SHM1

UniProt ID: P37292
Organism: Saccharomyces cerevisiae S288C
Review Status: DRAFT
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Gene Description

SHM1 encodes the mitochondrial serine hydroxymethyltransferase, a pyridoxal 5'-phosphate-dependent enzyme with an N-terminal mitochondrial transit peptide that reversibly converts L-serine and tetrahydrofolate to glycine and 5,10-methylenetetrahydrofolate. Although it accounts for only about 5% of total cellular SHMT activity, its specific activity in mitochondria is high, and it is a major supplier of one-carbon units for purine, thymidylate and methionine synthesis. Its direction depends on nutrition: on glycine it is the predominant isozyme forming serine from glycine and one-carbon units, and it contributes one-carbon units but little glycine when both amino acids are present. Shm1 acts in parallel with the cytosolic paralog Shm2 and with Gly1 and Agx1 in glycine/serine interconversion; the classical tmp3 mutant is shm1.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004372 glycine hydroxymethyltransferase activity
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PANTHER PTN000188065 (SHMT family; E. coli GlyA, human SHMT1/SHMT2, plant and Plasmodium SHMTs); both yeast paralogs are among the experimental sources.
Reason: Ser/gly hydroxymethyltransferase activity is ancestral to the whole SHMT family and conserved in SHM1; inheritance is sound.
Supporting Evidence:
file:yeast/SHM1/SHM1-uniprot.txt
FUNCTION: Interconversion of serine and glycine.
GO:0004372 glycine hydroxymethyltransferase activity
IEA
GO_REF:0000120
ACCEPT
Summary: IEA from InterPro IPR001085 (serine hydroxymethyltransferase) + RHEA:15481.
Reason: Correct core activity (EC 2.1.2.1).
Supporting Evidence:
file:yeast/SHM1/SHM1-uniprot.txt
FUNCTION: Interconversion of serine and glycine.
GO:0004372 glycine hydroxymethyltransferase activity
IMP
PMID:1100397
Isolation and properties of a thymidylate-less mutant in Sac...
ACCEPT
Summary: IMP from Luzzati 1975: the tmp3 mutant (later shown to be shm1) has a 60% decrease in SHMT specific activity in crude extracts.
Reason: Genetic evidence that SHM1 encodes an SHMT activity; consistent with the later cloning that assigned SHM1 to the mitochondrial isozyme.
Supporting Evidence:
PMID:1100397
Crude extracts of this mutant present a 60% decrease of serine transhydroxymethylase specific activity as compared to a wild-type strain
PMID:8132653
subcellular fractionation studies all suggested that the SHM1 gene encodes the mitochondrial SHMT, while the SHM2 gene encodes the cytosolic enzyme
GO:0004372 glycine hydroxymethyltransferase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from ALL-CHORISMATE-PWY-1 (superpathway of chorismate metabolism), assigning the serine hydroxymethyltransferase reaction to SHM1.
Reason: The molecular function is correct irrespective of which YeastPathways pathway generated the row. Note that superpathway of chorismate metabolism is a superpathway context in which SHMT only supplies 5,10-methylene-THF; the MF itself is still right.
Supporting Evidence:
file:yeast/SHM1/SHM1-uniprot.txt
FUNCTION: Interconversion of serine and glycine.
GO:0004372 glycine hydroxymethyltransferase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from FOLSYN-PWY-1 (superpathway of tetrahydrofolate biosynthesis and salvage), assigning the serine hydroxymethyltransferase reaction to SHM1.
Reason: The molecular function is correct irrespective of which YeastPathways pathway generated the row.
Supporting Evidence:
file:yeast/SHM1/SHM1-uniprot.txt
FUNCTION: Interconversion of serine and glycine.
GO:0004372 glycine hydroxymethyltransferase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from GLYSYN-PWY (glycine biosynthesis I), assigning the serine hydroxymethyltransferase reaction to SHM1.
Reason: The molecular function is correct irrespective of which YeastPathways pathway generated the row.
Supporting Evidence:
file:yeast/SHM1/SHM1-uniprot.txt
FUNCTION: Interconversion of serine and glycine.
