GDH2/YDL215C Summary Help

Standard Name GDH2
Systematic Name YDL215C
Feature Type ORF, Verified
Description NAD(+)-dependent glutamate dehydrogenase; degrades glutamate to ammonia and alpha-ketoglutarate; expression sensitive to nitrogen catabolite repression and intracellular ammonia levels; genetically interacts with GDH3 by suppressing stress-induced apoptosis (1, 2, 3, 4 and see Summary Paragraph)
Also known as: GDH-B 5 , GDHB
Name Description Glutamate DeHydrogenase
Chromosomal Location
ChrIV:73918 to 70640 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All GDH2 GO evidence and references
  View Computational GO annotations for GDH2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Regulators 11 genes
Classical genetics
Large-scale survey
114 total interaction(s) for 96 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 14
  • Affinity Capture-Western: 1
  • Biochemical Activity: 1
  • PCA: 3
  • Two-hybrid: 2

Genetic Interactions
  • Dosage Rescue: 2
  • Negative Genetic: 75
  • Phenotypic Suppression: 1
  • Positive Genetic: 12
  • Synthetic Growth Defect: 3

Expression Summary
Length (a.a.) 1,092
Molecular Weight (Da) 124,331
Isoelectric Point (pI) 5.52
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrIV:73918 to 70640 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..3279 73918..70640 2011-02-03 1996-07-31
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 SGDIDS000002374

In S. cerevisiae cells, the amino group of glutamate and the amide group of glutamine are the source of nitrogen for biosynthesis of all other macromolecules (1). In order to provide ammonia for the synthesis of glutamine during growth on glutamate-yielding nitrogen sources, cells degrade glutamate into ammonia and oxaloacetate. The main pathway for S cerevisiae glutamate degradation, shown here, is catalyzed by the NAD-dependent glutamate dehydrogenase encoded by GDH2 (1).

Transcriptional regulation of GDH2 is dependent upon six different sequence elements present in the promoter (6). Two elements behave as upstream activation sites (UAS) while the remaining four elements inhibit the effects of the two UASs (6). These upstream repression site (URS) elements bear significant sequence similarity to the URS found in the CAR1 promoter, which is bound by the global repressor Ume6p (6, 7). One UAS has been shown to activate transcription during growth on nonfermentable carbon sources or on limiting amounts of glucose (8). The other UAS, UASNTR, is under the control of nitrogen catabolite repression (NCR) (9). Under nitrogen-poor conditions, GDH2 expression is upregulated by the transcriptional activator Gln3p, which binds to the UASNTR, and the co-activator Hfi1p, which links Gln3p to the Ada2/Gcn5/Ada3 transcriptional activator complex (10, 11). Conversely, in the presence of an optimal nitrogen source such as glutamine, GDH2 transcription is repressed by sequestration of Gln3p to the cytosol by the transcription factor Ure2p (12). Unrelated to NCR, GDH2 gene expression is regulated by ammonia concentration. An increase in intracellular ammonia leads to a decrease in GDH2 expression (3) but an increase in extracellular ammonia leads to an increase in both GDH2 transcription and Gdh2p activity (13). Gdh2p enzyme activity also appears to be regulated by phosphorylation through cAMP-dependent and cAMP-independent protein kinases and subsequent proteolysis (14, 15).

Loss of Gdh2p leads to impaired glutamate utilization and severely reduced growth on poor nitrogen sources (1). Although Gdh2p is not normally involved in glutamate biosynthesis, overexpression of GDH2 can promote catalysis of the reverse reaction (1). Overexpression of GDH2 also suppresses the phenotype of cells lacking the phosphoglucose isomerase Pgi1p, which cannot grow on glucose as the sole carbon source (16). Deficiencies in the human homologs of glutamate dehydrogenase, GLUD1 (OMIM) and GLUD2 (OMIM), have been linked to hyperinsulinism-hyperammonemia syndrome (OMIM) (17, 18) and various neurological disorders (19).

