mdh1

UniProt ID: Q9Y7R8
Organism: Schizosaccharomyces pombe 972h-
Review Status: DRAFT
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Gene Description

mdh1 (SPCC306.08c; UniProt Q9Y7R8) encodes mitochondrial NAD-dependent malate dehydrogenase (EC 1.1.1.37), which oxidises L-malate to oxaloacetate, the last step of the TCA cycle, regenerating oxaloacetate for citrate synthase. It is mitochondrial in a genome-wide screen.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0003824 catalytic activity
IEA
GO_REF:0000002
MODIFY
Summary: Generic InterPro-derived parent of the specific activity, which is already annotated.
Reason: Catalytic activity is correct but general. Mdh1 belongs to the MDH type 1 family (NCBIfam TIGR01772, eukaryotic/ gamma-proteobacterial MDH) and UniProt curates the NAD-dependent (S)-malate/oxaloacetate reaction; the activity rests on family membership, not an S. pombe enzyme assay. Refine to the specific descendant GO:0030060 L-malate dehydrogenase (NAD+) activity, which the gene already carries (IBA, IEA).
Supporting Evidence:
file:SCHPO/mdh1/mdh1-uniprot.txt
Reaction=(S)-malate + NAD(+) = oxaloacetate + NADH + H(+);
file:SCHPO/mdh1/mdh1-uniprot.txt
SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 1 family.
file:SCHPO/mdh1/mdh1-uniprot.txt
NCBIfam; TIGR01772; MDH_euk_gproteo; 1.
GO:0005737 cytoplasm
IBA
GO_REF:0000033
MODIFY
Summary: PAINT inference of cytoplasm; true in GO's sense (the mitochondrion is part of the cytoplasm) but general, since mdh1 is the mitochondrial-matrix isozyme.
Reason: The IBA node (PTN000166149) groups Mdh1 with mitochondrial MDHs such as human MDH2 (P40926) and mouse Mdh2, so the claim is not contested; in GO the mitochondrial matrix is part_of the mitochondrion, which is part_of the cytoplasm. Mdh1 carries a predicted mitochondrial transit peptide, and the S. pombe ORFeome localization study (PMID:16823372) places it in the mitochondrial matrix, so the correct-but-general cytoplasm term is refined to GO:0005759 mitochondrial matrix, which the gene already carries (IEA, ISS).
Propagation Review
Root cause: TERM SCOPING PROBLEM
Failure modes: GRANULARITY MISMATCH
Sources checked:
PANTHER:PTN000166149 SUPPORTS TRANSFER
Node includes mitochondrial MDHs (human MDH2 P40926, mouse Mdh2); the cytoplasm claim is true for Mdh1 but less specific than its mitochondrial-matrix location.
Proposed replacements: mitochondrial matrix
Supporting Evidence:
file:SCHPO/mdh1/mdh1-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000269|PubMed:16823372}.
file:SCHPO/mdh1/mdh1-uniprot.txt
FT TRANSIT 1..?
file:SCHPO/mdh1/mdh1-uniprot.txt
PANTHER; PTHR11540:SF73; MALATE DEHYDROGENASE, MITOCHONDRIAL; 1.
GO:0005739 mitochondrion
HDA
PMID:16823372
ORFeome cloning and global analysis of protein localization ...
ACCEPT
Summary: ORFeome YFP screen: mitochondrion.
Supporting Evidence:
PMID:16823372
we determined the localization of 4,431 proteins
GO:0005739 mitochondrion
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT inference of mitochondrial location.
Reason: Root organelle term kept per policy; the claim holds. UniProt curates a mitochondrial matrix location from the S. pombe ORFeome localization study (PubMed:16823372) and annotates an N-terminal mitochondrial transit peptide; the matrix sub-compartment is carried by the GO:0005759 rows.
Supporting Evidence:
file:SCHPO/mdh1/mdh1-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix
file:SCHPO/mdh1/mdh1-uniprot.txt
TRANSIT 1..?
GO:0005759 mitochondrial matrix
IEA
GO_REF:0000044
ACCEPT
Summary: Matrix location of this TCA enzyme (inference or mapping); consistent.
