MIS1

UniProt ID: P09440
Organism: Saccharomyces cerevisiae S288C
Review Status: DRAFT
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Gene Description

Mitochondrial C1-tetrahydrofolate synthase of Saccharomyces cerevisiae, a homodimeric trifunctional enzyme (subunit about 100 kDa) and the mitochondrial isozyme of cytosolic Ade3. Its N-terminal dehydrogenase/cyclohydrolase domain carries NADP+-dependent 5,10-methylene-THF dehydrogenase (EC 1.5.1.5) and 5,10-methenyl-THF cyclohydrolase (EC 3.5.4.9) activities; its C-terminal domain is an ATP-dependent 10-formyl-THF synthetase (EC 6.3.4.3). Together they interconvert formate, 10-formyl-THF, 5,10-methenyl-THF and 5,10-methylene-THF in the mitochondrial matrix. This links mitochondrial one-carbon units, e.g. from glycine cleavage, with the cytosolic folate pool through formate.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0003824 catalytic activity
IEA
GO_REF:0000002
MARK AS OVER ANNOTATED
Summary: InterPro2GO generic catalytic activity (IPR020867); uninformative given the three specific activities.
Reason: Uninformative root-level MF.
GO:0004329 formate-tetrahydrofolate ligase activity
IDA
PMID:3528153
Purification and characterization of a mitochondrial isozyme...
ACCEPT
Summary: Shannon & Rabinowitz purified the mitochondrial isozyme from an ade3 deletion strain and showed 10-formyl-THF synthetase activity co-purifying with the other two activities.
Supporting Evidence:
PMID:3528153
Synthetase, cyclohydrolase, and dehydrogenase activities in an ade3 deletion strain co-purify 4,000-fold to yield a single protein species
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0004329 formate-tetrahydrofolate ligase activity
IEA
GO_REF:0000120
ACCEPT
Summary: Combined IEA (InterPro FTHFS IPR000559, RHEA:20221, EC 6.3.4.3); correct for the C-terminal synthetase domain.
Supporting Evidence:
file:yeast/MIS1/MIS1-uniprot.txt
(6S)-5,6,7,8-tetrahydrofolate + formate + ATP = (6R)-10-
GO:0004329 formate-tetrahydrofolate ligase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from ALL-CHORISMATE-PWY-1 (superpathway of chorismate metabolism) assigning Mis1 to the formate-tetrahydrofolate ligase reaction. The activity is experimentally shown for the mitochondrial isozyme; correct whatever the pathway context.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0004329 formate-tetrahydrofolate ligase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from FOLSYN-PWY-1 (folate transformations) assigning Mis1 to the formate-tetrahydrofolate ligase reaction. The activity is experimentally shown for the mitochondrial isozyme; correct whatever the pathway context.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0004329 formate-tetrahydrofolate ligase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from PWY-2201 (folate transformations I) assigning Mis1 to the formate-tetrahydrofolate ligase reaction. The activity is experimentally shown for the mitochondrial isozyme; correct whatever the pathway context.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0004329 formate-tetrahydrofolate ligase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from PWY3O-20 (folate polyglutamylation) assigning Mis1 to the formate-tetrahydrofolate ligase reaction. The activity is experimentally shown for the mitochondrial isozyme; correct whatever the pathway context.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0004329 formate-tetrahydrofolate ligase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from PWY3O-697 (folate interconversions) assigning Mis1 to the formate-tetrahydrofolate ligase reaction. The activity is experimentally shown for the mitochondrial isozyme; correct whatever the pathway context.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0004477 methenyltetrahydrofolate cyclohydrolase activity
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT IBA (PTN000002250) for methenyl-THF cyclohydrolase in the DHFR/CH family; Mis1 has direct evidence.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0004477 methenyltetrahydrofolate cyclohydrolase activity
IDA
PMID:3528153
Purification and characterization of a mitochondrial isozyme...
ACCEPT
Summary: Cyclohydrolase activity co-purifies with the mitochondrial isozyme.
Supporting Evidence:
PMID:3528153
Synthetase, cyclohydrolase, and dehydrogenase activities in an ade3 deletion strain co-purify 4,000-fold to yield a single protein species