GO:0004372 glycine hydroxymethyltransferase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from PWY-2201 (folate transformations I), assigning the serine hydroxymethyltransferase reaction to SHM1.
Reason: The molecular function is correct irrespective of which YeastPathways pathway generated the row.
Supporting Evidence:
file:yeast/SHM1/SHM1-uniprot.txt
FUNCTION: Interconversion of serine and glycine.
GO:0004372 glycine hydroxymethyltransferase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from PWY3O-20 (folate polyglutamylation), assigning the serine hydroxymethyltransferase reaction to SHM1.
Reason: The molecular function is correct irrespective of which YeastPathways pathway generated the row. Note that folate polyglutamylation is a superpathway context in which SHMT only supplies 5,10-methylene-THF; the MF itself is still right.
Supporting Evidence:
file:yeast/SHM1/SHM1-uniprot.txt
FUNCTION: Interconversion of serine and glycine.
GO:0004372 glycine hydroxymethyltransferase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from PWY3O-230 (serine biosynthesis from glyoxylate), assigning the serine hydroxymethyltransferase reaction to SHM1.
Reason: The molecular function is correct irrespective of which YeastPathways pathway generated the row.
Supporting Evidence:
file:yeast/SHM1/SHM1-uniprot.txt
FUNCTION: Interconversion of serine and glycine.
GO:0004372 glycine hydroxymethyltransferase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from PWY3O-261 (superpathway of serine and glycine biosynthesis), assigning the serine hydroxymethyltransferase reaction to SHM1.
Reason: The molecular function is correct irrespective of which YeastPathways pathway generated the row.
Supporting Evidence:
file:yeast/SHM1/SHM1-uniprot.txt
FUNCTION: Interconversion of serine and glycine.
GO:0004372 glycine hydroxymethyltransferase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from PWY3O-697 (folate interconversions), assigning the serine hydroxymethyltransferase reaction to SHM1.
Reason: The molecular function is correct irrespective of which YeastPathways pathway generated the row.
Supporting Evidence:
file:yeast/SHM1/SHM1-uniprot.txt
FUNCTION: Interconversion of serine and glycine.
GO:0005739 mitochondrion
HDA
PMID:14576278
The proteome of Saccharomyces cerevisiae mitochondria.
ACCEPT
Summary: HDA from a mitochondrial proteome (PMID:14576278) detecting Shm1 in purified mitochondria.
Reason: Consistent with the N-terminal transit peptide and fractionation data; Shm1 is the mitochondrial isozyme.
Supporting Evidence:
PMID:14576278
The proteins of highly pure yeast mitochondria were separated by several independent methods and analyzed by tandem MS
PMID:8132653
subcellular fractionation studies all suggested that the SHM1 gene encodes the mitochondrial SHMT, while the SHM2 gene encodes the cytosolic enzyme
GO:0005739 mitochondrion
HDA
PMID:16823961
Toward the complete yeast mitochondrial proteome: multidimen...
ACCEPT
Summary: HDA from a mitochondrial proteome (PMID:16823961) detecting Shm1 in purified mitochondria.
Reason: Consistent with the N-terminal transit peptide and fractionation data; Shm1 is the mitochondrial isozyme.
Supporting Evidence:
PMID:16823961
A total of 851 different proteins (PROMITO dataset) were identified
PMID:8132653
subcellular fractionation studies all suggested that the SHM1 gene encodes the mitochondrial SHMT, while the SHM2 gene encodes the cytosolic enzyme
GO:0005739 mitochondrion
HDA
PMID:24769239
Quantitative variations of the mitochondrial proteome and ph...
ACCEPT
Summary: HDA from a mitochondrial proteome (PMID:24769239) detecting Shm1 in purified mitochondria.
Reason: Consistent with the N-terminal transit peptide and fractionation data; Shm1 is the mitochondrial isozyme.
Supporting Evidence:
PMID:24769239
we performed an overall quantitative proteomic and phosphoproteomic study of isolated mitochondria extracted from yeast
PMID:8132653
subcellular fractionation studies all suggested that the SHM1 gene encodes the mitochondrial SHMT, while the SHM2 gene encodes the cytosolic enzyme
GO:0005739 mitochondrion