Reason: The SubCell mapping comes from UniProt's curated matrix location, which is tied to the S. pombe ORFeome localization study (PubMed:16823372); the entry also has a mitochondrial transit peptide.
Supporting Evidence:
file:SCHPO/mdh1/mdh1-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix
file:SCHPO/mdh1/mdh1-uniprot.txt
TRANSIT 1..?
GO:0005759 mitochondrial matrix
ISS
GO_REF:0000024
ACCEPT
Summary: Matrix location of this TCA enzyme (inference or mapping); consistent.
Reason: The ISS source is S. cerevisiae Mdh1 (P17505). The claim is independently supported for S. pombe by UniProt's curated matrix location from the ORFeome localization study (PubMed:16823372) and by the annotated mitochondrial transit peptide.
Supporting Evidence:
file:SCHPO/mdh1/mdh1-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix
file:SCHPO/mdh1/mdh1-uniprot.txt
TRANSIT 1..?
GO:0006099 tricarboxylic acid cycle
EXP
PMID:37164017
Optimization of energy production and central carbon metabol...
ACCEPT
Summary: 13C tracing in S. pombe versus S. japonicus shows that S. pombe runs a respiratory, oxidative TCA cycle (curator, full text).
Supporting Evidence:
PMID:37164017
Here, we use two related fission yeasts, Schizosaccharomyces pombe and Schizosaccharomyces japonicus, as a comparative model system.
PMID:37164017
We show that although S. japonicus does not respire oxygen, unlike S. pombe, it is capable of efficient NADH oxidation, amino acid synthesis, and ATP generation.
GO:0006099 tricarboxylic acid cycle
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT inference; TCA cycle step.
Reason: Mdh1 is a type 1 (mitochondrial-clade) malate dehydrogenase whose curated reaction, (S)-malate to oxaloacetate with NAD+, is the TCA-cycle step that regenerates oxaloacetate, and it is located in the matrix where the cycle runs. The enzyme activity rests on family classification and by-similarity active-site annotation, not on an S. pombe assay.
Supporting Evidence:
file:SCHPO/mdh1/mdh1-uniprot.txt
Reaction=(S)-malate + NAD(+) = oxaloacetate + NADH + H(+);
file:SCHPO/mdh1/mdh1-uniprot.txt
NCBIfam; TIGR01772; MDH_euk_gproteo; 1.
GO:0006099 tricarboxylic acid cycle
IEA
GO_REF:0000002
ACCEPT
Summary: InterPro/UniPathway mapping; consistent.
Reason: The mapping rests on IPR010097 (malate dehydrogenase type 1) membership; the family's reaction, (S)-malate to oxaloacetate with NAD+, is a TCA-cycle step, and the protein is in the mitochondrial matrix.
Supporting Evidence:
file:SCHPO/mdh1/mdh1-uniprot.txt
InterPro; IPR010097; Malate_DH_type1.
file:SCHPO/mdh1/mdh1-uniprot.txt
Reaction=(S)-malate + NAD(+) = oxaloacetate + NADH + H(+);
GO:0016491 oxidoreductase activity
IEA
GO_REF:0000002
MODIFY
Summary: Generic InterPro-derived parent of the specific activity, which is already annotated.
Reason: Oxidoreductase activity is correct but general. Mdh1 belongs to the MDH type 1 family (NCBIfam TIGR01772, eukaryotic/ gamma-proteobacterial MDH) and UniProt curates the NAD-dependent (S)-malate/oxaloacetate reaction; the activity rests on family membership, not an S. pombe enzyme assay. Refine to the specific descendant GO:0030060 L-malate dehydrogenase (NAD+) activity, which the gene already carries (IBA, IEA).
Supporting Evidence:
file:SCHPO/mdh1/mdh1-uniprot.txt
Reaction=(S)-malate + NAD(+) = oxaloacetate + NADH + H(+);
file:SCHPO/mdh1/mdh1-uniprot.txt
SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 1 family.
file:SCHPO/mdh1/mdh1-uniprot.txt
NCBIfam; TIGR01772; MDH_euk_gproteo; 1.
GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
IEA