GO:0004477 methenyltetrahydrofolate cyclohydrolase activity
IEA
GO_REF:0000120
ACCEPT
Summary: Combined IEA (ARBA, RHEA:23700, EC 3.5.4.9); correct.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0004477 methenyltetrahydrofolate cyclohydrolase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from ALL-CHORISMATE-PWY-1 (superpathway of chorismate metabolism) assigning Mis1 to the methenyltetrahydrofolate cyclohydrolase reaction. The activity is experimentally shown for the mitochondrial isozyme; correct whatever the pathway context.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0004477 methenyltetrahydrofolate cyclohydrolase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from FOLSYN-PWY-1 (folate transformations) assigning Mis1 to the methenyltetrahydrofolate cyclohydrolase reaction. The activity is experimentally shown for the mitochondrial isozyme; correct whatever the pathway context.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0004477 methenyltetrahydrofolate cyclohydrolase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from PWY-2201 (folate transformations I) assigning Mis1 to the methenyltetrahydrofolate cyclohydrolase reaction. The activity is experimentally shown for the mitochondrial isozyme; correct whatever the pathway context.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0004477 methenyltetrahydrofolate cyclohydrolase activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from PWY3O-697 (folate interconversions) assigning Mis1 to the methenyltetrahydrofolate cyclohydrolase reaction. The activity is experimentally shown for the mitochondrial isozyme; correct whatever the pathway context.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0004488 methylenetetrahydrofolate dehydrogenase (NADP+) activity
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT IBA for NADP+-dependent methylene-THF dehydrogenase; Mis1 has direct evidence.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0004488 methylenetetrahydrofolate dehydrogenase (NADP+) activity
IDA
PMID:3528153
Purification and characterization of a mitochondrial isozyme...
ACCEPT
Summary: Dehydrogenase activity co-purifies with the mitochondrial isozyme.
Supporting Evidence:
PMID:3528153
Synthetase, cyclohydrolase, and dehydrogenase activities in an ade3 deletion strain co-purify 4,000-fold to yield a single protein species
GO:0004488 methylenetetrahydrofolate dehydrogenase (NADP+) activity
IEA
GO_REF:0000120
ACCEPT
Summary: Combined IEA (ARBA, InterPro THF DH/CH domains, RHEA:22812, EC 1.5.1.5); correct.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0004488 methylenetetrahydrofolate dehydrogenase (NADP+) activity
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA from PWY3O-697 (folate interconversions) assigning Mis1 to the NADP+-dependent methylenetetrahydrofolate dehydrogenase reaction. The activity is experimentally shown for the mitochondrial isozyme; correct whatever the pathway context.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0005524 ATP binding
IEA
GO_REF:0000002
ACCEPT
Summary: InterPro2GO ATP binding (FTHFS domain); the synthetase reaction consumes ATP.
Supporting Evidence:
file:yeast/MIS1/MIS1-uniprot.txt
(6S)-5,6,7,8-tetrahydrofolate + formate + ATP = (6R)-10-
GO:0005737 cytoplasm
RCA
GO_REF:0000123
REMOVE
Summary: YeastPathways RCA (PWY3O-697) placing Mis1 activity in the cytoplasm. Mis1 is the mitochondrial C1-THF synthase; cell fractionation shows the isozyme, unlike cytosolic Ade3, in mitochondria, and proteomics and GFP agree. The cytoplasmic folate-interconversion reactions are carried out by Ade3 (and Mtd1).
Reason: Compartment taken from the pathway, which mixes the cytosolic Ade3 and mitochondrial Mis1 isozymes.
Supporting Evidence:
PMID:3528153
Cell fractionation experiments show that the isozyme, but not C1-tetrahydrofolate synthase, is localized in the mitochondria
GO:0005739 mitochondrion
HDA
PMID:14576278
The proteome of Saccharomyces cerevisiae mitochondria.
ACCEPT
Summary: Mis1 found in the purified mitochondrial proteome.
Supporting Evidence:
PMID:14576278
The proteins of highly pure yeast mitochondria were separated by several independent methods and analyzed by tandem MS
GO:0005739 mitochondrion
HDA
PMID:16823961
Toward the complete yeast mitochondrial proteome: multidimen...
