CAR1/YPL111W Summary Help

Standard Name CAR1 1
Systematic Name YPL111W
Alias LPH15
Feature Type ORF, Verified
Description Arginase, catabolizes arginine to ornithine and urea; expression responds to both induction by arginine and nitrogen catabolite repression; disruption decreases production of carcinogen ethyl carbamate during wine fermentation and also enhances freeze tolerance (2, 3, 4, 5, 6 and see Summary Paragraph)
Also known as: cargA 7 , 8
Name Description Catabolism of ARginine
Chromosomal Location
ChrXVI:339944 to 340945 | ORF Map | GBrowse
Genetic position: -75 cM
Gene Ontology Annotations All CAR1 GO evidence and references
  View Computational GO annotations for CAR1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 20 genes
Classical genetics
Large-scale survey
22 total interaction(s) for 18 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 11
  • Affinity Capture-RNA: 1
  • PCA: 3
  • Reconstituted Complex: 1
  • Two-hybrid: 5

Genetic Interactions
  • Positive Genetic: 1

Expression Summary
Length (a.a.) 333
Molecular Weight (Da) 35,662
Isoelectric Point (pI) 5.44
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXVI:339944 to 340945 | ORF Map | GBrowse
Genetic position: -75 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1002 339944..340945 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 SGDIDS000006032

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 to form urea and ornithine (9). Ornithine is then transaminated by the Car2p ornithine amino transferase (EC into L-glutamate gamma-semialdehyde (9), which in turn spontaneously forms L-delta-1-pyrroline-5-carboxylate (p5c). Subsequently, p5c is converted into proline by the p5c reductase (EC Pro3p (10). In the absence of oxygen arginine degradation does not proceed further and the pathway is as shown here (11). If oxygen is present, proline is converted to glutamate via the proline utilization pathway (shown here) in the mitochondria (12, 13).

Car1p forms a homotrimer (14) that requires Mn2+ ion binding for activity and tertiary stability and Zn2+ ion binding for tertiary and quaternary stability (15). Car1p also forms a one-to-one multienzyme complex with Arg3p, an enzyme involved in arginine biosynthesis (15). In the presence of arginine, Car1p is able to inhibit Arg3p activity (16).

The regulation of CAR1 expression is complex, as the CAR1 promoter region contains one upstream repression site (URS) and four upstream activation sites (UAS) (17). The URS is bound by the global repressor Ume6p, which forms a complex with Sin3p and Rpd3p that downregulates CAR1 expression (18). This repression is opposed by the global transcriptional activators Abf1p and Rap1p that bind two of the four UASs (19, 20). The balance between positive and negative control by these global transcription factors is tipped toward induction when arginine is present and towards repression when it is not. The presence of arginine also induces the binding of the transcription factors Arg80p, Arg81p, and Mcm1p at the third UAS (21, 22). CAR1 is also subject to nitrogen catabolite repression (NCR) (23), which is mediated by the negative regulator Ure2p (24, 25). In the presence of arginine and the absence of a preferred nitrogen source NCR is released, and the GATA transcriptional activators Gln3p and Gat1p bind to the fourth UAS, upregulating CAR1 expression (21, 24, 17).

When cells are starved for nitrogen, car1 mutations result in increased levels of arginine and/or glutamate, cell growth arrest, and accumulation in the unbudded G1 phase (26). Loss of CAR1 has also been shown to have industrial benefits, as car1 mutants display reduced levels of the carcinogen ethyl carbamate in wine and sake (27) and show enhanced freeze tolerance, resulting in increased leavening ability during the frozen dough baking process (5). Mutations in the human homolog ARG1 (OMIM) lead to the autosomal recessive genetic disease argininemia (OMIM); the clinical features include growth and mental retardation, microcephaly, and spasticity (28, 29, 30).