Last updated: 2005-10-11 Contact SGD

References cited on this page View Complete Literature Guide for GDH2
1) Miller SM and Magasanik B  (1990) Role of NAD-linked glutamate dehydrogenase in nitrogen metabolism in Saccharomyces cerevisiae. J Bacteriol 172(9):4927-35
2) DeLuna A, et al.  (2001) NADP-glutamate dehydrogenase isoenzymes of Saccharomyces cerevisiae. Purification, kinetic properties, and physiological roles. J Biol Chem 276(47):43775-83
3) Tate JJ and Cooper TG  (2003) Tor1/2 regulation of retrograde gene expression in Saccharomyces cerevisiae derives indirectly as a consequence of alterations in ammonia metabolism. J Biol Chem 278(38):36924-33
4) Lee YJ, et al.  (2012) Involvement of GDH3-encoded NADP+-dependent glutamate dehydrogenase in yeast cell resistance to stress-induced apoptosis in stationary phase cells. J Biol Chem 287(53):44221-33
5) Middelhoven WJ, et al.  (1978) A mutant of Saccharomyces cerevisiae lacking catabolic NAD-specific glutamate dehydrogenase. Growth characteristics of the mutant and regulation of enzyme synthesis in the wild-type strain. Antonie Van Leeuwenhoek 44(3-4):311-20
6) Miller SM and Magasanik B  (1991) Role of the complex upstream region of the GDH2 gene in nitrogen regulation of the NAD-linked glutamate dehydrogenase in Saccharomyces cerevisiae. Mol Cell Biol 11(12):6229-47
7) Messenguy F, et al.  (2000) In Saccharomyces cerevisiae, expression of arginine catabolic genes CAR1 and CAR2 in response to exogenous nitrogen availability is mediated by the Ume6 (CargRI)-Sin3 (CargRII)-Rpd3 (CargRIII) complex. J Bacteriol 182(11):3158-64
8) Coschigano PW, et al.  (1991) Physiological and genetic analysis of the carbon regulation of the NAD-dependent glutamate dehydrogenase of Saccharomyces cerevisiae. Mol Cell Biol 11(9):4455-65
9) Nunez de Castro I, et al.  (1970) Effect of glucose, galactose, and different nitrogen-sources on the activity of yeast glutamate dehydrogenase (NAD and NADP-linked) from normal strain and impaired respiration mutant. Eur J Biochem 16(3):567-70
10) Daugherty JR, et al.  (1993) Regulatory circuit for responses of nitrogen catabolic gene expression to the GLN3 and DAL80 proteins and nitrogen catabolite repression in Saccharomyces cerevisiae. J Bacteriol 175(1):64-73
11) Soussi-Boudekou S and Andre B  (1999) A co-activator of nitrogen-regulated transcription in Saccharomyces cerevisiae. Mol Microbiol 31(3):753-62
12) Coschigano PW and Magasanik B  (1991) The URE2 gene product of Saccharomyces cerevisiae plays an important role in the cellular response to the nitrogen source and has homology to glutathione s-transferases. Mol Cell Biol 11(2):822-32
13) ter Schure EG, et al.  (1995) The concentration of ammonia regulates nitrogen metabolism in Saccharomyces cerevisiae. J Bacteriol 177(22):6672-5
14) Uno I, et al.  (1984) Regulation of NAD-dependent glutamate dehydrogenase by protein kinases in Saccharomyces cerevisiae. J Biol Chem 259(2):1288-93
15) Hemmings BA  (1980) Phosphorylation and proteolysis regulate the NAD-dependent glutamate dehydrogenase from Saccharomyces cerevisiae. FEBS Lett 122(2):297-302
16) Boles E, et al.  (1993) The role of the NAD-dependent glutamate dehydrogenase in restoring growth on glucose of a Saccharomyces cerevisiae phosphoglucose isomerase mutant. Eur J Biochem 217(1):469-77
17) Stanley CA, et al.  (1998) Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. N Engl J Med 338(19):1352-7
18) MacMullen C, et al.  (2001) Hyperinsulinism/hyperammonemia syndrome in children with regulatory mutations in the inhibitory guanosine triphosphate-binding domain of glutamate dehydrogenase. J Clin Endocrinol Metab 86(4):1782-7
19) Plaitakis A, et al.  (1984) Neurological disorders associated with deficiency of glutamate dehydrogenase. Ann Neurol 15(2):144-53