MET12/YPL023C Summary Help

Standard Name MET12 1
Systematic Name YPL023C
Feature Type ORF, Verified
Description Protein with MTHFR activity in vitro; null mutant has no phenotype and is prototrophic for methionine; MET13 encodes major isozyme of methylenetetrahydrofolate reductase (MTHFR) (1 and see Summary Paragraph)
Name Description METhionine requiring 2
Chromosomal Location
ChrXVI:506312 to 504339 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All MET12 GO evidence and references
Molecular Function
Manually curated
Biological Process
Cellular Component
Regulators 1 genes
Classical genetics
Large-scale survey
65 total interaction(s) for 52 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 8
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 1
  • Biochemical Activity: 3
  • Protein-peptide: 3

Genetic Interactions
  • Negative Genetic: 44
  • Positive Genetic: 3
  • Synthetic Growth Defect: 1
  • Synthetic Rescue: 1

Expression Summary
Length (a.a.) 657
Molecular Weight (Da) 73,941
Isoelectric Point (pI) 5.12
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXVI:506312 to 504339 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1974 506312..504339 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000005944

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 (1). Both Met12p and Met13p have been shown to have MTHFR activity in crude extracts, though for technical reasons, only the reverse reaction was assayed (1). 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 (1, 3). In conditions where both MET13 mRNA and Met13p activity are detectable, MET12 mRNA is detectable, but MTHFR activity from Met12p is not (1). In addition, overexpression of MET12 failed to rescue the methionine requirement of the MET13 deletion strain (1). Overexpression of the human MTHFR complements the methionine auxotrophy of met13 cells, but overexpression of the E. coli enzyme does not (1, 3).

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 (1).

Deficiency of MTHFR is the most common genetic defect in folate metabolism in humans, resulting in hyperhomocysteinemia, homocystinuria, and hypomethionemia (1). Homocystinuria is sometimes associated with psychotic symptoms (4). Elevelated levels of homocysteine, due to MTHFR deficiency, are also associated with increased risks of vascular disease and neural tube defects (1).

Last updated: 2008-08-05 Contact SGD

References cited on this page View Complete Literature Guide for MET12
1) Raymond RK, et al.  (1999) Saccharomyces cerevisiae expresses two genes encoding isozymes of methylenetetrahydrofolate reductase. Arch Biochem Biophys 372(2):300-8
2) 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
3) Shan X, et al.  (1999) Functional characterization of human methylenetetrahydrofolate reductase in Saccharomyces cerevisiae. J Biol Chem 274(46):32613-8
4) Foury F  (1997) Human genetic diseases: a cross-talk between man and yeast. Gene 195(1):1-10