink GR  (2001) The glyoxylate cycle is required for fungal virulence. Nature 412(6842):83-6
3) Gibson N and McAlister-Henn L  (2003) Physical and genetic interactions of cytosolic malate dehydrogenase with other gluconeogenic enzymes. J Biol Chem 278(28):25628-36
4) Klein CJ, et al.  (1998) Glucose control in Saccharomyces cerevisiae: the role of Mig1 in metabolic functions. Microbiology 144 ( Pt 1)():13-24
5) Haarasilta S and Oura E  (1975) On the activity and regulation of anaplerotic and gluconeogenetic enzymes during the growth process of baker's yeast. The biphasic growth. Eur J Biochem 52(1):1-7
6) Hung GC, et al.  (2004) Degradation of the gluconeogenic enzymes fructose-1,6-bisphosphatase and malate dehydrogenase is mediated by distinct proteolytic pathways and signaling events. J Biol Chem 279(47):49138-50
7) Minard KI and McAlister-Henn L  (1994) Glucose-induced phosphorylation of the MDH2 isozyme of malate dehydrogenase in Saccharomyces cerevisiae. Arch Biochem Biophys 315(2):302-9
8) Minard KI and McAlister-Henn L  (1992) Glucose-induced degradation of the MDH2 isozyme of malate dehydrogenase in yeast. J Biol Chem 267(24):17458-64