MET7/YOR241W Summary Help

Standard Name MET7 1, 2
Systematic Name YOR241W
Alias MET23 1 , 3
Feature Type ORF, Verified
Description Folylpolyglutamate synthetase; catalyzes extension of the glutamate chains of the folate coenzymes, required for methionine synthesis and for maintenance of mitochondrial DNA; protein abundance increases in response to DNA replication stress (3, 4, 5 and see Summary Paragraph)
Name Description METhionine requiring 1, 3
Chromosomal Location
ChrXV:786995 to 788641 | ORF Map | GBrowse
Gbrowse
Genetic position: 136 cM
Gene Ontology Annotations All MET7 GO evidence and references
  View Computational GO annotations for MET7
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 34 genes
Resources
Pathways
Classical genetics
null
Large-scale survey
null
overexpression
Resources
123 total interaction(s) for 109 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 3
  • Affinity Capture-RNA: 3
  • Protein-peptide: 1
  • Reconstituted Complex: 1

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Lethality: 1
  • Negative Genetic: 23
  • Phenotypic Enhancement: 23
  • Phenotypic Suppression: 1
  • Positive Genetic: 60
  • Synthetic Growth Defect: 3
  • Synthetic Lethality: 3

Resources
Expression Summary
histogram
Resources
Length (a.a.) 548
Molecular Weight (Da) 62,151
Isoelectric Point (pI) 9.44
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXV:786995 to 788641 | ORF Map | GBrowse
SGD ORF map
Genetic position: 136 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1647 786995..788641 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 SGDIDS000005767
SUMMARY PARAGRAPH for MET7

Met7p is a folypolyglutamate synthetase (FPGS) which works in concert with the dihydrofolate synthetase (DHFS) Fol3p to add glutamyl side chains to de novo synthesized folate coenzymes. In organisms that generate folate cofactors de novo (plants, bacteria, and fungi), the binding of glutamate to folate derivatives is achieved by two reactions catalyzed by DHFS and FPGS, respectively. Fol3p catalyzes the binding of the first glutamyl side chain to dihydropteroate to yield dihydrofolate, then Met7p catalyzes the extension of the glutamate chains of folylmonoglutamates in an ATP-dependent reaction (3).

In the cytosol, folate coenzymes are implicated in purine and thymidylate synthesis as well as in the biogenesis of the methyl group of methionine. In mitochondria, 10-formyltetrahydrofolate is necessary for the formylation of the initiator tRNA and thus for mitochondrial protein synthesis. met7 null mutants were originally identified as methionine auxotrophs (1), indicating that Met7p activity is required for methionine biosynthesis. In addition, Met7p is necessary for the maintenance of mitochondrial DNA, as mitochondrial protein synthesis is required for maintenance of an intact mitochondrial genome in S. cerevisiae, and inhibition of mitochondrial protein synthesis by the use of antifolates induces cytoplasmic respiration-deficient strains (3). Studies by Cherest et al. argue for the existence of only a cytosolic form of Met7p, favoring the hypothesis that mitochondrial integrity depends on the presence of a metabolite whose synthesis takes place in the cytosol and is strictly dependent on polyglutamylation of folate coenzymes (3).

In E. coli, which is able to synthesize folates, DHFS and FPGS activities exist in a bifunctional protein encoded by the FolC gene (3). A bifunctional protein also exists in the human malaria parasite Plasmodium falciparum (6). Mammalian cells, which do not synthesize folates de novo, produce only FPGS and thus depend exclusively on the intake of exogenously supplied folic acid (7, 8). Met7p, which shows significant similarities with Fol3p and Rma1p, is more closely related to the human FPGS than to the E. coli FPGS/DHFS enzyme. Fol3p and Rma1p, however, are more similar to the E. coli enzyme (3).

MET7 has also been implicated, by two genome-wide surveys, in the control of telomere length (9, 10).

Last updated: 2006-06-30 Contact SGD

References cited on this page View Complete Literature Guide for MET7
1) Masselot M and De Robichon-Szulmajster H  (1975) Methionine biosynthesis in Saccharomyces cerevisiae. I. Genetical analysis of auxotrophic mutants. Mol Gen Genet 139(2):121-32
2) Boyer J, et al.  (1996) Sequence and analysis of a 26.9 kb fragment from chromosome XV of the yeast Saccharomyces cerevisiae. Yeast 12(15):1575-86
3) Cherest H, et al.  (2000) Polyglutamylation of folate coenzymes is necessary for methionine biosynthesis and maintenance of intact mitochondrial genome in Saccharomyces cerevisiae. J Biol Chem 275(19):14056-63
4) DeSouza L, et al.  (2000) Disruption of cytoplasmic and mitochondrial folylpolyglutamate synthetase activity in Saccharomyces cerevisiae. Arch Biochem Biophys 376(2):299-312
5) 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
6) Salcedo E, et al.  (2001) A bifunctional dihydrofolate synthetase--folylpolyglutamate synthetase in Plasmodium falciparum identified by functional complementation in yeast and bacteria. Mol Biochem Parasitol 112(2):239-52
7) Wang X, et al.  (2006) Thoc1/Hpr1/p84 is essential for early embryonic development in the mouse. Mol Cell Biol 26(11):4362-7
8) Lo YC, et al.  (2006) Sgs1 regulates gene conversion tract lengths and crossovers independently of its helicase activity. Mol Cell Biol 26(11):4086-94
9) Askree SH, et al.  (2004) A genome-wide screen for Saccharomyces cerevisiae deletion mutants that affect telomere length. Proc Natl Acad Sci U S A 101(23):8658-63
10) Gatbonton T, et al.  (2006) Telomere length as a quantitative trait: genome-wide survey and genetic mapping of telomere length-control genes in yeast. PLoS Genet 2(3):e35