CAR2/YLR438W Summary Help

Standard Name CAR2 1
Systematic Name YLR438W
Feature Type ORF, Verified
Description L-ornithine transaminase (OTAse); catalyzes the second step of arginine degradation, expression is dually-regulated by allophanate induction and a specific arginine induction process; not nitrogen catabolite repression sensitive; protein abundance increases in response to DNA replication stress (1, 2, 3, 4 and see Summary Paragraph)
Also known as: cargB 1 , 5
Name Description Catabolism of ARginine
Chromosomal Location
ChrXII:1012501 to 1013775 | ORF Map | GBrowse
Gbrowse
Genetic position: 330 cM
Gene Ontology Annotations All CAR2 GO evidence and references
  View Computational GO annotations for CAR2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 26 genes
Resources
Pathways
Classical genetics
null
Large-scale survey
null
overexpression
Resources
50 total interaction(s) for 44 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 27
  • Affinity Capture-RNA: 1
  • Biochemical Activity: 2
  • Co-purification: 1
  • Reconstituted Complex: 2
  • Two-hybrid: 4

Genetic Interactions
  • Negative Genetic: 2
  • Positive Genetic: 5
  • Synthetic Growth Defect: 2
  • Synthetic Lethality: 4

Resources
Expression Summary
histogram
Resources
Length (a.a.) 424
Molecular Weight (Da) 46,086
Isoelectric Point (pI) 6.94
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXII:1012501 to 1013775 | ORF Map | GBrowse
SGD ORF map
Genetic position: 330 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1275 1012501..1013775 2011-02-03 1996-07-31
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 SGDIDS000004430
SUMMARY PARAGRAPH for CAR2

When optimal sources of nitrogen are unavailable, S. cerevisiae is able to utilize arginine as its sole nitrogen source. Arginine catabolism begins in the cytosol with the hydrolysis of arginine by the Car1p arginase (EC 3.5.3.1) to form urea and ornithine (6). Ornithine is then transaminated by the Car2p ornithine amino transferase (EC 2.6.1.13) into L-glutamate gamma-semialdehyde (6), which in turn spontaneously forms L-delta-1-pyrroline-5-carboxylate (p5c). Subsequently, p5c is converted into proline by the p5c reductase (EC 1.5.1.2) Pro3p (7). In the absence of oxygen arginine degradation does not proceed further and the pathway is as shown here (8). If oxygen is present, proline is converted to glutamate via the proline utilization pathway (shown here) in the mitochondria (9, 10).

CAR2 gene expression is regulated in a manner very similar to that of CAR1. An upstream repression site in the CAR2 promoter is bound by the global repressor Ume6p, which forms a complex with Sin3p and Rpd3p that downregulates CAR2 expression (11). This repression is balanced by binding of the global transcriptional activators Abf1p and Rap1p at an upstream activation site (2). The balance between positive and negative control by these global transcription factors is tipped toward induction when arginine is present and toward repression when it is not. The presence of arginine also induces the binding of the transcriptional activators Arg80p, Arg81p, and Mcm1p (12, 13, 14). The presence of allophanate, a degradation product of urea, increases CAR2 expression through the two positive regulators, Dal81p and Dal82p (2). Unlike many of the genes involved in arginine degradation, CAR2 is not sensitive to nitrogen catabolite repression (2).

S. cerevisiae cells deficient in Car2p are unable to grow on ornithine, and presumably arginine, as their sole nitrogen source (5). In humans, deficiency of the CAR2 homolog, ornithine-delta-aminotransferase, results in the progressive blinding disorder, gyrate atrophy of the choroid and retina (OMIM) (15).

Last updated: 2005-09-14 Contact SGD

References cited on this page View Complete Literature Guide for CAR2
1) Deschamps J and Wiame JM  (1979) Mating-type effect on cis mutations leading to constitutivity of ornithine transaminase in diploid cells of Saccharomyces cerevisiae. Genetics 92(3):749-58
2) Park HD, et al.  (1999) Synergistic operation of the CAR2 (Ornithine transaminase) promoter elements in Saccharomyces cerevisiae. J Bacteriol 181(22):7052-64
3) Degols G  (1987) Functional analysis of the regulatory region adjacent to the cargB gene of Saccharomyces cerevisiae. Nucleotide sequence, gene fusion experiments and cis-dominant regulatory mutation analysis. Eur J Biochem 169(1):193-200
4) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
5) Dubois E, et al.  (1978) Specific induction of catabolism and its relation to repression of biosynthesis in arginine metabolism of Saccharomyces cerevisiae. J Mol Biol 122(4):383-406
6) Middelhoven WJ  (1964) THE PATHWAY OF ARGININE BREAKDOWN IN SACCHAROMYCES CEREVISIAE. Biochim Biophys Acta 93():650-2
7) Brandriss MC and Falvey DA  (1992) Proline biosynthesis in Saccharomyces cerevisiae: analysis of the PRO3 gene, which encodes delta 1-pyrroline-5-carboxylate reductase. J Bacteriol 174(11):3782-8
8) Martin O, et al.  (2003) Improved anaerobic use of arginine by Saccharomyces cerevisiae. Appl Environ Microbiol 69(3):1623-8
9) Brandriss MC and Magasanik B  (1980) Proline: an essential intermediate in arginine degradation in Saccharomyces cerevisiae. J Bacteriol 143(3):1403-10
10) Brandriss MC and Magasanik B  (1979) Genetics and physiology of proline utilization in Saccharomyces cerevisiae: enzyme induction by proline. J Bacteriol 140(2):498-503
11) 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
12) Messenguy F, et al.  (1991) Determination of the DNA-binding sequences of ARGR proteins to arginine anabolic and catabolic promoters. Mol Cell Biol 11(5):2852-63
13) Dubois E, et al.  (2000) Inositol polyphosphate kinase activity of Arg82/ArgRIII is not required for the regulation of the arginine metabolism in yeast. FEBS Lett 486(3):300-4
14) Messenguy F and Dubois E  (1993) Genetic evidence for a role for MCM1 in the regulation of arginine metabolism in Saccharomyces cerevisiae. Mol Cell Biol 13(4):2586-92
15) Mitchell GA, et al.  (1988) An initiator codon mutation in ornithine-delta-aminotransferase causing gyrate atrophy of the choroid and retina. J Clin Invest 81(2):630-3