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN000188068 (mitochondrial SHMT2-like node; human SHMT2, mouse Shmt2, Arabidopsis SHM, SHM1 itself).
Reason: Correct; Shm1 belongs to the mitochondrial SHMT lineage and has a cleavable transit peptide.
Supporting Evidence:
PMID:8132653
subcellular fractionation studies all suggested that the SHM1 gene encodes the mitochondrial SHMT, while the SHM2 gene encodes the cytosolic enzyme
GO:0005739 mitochondrion
IEA
GO_REF:0000044
ACCEPT
Summary: IEA from UniProt subcellular location keyword mapping (SL-0173 mitochondrion).
Reason: Correct.
Supporting Evidence:
file:yeast/SHM1/SHM1-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion.
GO:0005739 mitochondrion
IMP
PMID:6271
Two forms of serine transhydroxymethylase, one absent in a t...
ACCEPT
Summary: IMP from Zelikson & Luzzati 1976: of two SHMT forms, one is absent in the tmp3 (shm1) mutant; the missing form is the mitochondrial enzyme.
Reason: Deferred to curator (abstract-only, no abstract text); consistent with the later molecular assignment of SHM1 to mitochondria.
Supporting Evidence:
PMID:6271
Two forms of serine transhydroxymethylase, one absent in a thymidylate-less mutant in Saccharomyces cerevisiae
PMID:8132653
subcellular fractionation studies all suggested that the SHM1 gene encodes the mitochondrial SHMT, while the SHM2 gene encodes the cytosolic enzyme
GO:0005739 mitochondrion
IMP
PMID:9398220
Role of mitochondrial and cytoplasmic serine hydroxymethyltr...
ACCEPT
Summary: IMP from Kastanos et al. 1997: subcellular fractionation of shm mutants shows mitochondrial SHMT activity (5% of total, high specific activity) depends on SHM1.
Reason: Experimental localization of the Shm1 activity.
Supporting Evidence:
PMID:9398220
Cell subfractionation experiments indicated that while only 5% of total activity was localized in the mitochondria, the specific activity in that compartment was much higher than in the cytoplasm
PMID:9398220
In Saccharomyces cerevisiae, mitochondrial and cytoplasmic SHMT isozymes are encoded by distinct nuclear genes (SHM1 and SHM2)
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: YeastPathways RCA placing the ALL-CHORISMATE-PWY-1 (superpathway of chorismate metabolism) SHMT reaction in the cytosol, attributed to both paralogs.
Reason: Shm1 is the mitochondrial isozyme (transit peptide, fractionation, mitochondrial proteomes); the cytosolic SHMT reaction is catalysed by Shm2. The RCA conversion assigned the pathway compartment to every enzyme of the reaction.
Supporting Evidence:
PMID:8132653
subcellular fractionation studies all suggested that the SHM1 gene encodes the mitochondrial SHMT, while the SHM2 gene encodes the cytosolic enzyme
PMID:9398220
In Saccharomyces cerevisiae, mitochondrial and cytoplasmic SHMT isozymes are encoded by distinct nuclear genes (SHM1 and SHM2)
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: YeastPathways RCA placing the FOLSYN-PWY-1 (superpathway of tetrahydrofolate biosynthesis and salvage) SHMT reaction in the cytosol, attributed to both paralogs.
Reason: Shm1 is the mitochondrial isozyme (transit peptide, fractionation, mitochondrial proteomes); the cytosolic SHMT reaction is catalysed by Shm2. The RCA conversion assigned the pathway compartment to every enzyme of the reaction.
Supporting Evidence:
PMID:8132653
subcellular fractionation studies all suggested that the SHM1 gene encodes the mitochondrial SHMT, while the SHM2 gene encodes the cytosolic enzyme
PMID:9398220
In Saccharomyces cerevisiae, mitochondrial and cytoplasmic SHMT isozymes are encoded by distinct nuclear genes (SHM1 and SHM2)
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: YeastPathways RCA placing the GLYSYN-PWY (glycine biosynthesis I) SHMT reaction in the cytosol, attributed to both paralogs.
Reason: Shm1 is the mitochondrial isozyme (transit peptide, fractionation, mitochondrial proteomes); the cytosolic SHMT reaction is catalysed by Shm2. The RCA conversion assigned the pathway compartment to every enzyme of the reaction.
Supporting Evidence:
PMID:8132653
subcellular fractionation studies all suggested that the SHM1 gene encodes the mitochondrial SHMT, while the SHM2 gene encodes the cytosolic enzyme
