PUT1/YLR142W Summary Help

Standard Name PUT1 1
Systematic Name YLR142W
Feature Type ORF, Verified
Description Proline oxidase; nuclear-encoded mitochondrial protein involved in utilization of proline as sole nitrogen source; PUT1 transcription is induced by Put3p in the presence of proline and the absence of a preferred nitrogen source (2, 3 and see Summary Paragraph)
Name Description Proline UTilization 1
Chromosomal Location
ChrXII:425186 to 426616 | ORF Map | GBrowse
Gbrowse
Genetic position: 73 cM
Gene Ontology Annotations All PUT1 GO evidence and references
  View Computational GO annotations for PUT1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 9 genes
Resources
Pathways
Classical genetics
null
overexpression
Large-scale survey
null
Resources
17 total interaction(s) for 16 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 1

Genetic Interactions
  • Negative Genetic: 6
  • Phenotypic Suppression: 2
  • Positive Genetic: 1
  • Synthetic Growth Defect: 1
  • Synthetic Lethality: 5
  • Synthetic Rescue: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 476
Molecular Weight (Da) 53,271
Isoelectric Point (pI) 9.63
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXII:425186 to 426616 | ORF Map | GBrowse
SGD ORF map
Genetic position: 73 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1431 425186..426616 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 SGDIDS000004132
SUMMARY PARAGRAPH for PUT1

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 (2). When more optimal sources of nitrogen are unavailable, S. cerevisiae cells degrade proline into glutamate via the proline utilization pathway, shown here (1, 4). 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 (4). 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 (2, 5). PUT1 and PUT2 are also subject to regulation by an effect known as nitrogen catabolite repression (NCR) (6, 7). NCR prevents utilization of proline as a nitrogen source if better nitrogen compounds such as ammonia, asparagine, or glutamine are present. PUT1 downregulation by NCR is mediated by the transcription factors Ure2p and Dal80p (7, 8). In the presence of proline and the absence of a preferred nitrogen source, NCR is released by the GATA transcriptional activators Gln3p and Gat1p (9, 8). Unrelated to NCR, PUT1 expression is also induced by rapamycin (9) and repressed by Spt10p (10). Spt10p is a global transcription factor that negatively regulates PUT1 by binding to a TATA element in the PUT1 promoter (10). Additionally, Put1p activity requires the presence of oxygen and this form of regulation is abolished when cells are respiratory deficient (11).

PUT1 gene mutations result in the inability of yeast to grow when proline is the sole nitrogen source. The lack of functional Put1p causes an accumulation of proline that has been linked to improved cell viability after freezing and desiccation stress (12). Mutations in PUT1 orthologs lead to impaired motor and phototactic behavior in flies (13), impaired sensorimotor behavior in mice (14), and are associated with human (OMIM) psychiatric and behavioral phenotypes such as the autosomal recessive disease Type 1 hyperprolinemia (OMIM, 15) and schizophrenia (OMIM, 16).

Last updated: 2005-09-06 Contact SGD

References cited on this page View Complete Literature Guide for PUT1
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) 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
3) Wang SS and Brandriss MC  (1986) Proline utilization in Saccharomyces cerevisiae: analysis of the cloned PUT1 gene. Mol Cell Biol 6(7):2638-45
4) 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
5) 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
6) 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
7) 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
8) 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
9) Saxena D, et al.  (2003) Rapamycin treatment results in GATA factor-independent hyperphosphorylation of the proline utilization pathway activator in Saccharomyces cerevisiae. Eukaryot Cell 2(3):552-9
10) 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
11) Wang SS and Brandriss MC  (1987) Proline utilization in Saccharomyces cerevisiae: sequence, regulation, and mitochondrial localization of the PUT1 gene product. Mol Cell Biol 7(12):4431-40
12) Takagi H, et al.  (2000) Proline accumulation by mutation or disruption of the proline oxidase gene improves resistance to freezing and desiccation stresses in Saccharomyces cerevisiae. FEMS Microbiol Lett 184(1):103-8
13) Hayward DC, et al.  (1993) The sluggish-A gene of Drosophila melanogaster is expressed in the nervous system and encodes proline oxidase, a mitochondrial enzyme involved in glutamate biosynthesis. Proc Natl Acad Sci U S A 90(7):2979-83
14) Gogos JA, et al.  (1999) The gene encoding proline dehydrogenase modulates sensorimotor gating in mice. Nat Genet 21(4):434-9
15) Jaeken J, et al.  (1996) Association of hyperprolinaemia type I and heparin cofactor II deficiency with CATCH 22 syndrome: evidence for a contiguous gene syndrome locating the proline oxidase gene. J Inherit Metab Dis 19(3):275-7
16) Liu H, et al.  (2002) Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia. Proc Natl Acad Sci U S A 99(6):3717-22