Last updated: 2005-09-14 Contact SGD

References cited on this page View Complete Literature Guide for CAR1
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) Sumrada RA and Cooper TG  (1987) Ubiquitous upstream repression sequences control activation of the inducible arginase gene in yeast. Proc Natl Acad Sci U S A 84(12):3997-4001
3) Kovari L, et al.  (1990) Multiple positive and negative cis-acting elements mediate induced arginase (CAR1) gene expression in Saccharomyces cerevisiae. Mol Cell Biol 10(10):5087-97
4) Bossinger J and Cooper TG  (1977) Molecular events associated with induction of arginase in Saccharomyces cerevisiae. J Bacteriol 131(1):163-73
5) Shima J, et al.  (2003) Disruption of the CAR1 gene encoding arginase enhances freeze tolerance of the commercial baker's yeast Saccharomyces cerevisiae. Appl Environ Microbiol 69(1):715-8
6) Wu D, et al.  (2014) Decreased ethyl carbamate generation during Chinese rice wine fermentation by disruption of CAR1 in an industrial yeast strain. Int J Food Microbiol 180():19-23
7) Dubois E, et al.  (1982) Expression of the ROAM mutations in Saccharomyces cerevisiae: involvement of trans-acting regulatory elements and relation with the Ty1 transcription. EMBO J 1(9):1133-9
8) 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
9) Middelhoven WJ  (1964) THE PATHWAY OF ARGININE BREAKDOWN IN SACCHAROMYCES CEREVISIAE. Biochim Biophys Acta 93():650-2
10) 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
11) Martin O, et al.  (2003) Improved anaerobic use of arginine by Saccharomyces cerevisiae. Appl Environ Microbiol 69(3):1623-8
12) Brandriss MC and Magasanik B  (1980) Proline: an essential intermediate in arginine degradation in Saccharomyces cerevisiae. J Bacteriol 143(3):1403-10
13) 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
14) Penninckx M, et al.  (1974) Interaction between arginase and L-ornithine carbamoyltransferase in Saccharomyces cerevisiae. Purification of S. cerevisiae enzymes and evidence that these enzymes as well as rat-liver arginase are trimers. Eur J Biochem 49(2):429-42
15) Green SM, et al.  (1991) Roles of metal ions in the maintenance of the tertiary and quaternary structure of arginase from Saccharomyces cerevisiae. J Biol Chem 266(32):21474-81
16) Penninckx M  (1975) Interaction between arginase and L-ornithine carbamoyltransferase in Saccharomyces cerevisiae. The regulatory sites of arginase. Eur J Biochem 58(2):533-8
17) Smart WC, et al.  (1996) Combinatorial regulation of the Saccharomyces cerevisiae CAR1 (arginase) promoter in response to multiple environmental signals. Mol Cell Biol 16(10):5876-87
18) 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
19) Kovari LZ and Cooper TG  (1991) Participation of ABF-1 protein in expression of the Saccharomyces cerevisiae CAR1 gene. J Bacteriol 173(20):6332-8
20) Kovari LZ, et al.  (1993) Participation of RAP1 protein in expression of the Saccharomyces cerevisiae arginase (CAR1) gene. J Bacteriol 175(4):941-51
21) Dubois E and Messenguy F  (1997) Integration of the multiple controls regulating the expression of the arginase gene CAR1 of Saccharomyces cerevisiae in response to differentnitrogen signals: role of Gln3p, ArgRp-Mcm1p, and Ume6p. Mol Gen Genet 253(5):568-80
22) 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
23) ter Schure EG, et al.  (2000) The role of ammonia metabolism in nitrogen catabolite repression in Saccharomyces cerevisiae. FEMS Microbiol Rev 24(1):67-83
24) Coffman JA, et al.  (1996) Gat1p, a GATA family protein whose production is sensitive to nitrogen catabolite repression, participates in transcriptional activation of nitrogen-catabolic genes in Saccharomyces cerevisiae. Mol Cell Biol 16(3):847-58
25) Xu S, et al.  (1995) Roles of URE2 and GLN3 in the proline utilization pathway in Saccharomyces cerevisiae. Mol Cell Biol 15(4):2321-30
26) Cooper TG, et al.  (1979) Addition of basic amino acids prevents G-1 arrest of nitrogen-starved cultures of Saccharomyces cerevisiae. J Bacteriol 137(3):1447-8
27) Kitamoto K, et al.  (1991) Genetic engineering of a sake yeast producing no urea by successive disruption of arginase gene. Appl Environ Microbiol 57(1):301-6
28) Cederbaum SD, et al.  (1977) Hyperargininemia. J Pediatr 90(4):569-73
29) Michels VV and Beaudet AL  (1978) Arginase deficiency in multiple tissues in argininemia. Clin Genet 13(1):61-7
30) Terheggen HG, et al.  (1972) Familial hyperargininemia. J Genet Hum 20(1):69-84