PMID:9398220
In Saccharomyces cerevisiae, mitochondrial and cytoplasmic SHMT isozymes are encoded by distinct nuclear genes (SHM1 and SHM2)
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: YeastPathways RCA placing the PWY-2201 (folate transformations I) SHMT reaction in the cytosol, attributed to both paralogs.
Reason: Shm1 is the mitochondrial isozyme (transit peptide, fractionation, mitochondrial proteomes); the cytosolic SHMT reaction is catalysed by Shm2. The RCA conversion assigned the pathway compartment to every enzyme of the reaction.
Supporting Evidence:
PMID:8132653
subcellular fractionation studies all suggested that the SHM1 gene encodes the mitochondrial SHMT, while the SHM2 gene encodes the cytosolic enzyme
PMID:9398220
In Saccharomyces cerevisiae, mitochondrial and cytoplasmic SHMT isozymes are encoded by distinct nuclear genes (SHM1 and SHM2)
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: YeastPathways RCA placing the PWY3O-20 (folate polyglutamylation) SHMT reaction in the cytosol, attributed to both paralogs.
Reason: Shm1 is the mitochondrial isozyme (transit peptide, fractionation, mitochondrial proteomes); the cytosolic SHMT reaction is catalysed by Shm2. The RCA conversion assigned the pathway compartment to every enzyme of the reaction.
Supporting Evidence:
PMID:8132653
subcellular fractionation studies all suggested that the SHM1 gene encodes the mitochondrial SHMT, while the SHM2 gene encodes the cytosolic enzyme
PMID:9398220
In Saccharomyces cerevisiae, mitochondrial and cytoplasmic SHMT isozymes are encoded by distinct nuclear genes (SHM1 and SHM2)
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: YeastPathways RCA placing the PWY3O-230 (serine biosynthesis from glyoxylate) SHMT reaction in the cytosol, attributed to both paralogs.
Reason: Shm1 is the mitochondrial isozyme (transit peptide, fractionation, mitochondrial proteomes); the cytosolic SHMT reaction is catalysed by Shm2. The RCA conversion assigned the pathway compartment to every enzyme of the reaction.
Supporting Evidence:
PMID:8132653
subcellular fractionation studies all suggested that the SHM1 gene encodes the mitochondrial SHMT, while the SHM2 gene encodes the cytosolic enzyme
PMID:9398220
In Saccharomyces cerevisiae, mitochondrial and cytoplasmic SHMT isozymes are encoded by distinct nuclear genes (SHM1 and SHM2)
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: YeastPathways RCA placing the PWY3O-261 (superpathway of serine and glycine biosynthesis) SHMT reaction in the cytosol, attributed to both paralogs.
Reason: Shm1 is the mitochondrial isozyme (transit peptide, fractionation, mitochondrial proteomes); the cytosolic SHMT reaction is catalysed by Shm2. The RCA conversion assigned the pathway compartment to every enzyme of the reaction.
Supporting Evidence:
PMID:8132653
subcellular fractionation studies all suggested that the SHM1 gene encodes the mitochondrial SHMT, while the SHM2 gene encodes the cytosolic enzyme
PMID:9398220
In Saccharomyces cerevisiae, mitochondrial and cytoplasmic SHMT isozymes are encoded by distinct nuclear genes (SHM1 and SHM2)
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: YeastPathways RCA placing the PWY3O-697 (folate interconversions) SHMT reaction in the cytosol, attributed to both paralogs.
Reason: Shm1 is the mitochondrial isozyme (transit peptide, fractionation, mitochondrial proteomes); the cytosolic SHMT reaction is catalysed by Shm2. The RCA conversion assigned the pathway compartment to every enzyme of the reaction.
Supporting Evidence:
PMID:8132653
subcellular fractionation studies all suggested that the SHM1 gene encodes the mitochondrial SHMT, while the SHM2 gene encodes the cytosolic enzyme
PMID:9398220
In Saccharomyces cerevisiae, mitochondrial and cytoplasmic SHMT isozymes are encoded by distinct nuclear genes (SHM1 and SHM2)
GO:0006545 glycine biosynthetic process
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: IBA glycine biosynthetic process for Shm1 (PTN000188065 IBA).