ACCEPT
Summary: Mis1 found in the PROMITO mitochondrial proteome.
Supporting Evidence:
PMID:16823961
A total of 851 different proteins (PROMITO dataset) were
GO:0005739 mitochondrion
HDA
PMID:24769239
Quantitative variations of the mitochondrial proteome and ph...
ACCEPT
Summary: Mis1 quantified in the mitochondrial proteome.
Supporting Evidence:
PMID:24769239
The yeast Saccharomyces cerevisiae is a facultative aerobe able to adapt its metabolism according to the carbon substrate
GO:0005739 mitochondrion
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT IBA at the mitochondrial isozyme node (PTN000002392), with Mis1 as the experimental leaf.
Supporting Evidence:
PMID:3528153
Cell fractionation experiments show that the isozyme, but not C1-tetrahydrofolate synthase, is localized in the mitochondria
GO:0005739 mitochondrion
IDA
PMID:3528153
Purification and characterization of a mitochondrial isozyme...
ACCEPT
Summary: Cell fractionation localises the isozyme to mitochondria.
Supporting Evidence:
PMID:3528153
Cell fractionation experiments show that the isozyme, but not C1-tetrahydrofolate synthase, is localized in the mitochondria
GO:0005739 mitochondrion
IEA
GO_REF:0000044
ACCEPT
Summary: UniProt SubCell mapping (mitochondrion); correct.
Supporting Evidence:
PMID:3528153
Cell fractionation experiments show that the isozyme, but not C1-tetrahydrofolate synthase, is localized in the mitochondria
file:yeast/MIS1/MIS1-uniprot.txt
Mitochondrial isozyme of C-1-tetrahydrofolate synthase. The
GO:0005829 cytosol
IBA
GO_REF:0000033
REMOVE
Summary: PAINT IBA for cytosol at the broad C1-THF synthase node (PTN000002250), which includes cytosolic Ade3 and Mtd1. Mis1 is the mitochondrial C1-THF synthase; cell fractionation shows the isozyme, unlike cytosolic Ade3, in mitochondria, and proteomics and GFP agree. Mis1 has diverged into a mitochondrial paralog, so the cytosolic location does not propagate to it.
Reason: Target-specific evidence that Mis1 is mitochondrial; the IBA node conflates cytosolic and mitochondrial paralogs.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: COMPARTMENT OR COMPLEX MISMATCH WRONG ORTHOLOG OR PARALOG
Sources checked:
PANTHER:PTN000002250 Β· PTN000002250 SUPPORTS SOURCE BUT NOT TARGET
Cytosol is correct for Ade3/Mtd1/MTHFD1 leaves; Mis1 is the experimentally mitochondrial isozyme and separately receives mitochondrion from PTN000002392.
Supporting Evidence:
PMID:3528153
Cell fractionation experiments show that the isozyme, but not C1-tetrahydrofolate synthase, is localized in the mitochondria
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: YeastPathways RCA from ALL-CHORISMATE-PWY-1 (superpathway of chorismate metabolism) placing Mis1 activity in the cytosol (default compartment). Mis1 is the mitochondrial C1-THF synthase; cell fractionation shows the isozyme, unlike cytosolic Ade3, in mitochondria, and proteomics and GFP agree.
Reason: Default-compartment artefact; Mis1 is mitochondrial.
Supporting Evidence:
PMID:3528153
Cell fractionation experiments show that the isozyme, but not C1-tetrahydrofolate synthase, is localized in the mitochondria
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: YeastPathways RCA from FOLSYN-PWY-1 (folate transformations) placing Mis1 activity in the cytosol (default compartment). Mis1 is the mitochondrial C1-THF synthase; cell fractionation shows the isozyme, unlike cytosolic Ade3, in mitochondria, and proteomics and GFP agree.
Reason: Default-compartment artefact; Mis1 is mitochondrial.
Supporting Evidence:
PMID:3528153
Cell fractionation experiments show that the isozyme, but not C1-tetrahydrofolate synthase, is localized in the mitochondria
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: YeastPathways RCA from PWY-2201 (folate transformations I) placing Mis1 activity in the cytosol (default compartment). Mis1 is the mitochondrial C1-THF synthase; cell fractionation shows the isozyme, unlike cytosolic Ade3, in mitochondria, and proteomics and GFP agree.
Reason: Default-compartment artefact; Mis1 is mitochondrial.
Supporting Evidence:
PMID:3528153
Cell fractionation experiments show that the isozyme, but not C1-tetrahydrofolate synthase, is localized in the mitochondria
