SHM2/YLR058C Summary Help

SHM2 BASIC INFORMATION

Standard Name SHM2
Systematic Name YLR058C
Alias SHMT2
Feature Type ORF, Verified
Description Cytosolic serine hydroxymethyltransferase, converts serine to glycine plus 5,10 methylenetetrahydrofolate; major isoform involved in generating precursors for purine, pyrimidine, amino acid, and lipid biosynthesis (1, 2 and see Summary Paragraph)
Name Description Serine HydroxyMethyltransferase 2
GO Annotations All SHM2 GO evidence and references
    View Computational GO annotations for SHM2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Pathways
Mutant Phenotype All SHM2 Phenotype details and references
Classical genetics
null
overexpression
Large-scale survey
null
Interactions SHM2 All interactions details and references
40 total interaction(s) for 36 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 22
  • Two-hybrid: 3
Genetic Interactions
  • Synthetic Growth Defect: 4
  • Synthetic Lethality: 11
Sequence Information
ChrXII:259402 to 257993 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Last Update Coordinates: 1996-07-31 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates		 Chromosomal
Coordinates		 Most Recent Updates
Coordinates Sequence
CDS 1..1410 259402..257993 1996-07-31 1996-07-31
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | UniProtKB
Primary SGDIDS000004048

SHM2 RESOURCES

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SGD ORF map
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  • Functional Analysis

Click on histogram for expression summary
Expression Summary histogram

ADDITIONAL INFORMATION for SHM2

SUMMARY PARAGRAPH for SHM2

SHM2 encodes the cytosolic isoform of serine hydroxymethyltransferase (SHMT) (2), an enzyme which reversibly converts serine to the products glycine and 5,10 methylene tetrahydrofolate (CH2-THF). CH2-THF serves as a one-carbon donor for reactions leading into purine, pyrimidine, amino acid, and lipid biosynthesis (1). Shm2p is responsible for about 95% of the total cellular SHMT activity, with the mitochondrial isoform Shm1p contributing the remainder; in serine-rich conditions, Shm2p is the major source of one-carbon units and glycine produced from serine (2, 1).

SHM2 transcription is repressed by adenine, and this repression is regulated by the transcription factors Bas1p and Pho2p (3). Transcription of SHM2, along with that of other genes involved in one-carbon metabolism, is also repressed under conditions of glycine limitation (4, 5), and this regulatory effect requires Bas1p but is at least partially independent of Pho2p (4). Transcription is induced in a Bas1p-independent manner during methionine limitation (4).

Although the shm2 null mutation confers no apparent phenotype (2), shm2 exhibits a triple synthetic lethal genetic interaction with srp40 and ade3 null mutations (6). Genetic interaction with ADE3 is expected, since Ade3p is also involved in synthesis of tetrahydrofolate compounds, and in fact in some genetic backgrounds, the shm2 ade3 double mutant is inviable (7). However, in a genetic background in which the shm2 ade3 double mutant is viable, a triple srp40 shm2 ade3 null mutant is inviable, which is surprising since there is no obvious connection between these two cytoplasmic biosynthetic enzymes and Srp40p, a nucleolar protein involved in ribosome assembly. Furthermore, a catalytically inactive mutant version of SHM2 can rescue the lethality, suggesting that Shm2p may have an additional non-catalytic function (6). The observation that overproduction of the catalytically inactive mutant Shm2p causes a dramatic increase in cell size also suggests that Shm2p may have a function in addition to its SHMT enzymatic activity (6).

Shm1p and Shm2p have similarity to other SHMTs, which are conserved from bacteria to humans (2, 8). Mutation of an isoform of SHMT in C. elegans has a maternal effect lethal phenotype (8), and the human ortholog of Shm2p, SHMT1 (OMIM) is implicated in Smith-Magenis syndrome.

Last updated: 2008-01-29

REFERENCES CITED ON THIS PAGE [View Complete Literature Guide for SHM2]

1) Kastanos EK, et al.  (1997) Role of mitochondrial and cytoplasmic serine hydroxymethyltransferase isozymes in de novo purine synthesis in Saccharomyces cerevisiae. Biochemistry 36(48):14956-64
2) McNeil JB, et al.  (1994) Cloning and molecular characterization of three genes, including two genes encoding serine hydroxymethyltransferases, whose inactivation is required to render yeast auxotrophic for glycine. J Biol Chem 269(12):9155-65
3) Denis V and Daignan-Fornier B  (1998) Synthesis of glutamine, glycine and 10-formyl tetrahydrofolate is coregulated with purine biosynthesis in Saccharomyces cerevisiae. Mol Gen Genet 259(3):246-55
4) Subramanian M, et al.  (2005) Transcriptional regulation of the one-carbon metabolism regulon in Saccharomyces cerevisiae by Bas1p. Mol Microbiol 57(1):53-69
5) Gelling CL, et al.  (2004) Identification of a novel one-carbon metabolism regulon in Saccharomyces cerevisiae. J Biol Chem 279(8):7072-81
6) Yang Y and Meier UT  (2003) Genetic interaction between a chaperone of small nucleolar ribonucleoprotein particles and cytosolic serine hydroxymethyltransferase. J Biol Chem 278(26):23553-60
7) Nigavekar SS and Cannon JF  (2002) Characterization of genes that are synthetically lethal with ade3 or leu2 in Saccharomyces cerevisiae. Yeast 19(2):115-22
8) Vatcher GP, et al.  (1998) Serine hydroxymethyltransferase is maternally essential in Caenorhabditis elegans. J Biol Chem 273(11):6066-73