Reason: Shm1 can form glycine (it contributes to prototrophy in gly1 shm2 backgrounds), but 13C-NMR shows the mitochondrial isozyme supplies one-carbon units rather than glycine when both amino acids are present, and Gly1/Shm2 are the main glycine sources. Non-core for Shm1.
Supporting Evidence:
PMID:9398220
when both serine and glycine were present, the mitochondrial SHMT made a significant contribution of one-carbon units, but not glycine, for purine synthesis
PMID:8132653
Gene disruption studies demonstrated that inactivation of SHM1, SHM2, and GLY1 is required to yield yeast that are completely auxotrophic for glycine
GO:0006545 glycine biosynthetic process
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: IEA glycine biosynthetic process for Shm1 (InterPro IPR001085 mapping).
Reason: Shm1 can form glycine (it contributes to prototrophy in gly1 shm2 backgrounds), but 13C-NMR shows the mitochondrial isozyme supplies one-carbon units rather than glycine when both amino acids are present, and Gly1/Shm2 are the main glycine sources. Non-core for Shm1.
Supporting Evidence:
PMID:9398220
when both serine and glycine were present, the mitochondrial SHMT made a significant contribution of one-carbon units, but not glycine, for purine synthesis
PMID:8132653
Gene disruption studies demonstrated that inactivation of SHM1, SHM2, and GLY1 is required to yield yeast that are completely auxotrophic for glycine
GO:0006545 glycine biosynthetic process
RCA
GO_REF:0000123
KEEP AS NON CORE
Summary: RCA glycine biosynthetic process for Shm1 (YeastPathways GLYSYN-PWY RCA).
Reason: Shm1 can form glycine (it contributes to prototrophy in gly1 shm2 backgrounds), but 13C-NMR shows the mitochondrial isozyme supplies one-carbon units rather than glycine when both amino acids are present, and Gly1/Shm2 are the main glycine sources. Non-core for Shm1.
Supporting Evidence:
PMID:9398220
when both serine and glycine were present, the mitochondrial SHMT made a significant contribution of one-carbon units, but not glycine, for purine synthesis
PMID:8132653
Gene disruption studies demonstrated that inactivation of SHM1, SHM2, and GLY1 is required to yield yeast that are completely auxotrophic for glycine
GO:0006564 L-serine biosynthetic process
RCA
GO_REF:0000123
KEEP AS NON CORE
Summary: YeastPathways RCA from PWY3O-230 (serine biosynthesis from glyoxylate), in which glycine from the glyoxylate route is converted to serine by SHMT.
Reason: Supported: on glycine the mitochondrial SHMT is the predominant isozyme making serine from glycine. This is a conditional (gluconeogenic) route, so it is kept as non-core.
Supporting Evidence:
PMID:9398220
When grown on glycine, the mitochondrial SHMT was the predominant isozyme catalyzing the synthesis of serine from glycine and one-carbon units
GO:0006730 one-carbon metabolic process
IGI
PMID:9398220
Role of mitochondrial and cytoplasmic serine hydroxymethyltr...
ACCEPT
Summary: IGI with SHM2 from Kastanos et al. 1997: shm1/shm2 single and double mutants define the isozyme contributions to one-carbon units for purine synthesis.
Reason: Shm1 provides one-carbon units (5,10-CH2-THF) in mitochondria; this is core.
Supporting Evidence:
PMID:9398220
when both serine and glycine were present, the mitochondrial SHMT made a significant contribution of one-carbon units, but not glycine, for purine synthesis
GO:0006730 one-carbon metabolic process
IMP
PMID:1100397
Isolation and properties of a thymidylate-less mutant in Sac...
ACCEPT
Summary: IMP from Luzzati 1975: tmp3 (shm1) mutant requires thymidylate, methionine, adenine and histidine.
Reason: These are all one-carbon-dependent end products; consistent with Shm1 supplying one-carbon units.
Supporting Evidence:
PMID:1100397
a single mendelian gene controls the multiple requirements for thymidylate, methionine, adenine and histidine
GO:0009070 serine family amino acid biosynthetic process
RCA
GO_REF:0000123
TOO GENERAL
Summary: YeastPathways RCA from superpathway PWY3O-261.
Reason: Correct in a general sense (serine/glycine interconversion) but less informative than the specific processes.
Supporting Evidence:
PMID:9398220