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: YeastPathways RCA from PWY3O-20 (folate polyglutamylation) placing Mis1 activity in the cytosol (default compartment). Mis1 is the mitochondrial C1-THF synthase; cell fractionation shows the isozyme, unlike cytosolic Ade3, in mitochondria, and proteomics and GFP agree.
Reason: Default-compartment artefact; Mis1 is mitochondrial.
Supporting Evidence:
PMID:3528153
Cell fractionation experiments show that the isozyme, but not C1-tetrahydrofolate synthase, is localized in the mitochondria
GO:0005829 cytosol
RCA
GO_REF:0000123
REMOVE
Summary: YeastPathways RCA from PWY3O-697 (folate interconversions) placing Mis1 activity in the cytosol (default compartment). Mis1 is the mitochondrial C1-THF synthase; cell fractionation shows the isozyme, unlike cytosolic Ade3, in mitochondria, and proteomics and GFP agree.
Reason: Default-compartment artefact; Mis1 is mitochondrial.
Supporting Evidence:
PMID:3528153
Cell fractionation experiments show that the isozyme, but not C1-tetrahydrofolate synthase, is localized in the mitochondria
GO:0016874 ligase activity
IEA
GO_REF:0000117
MARK AS OVER ANNOTATED
Summary: ARBA ligase activity; uninformative parent of formate-tetrahydrofolate ligase activity.
Reason: Uninformative parent of GO:0004329.
GO:0035999 folate cycle
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT IBA for tetrahydrofolate interconversion; all three Mis1 activities are THF one-carbon interconversions.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0035999 folate cycle
IEA
GO_REF:0000041
ACCEPT
Summary: UniPathway mapping (UPA00193); correct.
Supporting Evidence:
file:yeast/MIS1/MIS1-uniprot.txt
Mitochondrial isozyme of C-1-tetrahydrofolate synthase. The
GO:0035999 folate cycle
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA (FOLSYN-PWY-1); correct.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0035999 folate cycle
RCA
GO_REF:0000123
ACCEPT
Summary: YeastPathways RCA (PWY-2201); correct.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0046417 chorismate metabolic process
RCA
GO_REF:0000123
REMOVE
Summary: YeastPathways RCA inherited from the superpathway of chorismate metabolism (ALL-CHORISMATE-PWY-1), which bundles folate one-carbon reactions with chorismate-derived pathways. Mis1 interconverts one-carbon THF derivatives and does not act on chorismate or any chorismate-derived intermediate.
Reason: Superpathway inflation; C1-THF synthase does not participate in chorismate metabolism.
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0046655 folic acid metabolic process
RCA
GO_REF:0000123
MODIFY
Summary: YeastPathways RCA from PWY3O-20 (folate polyglutamylation) to 'folic acid metabolic process', defined as reactions of folic acid itself (pteroylglutamic acid). Mis1 acts on reduced one-carbon THF derivatives; tetrahydrofolate interconversion is the correct term.
Reason: Wrong chemical entity (folic acid vs THF derivatives).
Proposed replacements: tetrahydrofolate interconversion
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0046655 folic acid metabolic process
RCA
GO_REF:0000123
MODIFY
Summary: YeastPathways RCA from PWY3O-697 (folate interconversions) to 'folic acid metabolic process', defined as reactions of folic acid itself (pteroylglutamic acid). Mis1 acts on reduced one-carbon THF derivatives; tetrahydrofolate interconversion is the correct term.
Reason: Wrong chemical entity (folic acid vs THF derivatives).
Proposed replacements: tetrahydrofolate interconversion
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
GO:0046656 folic acid biosynthetic process
IDA
PMID:3528153
Purification and characterization of a mitochondrial isozyme...
MODIFY
Summary: Shannon & Rabinowitz characterised the three C1-THF synthase activities of the mitochondrial isozyme. These interconvert one-carbon units already on THF (formate + THF to 10-formyl-THF to 5,10-methenyl-THF to 5,10-methylene-THF); none synthesises folic acid (pteroylglutamate) de novo, which in yeast is the Fol1/Fol2/Fol3 pathway. The experimental evidence is sound; only the process term is wrong.
Reason: The demonstrated activities are tetrahydrofolate interconversions, not folic acid biosynthesis.
Proposed replacements: tetrahydrofolate interconversion
Supporting Evidence:
PMID:3528153
catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
PMID:3528153
Synthetase, cyclohydrolase, and dehydrogenase activities in an ade3 deletion strain co-purify 4,000-fold to yield a single protein species

