UGA2/YBR006W Summary Help

Standard Name UGA2 1
Systematic Name YBR006W
Alias UGA5 2
Feature Type ORF, Verified
Description Succinate semialdehyde dehydrogenase; involved in the utilization of gamma-aminobutyrate (GABA) as a nitrogen source; part of the 4-aminobutyrate and glutamate degradation pathways; localized to the cytoplasm (1, 3 and see Summary Paragraph)
Name Description Utilization of GAba 1
Chromosomal Location
ChrII:247010 to 248503 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All UGA2 GO evidence and references
  View Computational GO annotations for UGA2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
High-throughput
Regulators 5 genes
Resources
Pathways
Classical genetics
null
Large-scale survey
null
Resources
27 total interaction(s) for 20 unique genes/features.
Physical Interactions
  • Affinity Capture-RNA: 1
  • PCA: 3
  • Two-hybrid: 3

Genetic Interactions
  • Dosage Lethality: 1
  • Negative Genetic: 6
  • Phenotypic Enhancement: 2
  • Positive Genetic: 2
  • Synthetic Growth Defect: 6
  • Synthetic Lethality: 2
  • Synthetic Rescue: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 497
Molecular Weight (Da) 54,189
Isoelectric Point (pI) 6.61
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrII:247010 to 248503 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1999-04-26
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1494 247010..248503 2011-02-03 1999-04-26
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000000210
SUMMARY PARAGRAPH for UGA2

In S. cerevisiae the non-protein amino acid gamma-aminobutyric acid (GABA) plays a role in nitrogen utilization and oxidative stress tolerance (2, 1). GABA accumulation occurs through permease-mediated uptake by Uga4p, Put4p, and Gap1p, or intracellular production via glutamate degradation by the glutamate decarboxylase Gad1p (4 and references therein). GABA degradation into succinate is a two-step process mediated by the gene products of UGA1 and UGA2. UGA1 encodes a 4-aminobutyrate aminotransferase that deaminates GABA to succinate semialdehyde which in turn is converted to succinate by the succinate semialdehyde dehydrogenase (SSADH) encoded by UGA2 (1). S. cerevisiae cells in which GABA degradation is blocked are more sensitive to oxidative stress and can no longer grow on GABA as their sole nitrogen source (2, 1).

The presence of GABA causes an increase in expression of UGA1 and UGA2 which is mediated by the transcriptional activators Uga3p, Dal81p, and Gln3p (1, 5, 6, 2). Uga3p and Dal81p bind to upstream activation sites called the UAS-GABA element found in the promoters of GABA regulated genes. (7, 5). Gln3p is involved in a more general nitrogen regulation of transcription through binding of the promoter element UAS-GATA (2 and references therein). Levels of UGA2 transcript are also upregulated under conditions of oxidative stress (2).

UGA2 shares sequence similarity with SSADH enzymes from bacteria, plants, and humans (2). Mutations in the human SSADH gene, ALDH5A1 (OMIM), have been associated with the disease succinic semialdehyde dehydrogenase deficiency (OMIM), the clinical features of which include developmental and neurological abnormalities.

About glutamate degradation

In S. cerevisiae, the main pathway for glutamate degradation is catalyzed by the glutamate dehydrogenase encoded by GDH2 (8). However, glutamate can also by degraded into gamma-aminobutyrate (GABA) by the glutamate decarboxylase Gad1p and then converted into succinate by the enzymes encoded by UGA1 and UGA2 (2). Glutamate degradation by this pathway and expression of its genes have been shown to be important for oxidative stress tolerance. Conditions of oxidative stress elevate the transcript levels of GAD1 and UGA2 (2). UGA1 and UGA2 expression is also upregulated in the presence of GABA which is mediated by the transcriptional activators Uga3p and Uga35p/Dal81p (1), 5). These transcription factors bind to upstream activation sites in the promoters of GABA-regulated genes known as the UAS-GABA (7, 5). Regulation of Gad1p is suggested to be linked to calcium levels as the protein is able to bind calmodulin (2). S. cerevisiae cells in which this pathway is blocked are more sensitive to oxidative stress and can no longer grow on GABA as their sole nitrogen source (2, 1).

Last updated: 2007-05-25 Contact SGD

References cited on this page View Complete Literature Guide for UGA2
1) Ramos F, et al.  (1985) Mutations affecting the enzymes involved in the utilization of 4-aminobutyric acid as nitrogen source by the yeast Saccharomyces cerevisiae. Eur J Biochem 149(2):401-4
2) Coleman ST, et al.  (2001) Expression of a glutamate decarboxylase homologue is required for normal oxidative stress tolerance in Saccharomyces cerevisiae. J Biol Chem 276(1):244-50
3) Huh WK, et al.  (2003) Global analysis of protein localization in budding yeast. Nature 425(6959):686-91
4) Andre B, et al.  (1993) Cloning and expression of the UGA4 gene coding for the inducible GABA-specific transport protein of Saccharomyces cerevisiae. Mol Gen Genet 237(1-2):17-25
5) Vissers S, et al.  (1989) Positive and negative regulatory elements control the expression of the UGA4 gene coding for the inducible 4-aminobutyric-acid-specific permease in Saccharomyces cerevisiae. Eur J Biochem 181(2):357-61
6) Talibi D, et al.  (1995) Cis- and trans-acting elements determining induction of the genes of the gamma-aminobutyrate (GABA) utilization pathway in Saccharomyces cerevisiae. Nucleic Acids Res 23(4):550-7
7) Idicula AM, et al.  (2002) Binding and activation by the zinc cluster transcription factors of Saccharomyces cerevisiae. Redefining the UASGABA and its interaction with Uga3p. J Biol Chem 277(48):45977-83
8) Miller SM and Magasanik B  (1990) Role of NAD-linked glutamate dehydrogenase in nitrogen metabolism in Saccharomyces cerevisiae. J Bacteriol 172(9):4927-35