PRO1/YDR300C Summary Help

Standard Name PRO1 1
Systematic Name YDR300C
Feature Type ORF, Verified
Description Gamma-glutamyl kinase; catalyzes the first step in proline biosynthesis; PRO1 has a paralog, YHR033W, that arose from the whole genome duplication (2, 3, 4 and see Summary Paragraph)
Name Description PROline requiring
Chromosomal Location
ChrIV:1062791 to 1061505 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: 187 cM
Gene Ontology Annotations All PRO1 GO evidence and references
  View Computational GO annotations for PRO1
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
36 total interaction(s) for 29 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 16
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 1
  • Co-purification: 1
  • PCA: 2
  • Two-hybrid: 2

Genetic Interactions
  • Dosage Rescue: 2
  • Phenotypic Enhancement: 1
  • Synthetic Growth Defect: 2
  • Synthetic Lethality: 7

Resources
Expression Summary
histogram
Resources
Length (a.a.) 428
Molecular Weight (Da) 47,162
Isoelectric Point (pI) 6.75
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIV:1062791 to 1061505 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: 187 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1287 1062791..1061505 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 SGDIDS000002708
SUMMARY PARAGRAPH for PRO1

Proline is a member of the glutamine family of amino acids, whose biosynthesis depends on the carbon skeleton of glutamic acid. Proline biosynthesis, shown here, occurs in the cytosol and begins with activation of glutamate, by the Pro1p gamma-glutamyl kinase (EC 2.7.2.11), to form glutamate-5-phosphate (5, 3). This unstable intermediate is subsequently converted to glutamate semialdehyde by the gamma-glutamyl phosphate reductase (EC 1.2.1.41) Pro2p (5, 3). Glutamate semialdehyde spontaneously cyclizes to form delta 1-pyrroline-5-carboxylate (P5C) (5), which is then converted to proline by Pro3p, a P5C reductase (EC 1.5.1.2) (5, 6). In S. cerevisiae, the P5C reductase enzyme also catalyzes the fourth step in arginine degradation (7). Since these two pathways converge at this step, the requirement for proline in pro1 and pro2 mutant cells can be satisfied by arginine. In contrast, pro3 mutants require the addition of proline for growth (3). A unique property of all the pro mutant strains is that they cannot grow on standard YPD rich media. (3).

Many of the genes involved in S. cerevisiae amino acid biosynthesis are coregulated by a process known as the general amino acid control system. In response to starvation for any single amino acid, the expression of many biosynthetic enzymes is upregulated (8, 9). Mutational studies suggest that PRO1 and PRO2 expression is regulated by general amino acid control mediated by the transcriptional activator Gcn4p (2). However, microarray expression profiling indicates that only PRO2 is a target of Gcn4p (10). This study also shows that PRO1 expression is repressed in response to histidine starvation imposed by 3-aminotriazole (10).

In humans, the activities of Pro1p and Pro2p reside in a single enzyme, the delta 1-pyrroline-5-carboxylate synthetase ALDH18A1 (11). Mutations in this gene lead to hyperammonemia, hypoornithinemia, hypocitrullinemia, hypoargininemia, and hypoprolinemia and may be associated with neurodegeneration, cataracts, and connective tissue diseases (OMIM) (11).

Last updated: 2005-09-21 Contact SGD

References cited on this page View Complete Literature Guide for PRO1
1) Brandriss, M.  (1989) Personal Communication, Mortimer Map Edition 10
2) Li W and Brandriss MC  (1992) Proline biosynthesis in Saccharomyces cerevisiae: molecular analysis of the PRO1 gene, which encodes gamma-glutamyl kinase. J Bacteriol 174(12):4148-56
3) Tomenchok DM and Brandriss MC  (1987) Gene-enzyme relationships in the proline biosynthetic pathway of Saccharomyces cerevisiae. J Bacteriol 169(12):5364-72
4) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
5) Brandriss MC  (1979) Isolation and preliminary characterization of Saccharomyces cerevisiae proline auxotrophs. J Bacteriol 138(3):816-22
6) 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
7) Brandriss MC and Magasanik B  (1980) Proline: an essential intermediate in arginine degradation in Saccharomyces cerevisiae. J Bacteriol 143(3):1403-10
8) Hinnebusch AG  (1988) Mechanisms of gene regulation in the general control of amino acid biosynthesis in Saccharomyces cerevisiae. Microbiol Rev 52(2):248-73
9) Hinnebusch AG  (1986) The general control of amino acid biosynthetic genes in the yeast Saccharomyces cerevisiae. CRC Crit Rev Biochem 21(3):277-317
10) Natarajan K, et al.  (2001) Transcriptional profiling shows that Gcn4p is a master regulator of gene expression during amino acid starvation in yeast. Mol Cell Biol 21(13):4347-68
11) Aral B, et al.  (1996) Database cloning human delta 1-pyrroline-5-carboxylate synthetase (P5CS) cDNA: a bifunctional enzyme catalyzing the first 2 steps in proline biosynthesis. C R Acad Sci III 319(3):171-8