Core Functions

C-terminal 10-formyl-THF synthetase activity of the mitochondrial C1-THF synthase (formate + THF + ATP <-> 10-formyl-THF).

Supporting Evidence:
  • PMID:3528153
    catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
  • PMID:3528153
    Synthetase, cyclohydrolase, and dehydrogenase activities in an ade3 deletion strain co-purify 4,000-fold to yield a single protein species
  • PMID:3528153
    Cell fractionation experiments show that the isozyme, but not C1-tetrahydrofolate synthase, is localized in the mitochondria

N-terminal D/C domain: 5,10-methenyl-THF cyclohydrolase activity of mitochondrial C1-THF synthase.

Supporting Evidence:
  • PMID:3528153
    catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
  • PMID:3528153
    Synthetase, cyclohydrolase, and dehydrogenase activities in an ade3 deletion strain co-purify 4,000-fold to yield a single protein species

N-terminal D/C domain: NADP+-dependent 5,10-methylene-THF dehydrogenase activity of mitochondrial C1-THF synthase.

Supporting Evidence:
  • PMID:3528153
    catalyzes 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10-methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10-methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) activities
  • PMID:3528153
    Synthetase, cyclohydrolase, and dehydrogenase activities in an ade3 deletion strain co-purify 4,000-fold to yield a single protein species

References

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Suggested Questions for Experts

Q: In which net direction does Mis1 operate in vivo under different carbon and nitrogen sources (formate production from mitochondrial one-carbon units versus formate assimilation)?

Deep Research

SGD

(MIS1-deep-research-sgd.md)
SGD gene description for MIS1 (yeast) SGD

SGD gene description for MIS1 (yeast)

Mitochondrial C1-tetrahydrofolate synthase; involved in interconversion between different oxidation states of tetrahydrofolate (THF); provides activities of formyl-THF synthetase, methenyl-THF cyclohydrolase, and methylene-THF dehydrogenase

πŸ“š Additional Documentation

Notes

(MIS1-notes.md)

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