MET13/YGL125W Summary Help

Standard Name MET13 1
Systematic Name YGL125W
Alias MET11 , MRPL45 2
Feature Type ORF, Verified
Description Major isozyme of methylenetetrahydrofolate reductase; catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate in the methionine biosynthesis pathway (3 and see Summary Paragraph)
Name Description METhionine requiring 1
Chromosomal Location
ChrVII:272520 to 274322 | ORF Map | GBrowse
Gbrowse
Genetic position: -77 cM
Gene Ontology Annotations All MET13 GO evidence and references
  View Computational GO annotations for MET13
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
High-throughput
Regulators 10 genes
Resources
Pathways
Classical genetics
null
Large-scale survey
null
Resources
30 total interaction(s) for 23 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 7
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 2
  • PCA: 1
  • Protein-RNA: 1

Genetic Interactions
  • Negative Genetic: 12
  • Positive Genetic: 2
  • Synthetic Lethality: 2

Resources
Expression Summary
histogram
Resources
Length (a.a.) 600
Molecular Weight (Da) 68,560
Isoelectric Point (pI) 5.63
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrVII:272520 to 274322 | ORF Map | GBrowse
SGD ORF map
Genetic position: -77 cM
Last Update Coordinates: 2011-02-03 | Sequence: 2003-01-06
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1803 272520..274322 2011-02-03 2003-01-06
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 SGDIDS000003093
SUMMARY PARAGRAPH for MET13

There are two genes in S. cerevisiae with sequence similarity to methylenetetrahydrofolate reductase (MTHFR), MET13 and MET12. MTHFR catalyzes the reduction of N5,N10-methylenetetrahydrofolate to N5-methyltetrahydrofolate. This reaction commits a methyl group from N5,N10-methylenetetrahydrofolate to the synthesis of methionine. In the subsequent reaction, the methyl group is transferred to homocysteine to produce methionine (3). Both Met12p and Met13p have been shown to have MTHFR activity in crude extracts, though for technical reasons, only the reverse reaction was assayed (3). However, by phenotypic analysis, MET13 appears to be the major or sole source of methionine biosynthetic activity in standard laboratory conditions. Disruption of MET13 causes methionine auxotrophy, while disruption of MET12 causes no detectable phenotype (3, 4). In conditions where both MET13 mRNA and Met13p activity are detectable, MET12 mRNA is detectable, but MTHFR activity from Met12p is not (3). In addition, overexpression of MET12 failed to rescue the methionine requirement of the MET13 deletion strain (3). Overexpression of the human MTHFR complements the methionine auxotrophy of met13 cells, but overexpression of the E. coli enzyme does not (3, 4).

Both MET12 and MET13 have sequence similarity to the approximately 300 amino acid catalytic domain of MTHFR from E. coli and from H. sapiens. In addition, both MET12 and MET13 share additional sequence similarity with the human MTHFR gene in the C-terminal region, which contains the binding site for S-adenosyl-methionine, which is known to regulate the human enzyme (3).

Deficiency of MTHFR is the most common genetic defect in folate metabolism in humans, resulting in hyperhomocysteinemia, homocystinuria, and hypomethionemia (3). Homocystinuria is sometimes associated with psychotic symptoms (5). Elevelated levels of homocysteine, due to MTHFR deficiency, are also associated with increased risks of vascular disease and neural tube defects (3).

In early purifications of the mitochondrial ribosome, MET13 was identified as a component of the large mitochondrial ribosomal subunit (2) and was called YmL45 (2) or MRPL45 (6). It has subsequently been shown that this was an error (7).

Last updated: 2008-08-05 Contact SGD

References cited on this page View Complete Literature Guide for MET13
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) Kitakawa M, et al.  (1997) Identification and characterization of the genes for mitochondrial ribosomal proteins of Saccharomyces cerevisiae. Eur J Biochem 245(2):449-56
3) Raymond RK, et al.  (1999) Saccharomyces cerevisiae expresses two genes encoding isozymes of methylenetetrahydrofolate reductase. Arch Biochem Biophys 372(2):300-8
4) Shan X, et al.  (1999) Functional characterization of human methylenetetrahydrofolate reductase in Saccharomyces cerevisiae. J Biol Chem 274(46):32613-8
5) Foury F  (1997) Human genetic diseases: a cross-talk between man and yeast. Gene 195(1):1-10
6) Graack HR and Wittmann-Liebold B  (1998) Mitochondrial ribosomal proteins (MRPs) of yeast. Biochem J 329 ( Pt 3)():433-48
7) Fujita K, et al.  (2001) Cross-genomic analysis of the translational systems of various organisms. J Ind Microbiol Biotechnol 27(3):163-9