In Saccharomyces cerevisiae, mitochondrial and cytoplasmic SHMT isozymes are encoded by distinct nuclear genes (SHM1 and SHM2)
GO:0030170 pyridoxal phosphate binding
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: IBA pyridoxal phosphate binding (PTN000188065).
Reason: Correct cofactor binding; integral to the SHMT activity rather than a separate function.
Supporting Evidence:
file:yeast/SHM1/SHM1-uniprot.txt
Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
GO:0030170 pyridoxal phosphate binding
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: IEA pyridoxal phosphate binding (InterPro IPR001085/IPR019798 PLP attachment site).
Reason: Correct cofactor binding; integral to the SHMT activity rather than a separate function.
Supporting Evidence:
file:yeast/SHM1/SHM1-uniprot.txt
Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
GO:0035999 folate cycle
IEA
GO_REF:0000120
ACCEPT
Summary: IEA from InterPro IPR001085 + UniPathway UPA00193 (tetrahydrofolate interconversion).
Reason: Correct core process: SHMT converts THF to 5,10-methylene-THF.
Supporting Evidence:
PMID:9398220
when both serine and glycine were present, the mitochondrial SHMT made a significant contribution of one-carbon units, but not glycine, for purine synthesis
GO:0035999 folate cycle
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from FOLSYN-PWY-1 (superpathway of tetrahydrofolate biosynthesis and salvage).
Reason: Correct; SHMT is a central THF-interconverting enzyme.
Supporting Evidence:
PMID:9398220
when both serine and glycine were present, the mitochondrial SHMT made a significant contribution of one-carbon units, but not glycine, for purine synthesis
GO:0035999 folate cycle
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from PWY-2201 (folate transformations I).
Reason: Correct; SHMT is a central THF-interconverting enzyme.
Supporting Evidence:
PMID:9398220
when both serine and glycine were present, the mitochondrial SHMT made a significant contribution of one-carbon units, but not glycine, for purine synthesis
GO:0046417 chorismate metabolic process
RCA
GO_REF:0000123
REMOVE
Summary: YeastPathways RCA from ALL-CHORISMATE-PWY-1 (superpathway of chorismate metabolism), inherited because the superpathway includes folate synthesis downstream of chorismate.
Reason: SHMT does not act on chorismate or any chorismate-derived intermediate; this is a superpathway inheritance artifact.
Supporting Evidence:
file:yeast/SHM1/SHM1-uniprot.txt
FUNCTION: Interconversion of serine and glycine.
GO:0046653 tetrahydrofolate metabolic process
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN000188065 for tetrahydrofolate metabolic process.
Reason: Correct (parent of tetrahydrofolate interconversion).
Supporting Evidence:
PMID:9398220
In Saccharomyces cerevisiae, mitochondrial and cytoplasmic SHMT isozymes are encoded by distinct nuclear genes (SHM1 and SHM2)
GO:0046655 folic acid metabolic process
RCA
GO_REF:0000123
MODIFY
Summary: YeastPathways RCA from PWY3O-20 (folate polyglutamylation), mapped to folic acid metabolic process.
Reason: SHMT neither polyglutamylates folates nor acts on folic acid; within this superpathway its contribution is THF -> 5,10-methylene-THF. The accurate term is tetrahydrofolate interconversion, which the gene already carries.
Proposed replacements: tetrahydrofolate interconversion
Supporting Evidence:
PMID:9398220
In Saccharomyces cerevisiae, mitochondrial and cytoplasmic SHMT isozymes are encoded by distinct nuclear genes (SHM1 and SHM2)
GO:0046655 folic acid metabolic process
RCA
GO_REF:0000123
MODIFY
Summary: YeastPathways RCA from PWY3O-697 (folate interconversions), mapped to folic acid metabolic process.
Reason: The pathway is right but the term is not: SHMT acts on tetrahydrofolate, not on folic acid (pteroylglutamate). The appropriate term is tetrahydrofolate interconversion, which the gene already carries.
Proposed replacements: tetrahydrofolate interconversion
Supporting Evidence:
PMID:9398220
In Saccharomyces cerevisiae, mitochondrial and cytoplasmic SHMT isozymes are encoded by distinct nuclear genes (SHM1 and SHM2)