GO_REF:0000002
MODIFY
Summary: Generic InterPro-derived parent of the specific activity, which is already annotated.
Reason: This CH-OH/NAD(P) oxidoreductase term is correct but general. Mdh1 belongs to the MDH type 1 family (NCBIfam TIGR01772, eukaryotic/ gamma-proteobacterial MDH) and UniProt curates the NAD-dependent (S)-malate/oxaloacetate reaction; the activity rests on family membership, not an S. pombe enzyme assay. Refine to the specific descendant GO:0030060 L-malate dehydrogenase (NAD+) activity, which the gene already carries (IBA, IEA).
Supporting Evidence:
file:SCHPO/mdh1/mdh1-uniprot.txt
Reaction=(S)-malate + NAD(+) = oxaloacetate + NADH + H(+);
file:SCHPO/mdh1/mdh1-uniprot.txt
SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 1 family.
file:SCHPO/mdh1/mdh1-uniprot.txt
NCBIfam; TIGR01772; MDH_euk_gproteo; 1.
GO:0030060 L-malate dehydrogenase (NAD+) activity
IBA
GO_REF:0000033
ACCEPT
Summary: NAD-malate dehydrogenase activity (PAINT/EC).
Reason: Supported by family membership (MDH type 1, NCBIfam TIGR01772 eukaryotic/gamma-proteobacterial MDH), UniProt's curated reaction, and a by-similarity proton-acceptor active site. No S. pombe enzyme assay is cached; the activity is inferred from the family.
Supporting Evidence:
file:SCHPO/mdh1/mdh1-uniprot.txt
Reaction=(S)-malate + NAD(+) = oxaloacetate + NADH + H(+);
file:SCHPO/mdh1/mdh1-uniprot.txt
SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 1 family.
file:SCHPO/mdh1/mdh1-uniprot.txt
NCBIfam; TIGR01772; MDH_euk_gproteo; 1.
GO:0030060 L-malate dehydrogenase (NAD+) activity
IEA
GO_REF:0000120
ACCEPT
Summary: NAD-malate dehydrogenase activity (PAINT/EC).
Reason: The EC/Rhea mapping derives from UniProt's curated reaction, which rests on MDH type 1 family membership (InterPro IPR010097) rather than an S. pombe assay.
Supporting Evidence:
file:SCHPO/mdh1/mdh1-uniprot.txt
Reaction=(S)-malate + NAD(+) = oxaloacetate + NADH + H(+);
file:SCHPO/mdh1/mdh1-uniprot.txt
InterPro; IPR010097; Malate_DH_type1.
GO:0043490 malate-aspartate shuttle
IC
GO_REF:0000111
KEEP AS NON CORE
Summary: Curator inference of the malate-aspartate shuttle; mitochondrial MDH is part of it in principle, but the shuttle has not been shown in S. pombe.
Reason: PomBase curator inference (IC from GO:0030060). The supporting facts are family-level and localization evidence, not a shuttle experiment in S. pombe; Mdh1 is an MDH type 1 enzyme catalysing the reversible NAD-dependent malate/oxaloacetate reaction and resides in the mitochondrial matrix (ORFeome localization, PMID:16823372), which is the matrix half of the malate-aspartate shuttle in other eukaryotes. Plausible but peripheral to its TCA-cycle role, so kept as non-core; the support is thin.
Supporting Evidence:
file:SCHPO/mdh1/mdh1-uniprot.txt
Reaction=(S)-malate + NAD(+) = oxaloacetate + NADH + H(+);
file:SCHPO/mdh1/mdh1-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000269|PubMed:16823372}.

Core Functions

Mitochondrial NAD-malate dehydrogenase, the last step of the TCA cycle.

Directly Involved In:
Cellular Locations:
Supporting Evidence:
  • file:SCHPO/mdh1/mdh1-uniprot.txt
    Reaction=(S)-malate + NAD(+) = oxaloacetate + NADH + H(+);
  • file:SCHPO/mdh1/mdh1-uniprot.txt
    SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 1 family.
  • file:SCHPO/mdh1/mdh1-uniprot.txt
    NCBIfam; TIGR01772; MDH_euk_gproteo; 1.
  • file:SCHPO/mdh1/mdh1-uniprot.txt
    SUBCELLULAR LOCATION: Mitochondrion matrix
  • PMID:16823372
    we determined the localization of 4,431 proteins

References

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