PUT2/YHR037W Summary Help

Standard Name PUT2 1
Systematic Name YHR037W
Feature Type ORF, Verified
Description Delta-1-pyrroline-5-carboxylate dehydrogenase; nuclear-encoded mitochondrial protein involved in utilization of proline as sole nitrogen source; deficiency of the human homolog causes HPII, an autosomal recessive inborn error of metabolism (2, 3 and see Summary Paragraph)
Name Description Proline UTilization 1
Chromosomal Location
ChrVIII:181977 to 183704 | ORF Map | GBrowse
Gbrowse
Genetic position: 24 cM
Gene Ontology Annotations All PUT2 GO evidence and references
  View Computational GO annotations for PUT2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 5 genes
Resources
Pathways
Classical genetics
null
Large-scale survey
null
Resources
26 total interaction(s) for 23 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 3
  • Affinity Capture-RNA: 3
  • Co-crystal Structure: 1
  • Two-hybrid: 1

Genetic Interactions
  • Negative Genetic: 11
  • Phenotypic Suppression: 2
  • Positive Genetic: 3
  • Synthetic Growth Defect: 2

Resources
Expression Summary
histogram
Resources
Length (a.a.) 575
Molecular Weight (Da) 64,435
Isoelectric Point (pI) 6.99
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVIII:181977 to 183704 | ORF Map | GBrowse
SGD ORF map
Genetic position: 24 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1728 181977..183704 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 SGDIDS000001079
SUMMARY PARAGRAPH for PUT2

Proline is an amino acid that is not only required for protein synthesis but can also serve as a nitrogen source. Although proline is the least-preferred nitrogen source for many lab strains of S. cerevisiae, it is the most abundant source of nitrogen in grapes, the natural environment of wild yeast (4). When more optimal sources of nitrogen are unavailable, S. cerevisiae cells degrade proline into glutamate via the proline utilization pathway, shown here (1, 5). In the mitochondria, proline is first converted into delta-1-pyrroline-5-carboxylate (P5C) by the PUT1 gene product, proline oxidase (EC 1.5.99.8). Then, P5C is processed by the delta-1-pyrroline-5-carboxylate dehydrogenase (EC 1.5.1.12) Put2p into glutamate (1).

PUT1 and PUT2 are both nuclear genes that are positively regulated by the transcriptional activator Put3p (5). Although Put3p is bound constitutively to the promoters of PUT1 and PUT2, transcriptional upregulation only occurs in the presence of proline and the absence of a preferred nitrogen source (4, 6). In the absence of Put3p, the transcription factor Gal4p can bind at the Put3p binding site and upregulate PUT2 expression (7). PUT1 and PUT2 are also subject to regulation by nitrogen catabolite repression (NCR) (8, 9), which prevents the utilization of proline as a nitrogen source if better nitrogen compounds such as ammonia, asparagine or glutamine are present. PUT2 downregulation by NCR is mediated by the transcription factors Ure2p and Dal80p (9, 10). Independent of NCR, PUT2 expression is repressed by the global transcription factor Spt10p that acts by binding to a TATA element in the PUT2 promoter (11).

During anaerobic respiration, put2 mutations that remove a mitochondrial targeting sequence can enhance cell growth by improving anaerobic arginine catabolism (12). Conversely, under aerobic conditions put2 mutations lead to cell toxicity due to the accumulation of P5C and reactive oxygen species (13). Proline toxicity has also been observed upon mutation of the Arabidopsis ortholog P5CDH (14). In humans, mutation of the PUT2 ortholog, ALDH4A1 (OMIM), causes the genetic disease type II hyperprolinemia (OMIM) which is characterized by elevated levels of P5C, mental retardation, and convulsions (15).

Last updated: 2005-09-07 Contact SGD

References cited on this page View Complete Literature Guide for PUT2
1) 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
2) Brandriss MC  (1983) Proline utilization in Saccharomyces cerevisiae: analysis of the cloned PUT2 gene. Mol Cell Biol 3(10):1846-56
3) Hu CA, et al.  (1996) Cloning, characterization, and expression of cDNAs encoding human delta 1-pyrroline-5-carboxylate dehydrogenase. J Biol Chem 271(16):9795-800
4) Huang HL and Brandriss MC  (2000) The regulator of the yeast proline utilization pathway is differentially phosphorylated in response to the quality of the nitrogen source. Mol Cell Biol 20(3):892-9
5) Brandriss MC and Magasanik B  (1979) Genetics and physiology of proline utilization in Saccharomyces cerevisiae: mutation causing constitutive enzyme expression. J Bacteriol 140(2):504-7
6) Axelrod JD, et al.  (1991) Proline-independent binding of PUT3 transcriptional activator protein detected by footprinting in vivo. Mol Cell Biol 11(1):564-7
7) D'Alessio M and Brandriss MC  (2000) Cross-pathway regulation in Saccharomyces cerevisiae: activation of the proline utilization pathway by Ga14p in vivo. J Bacteriol 182(13):3748-53
8) 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
9) 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
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) Yamashita I  (1993) Isolation and characterization of the SUD1 gene, which encodes a global repressor of core promoter activity in Saccharomyces cerevisiae. Mol Gen Genet 241(5-6):616-26
12) Martin O, et al.  (2003) Improved anaerobic use of arginine by Saccharomyces cerevisiae. Appl Environ Microbiol 69(3):1623-8
13) Nomura M and Takagi H  (2004) Role of the yeast acetyltransferase Mpr1 in oxidative stress: regulation of oxygen reactive species caused by a toxic proline catabolism intermediate. Proc Natl Acad Sci U S A 101(34):12616-21
14) Deuschle K, et al.  (2001) A nuclear gene encoding mitochondrial Delta-pyrroline-5-carboxylate dehydrogenase and its potential role in protection from proline toxicity. Plant J 27(4):345-56
15) Geraghty MT, et al.  (1998) Mutations in the Delta1-pyrroline 5-carboxylate dehydrogenase gene cause type II hyperprolinemia. Hum Mol Genet 7(9):1411-5