Core Functions

Mitochondrial PLP-dependent serine/glycine interconversion coupled to THF <-> 5,10-methylene-THF (EC 2.1.2.1); supplies mitochondrial one-carbon units and synthesizes serine from glycine when glycine is the carbon/one-carbon source.

Supporting Evidence:
  • PMID:9398220
    Cell subfractionation experiments indicated that while only 5% of total activity was localized in the mitochondria, the specific activity in that compartment was much higher than in the cytoplasm
  • PMID:9398220
    When grown on glycine, the mitochondrial SHMT was the predominant isozyme catalyzing the synthesis of serine from glycine and one-carbon units
  • PMID:8132653
    subcellular fractionation studies all suggested that the SHM1 gene encodes the mitochondrial SHMT, while the SHM2 gene encodes the cytosolic enzyme

References

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Suggested Questions for Experts

Q: Is Shm1 in the matrix exclusively, or is a cytosolic pool produced from alternative translation initiation (UniProt notes erroneous initiation in two submissions)?

Suggested Experiments

Experiment: 13C-serine/glycine tracing in shm1 versus shm2 strains on glycine as nitrogen source to quantify mitochondrial serine synthesis.

Deep Research

SGD

(SHM1-deep-research-sgd.md)
SGD gene description for SHM1 (yeast) SGD

SGD gene description for SHM1 (yeast)

Mitochondrial serine hydroxymethyltransferase; converts serine to glycine plus 5,10 methylenetetrahydrofolate; involved in generating precursors for purine, pyrimidine, amino acid, and lipid biosynthesis; reverse reaction generates serine

πŸ“š Additional Documentation

Notes

(SHM1-notes.md)

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