dld1

UniProt ID: O00087
Organism: Schizosaccharomyces pombe 972h-
Review Status: COMPLETE
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Gene Description

dld1 (SPAC1002.09c; UniProt O00087) encodes mitochondrial dihydrolipoyl dehydrogenase (lipoamide dehydrogenase, E3; EC 1.8.1.4), a homodimeric FAD-dependent disulfide oxidoreductase. It reoxidises the dihydrolipoyl arms of the E2 subunits of the pyruvate, 2-oxoglutarate and branched-chain 2-oxoacid dehydrogenase complexes, and of the H protein of the glycine cleavage system, passing electrons to NAD+. As the single shared E3, it links glycolysis to the TCA cycle, runs the TCA cycle itself, and supports branched-chain amino acid catabolism and mitochondrial one-carbon supply. It is mitochondrial in a genome-wide screen; catalytic function is assigned by orthology to S. cerevisiae LPD1.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004148 dihydrolipoyl dehydrogenase (NADH) activity
IBA
GO_REF:0000033 		ACCEPT
Summary: PAINT inference from characterised E3 orthologs (S. cerevisiae LPD1, human DLD, E. coli Lpd). dld1 is the single S. pombe E3; sound.
Supporting Evidence:
file:SCHPO/dld1/dld1-uniprot.txt
FUNCTION: Lipoamide dehydrogenase is a component of the alpha-ketoacid dehydrogenase complexes (By similarity).
file:SCHPO/dld1/dld1-uniprot.txt
DR NCBIfam; TIGR01350; lipoamide_DH; 1.
GO:0004148 dihydrolipoyl dehydrogenase (NADH) activity
IEA
GO_REF:0000120 		ACCEPT
Summary: EC 1.8.1.4 / RHEA:15045 InterPro mapping; consistent with the IBA.
Supporting Evidence:
file:SCHPO/dld1/dld1-uniprot.txt
DR NCBIfam; TIGR01350; lipoamide_DH; 1.
GO:0004148 dihydrolipoyl dehydrogenase (NADH) activity
ISO
GO_REF:0000024 		ACCEPT
Summary: Curator transfer from S. cerevisiae LPD1.
Supporting Evidence:
file:SCHPO/dld1/dld1-uniprot.txt
DR NCBIfam; TIGR01350; lipoamide_DH; 1.
GO:0005739 mitochondrion
HDA
PMID:16823372
ORFeome cloning and global analysis of protein localization ... 		ACCEPT
Summary: ORFeome YFP screen placed dld1 in mitochondria.
Supporting Evidence:
PMID:16823372
we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein.
GO:0005739 mitochondrion
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic inference; agrees with the HDA.
Supporting Evidence:
PMID:16823372
we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein.
GO:0005759 mitochondrial matrix
IC
GO_REF:0000036 		ACCEPT
Summary: Curator inference from glycine cleavage; the E3 component of all 2-oxoacid dehydrogenase complexes and the glycine cleavage system is matrix-localised.
Supporting Evidence:
file:SCHPO/dld1/dld1-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000305}.
GO:0005759 mitochondrial matrix
IEA
GO_REF:0000044 		ACCEPT
Summary: UniProt subcellular-location mapping.
Supporting Evidence:
file:SCHPO/dld1/dld1-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000305}.
GO:0005960 glycine cleavage complex
ISO
GO_REF:0000024 		ACCEPT
Summary: dld1 is the L protein shared with the glycine cleavage system (transfer from S. cerevisiae LPD1).
Supporting Evidence:
file:SCHPO/dld1/dld1-uniprot.txt
FUNCTION: Lipoamide dehydrogenase is a component of the alpha-ketoacid dehydrogenase complexes (By similarity).
GO:0006086 pyruvate decarboxylation to acetyl-CoA
ISO
GO_REF:0000024 		ACCEPT
Summary: E3 of the pyruvate dehydrogenase complex; transfer from S. cerevisiae LPD1, consistent with the shared E3 in all eukaryotes.
Supporting Evidence:
file:SCHPO/dld1/dld1-uniprot.txt
FUNCTION: Lipoamide dehydrogenase is a component of the alpha-ketoacid dehydrogenase complexes (By similarity).
GO:0006103 2-oxoglutarate metabolic process
IBA
GO_REF:0000033 		MODIFY
Summary: True but broad; the E3 acts in OGDH-catalysed 2-oxoglutarate decarboxylation.
Reason: Correct but general: the E3 takes part in 2-oxoglutarate metabolism by reoxidizing the lipoyl arm of the 2-oxoglutarate dehydrogenase E2 during oxidative decarboxylation of 2-oxoglutarate to succinyl-CoA. MODIFY to GO:0120551, as in the DLD and E. coli lpd reviews.
Supporting Evidence:
file:SCHPO/dld1/dld1-uniprot.txt
FUNCTION: Lipoamide dehydrogenase is a component of the alpha-ketoacid dehydrogenase complexes (By similarity).
GO:0016491 oxidoreductase activity
IEA
GO_REF:0000002 		MODIFY
Summary: Generic InterPro parent of the specific dihydrolipoyl dehydrogenase activity.
Reason: Too general; the specific activity is already annotated.
Supporting Evidence:
file:SCHPO/dld1/dld1-uniprot.txt
DR NCBIfam; TIGR01350; lipoamide_DH; 1.
GO:0016668 oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor
IEA
GO_REF:0000002 		MODIFY
Summary: InterPro-derived parent of dihydrolipoyl dehydrogenase activity.
Reason: Too general; the specific activity is already annotated.
Supporting Evidence:
file:SCHPO/dld1/dld1-uniprot.txt
DR NCBIfam; TIGR01350; lipoamide_DH; 1.
GO:0019464 glycine decarboxylation via glycine cleavage system
ISO
GO_REF:0000024 		ACCEPT
Summary: L protein reoxidises the H-protein dihydrolipoyl arm in glycine cleavage.
Supporting Evidence:
file:SCHPO/dld1/dld1-uniprot.txt
FUNCTION: Lipoamide dehydrogenase is a component of the alpha-ketoacid dehydrogenase complexes (By similarity).
GO:0045252 oxoglutarate dehydrogenase complex
IBA
GO_REF:0000033 		ACCEPT
Summary: E3 component of the 2-oxoglutarate dehydrogenase complex.
Supporting Evidence:
file:SCHPO/dld1/dld1-uniprot.txt
FUNCTION: Lipoamide dehydrogenase is a component of the alpha-ketoacid dehydrogenase complexes (By similarity).
GO:0045254 pyruvate dehydrogenase complex
ISO
GO_REF:0000024 		ACCEPT
Summary: E3 component of the pyruvate dehydrogenase complex.
Supporting Evidence:
file:SCHPO/dld1/dld1-uniprot.txt
FUNCTION: Lipoamide dehydrogenase is a component of the alpha-ketoacid dehydrogenase complexes (By similarity).
GO:0050660 flavin adenine dinucleotide binding
IBA
GO_REF:0000033 		ACCEPT
Summary: FAD binding is intrinsic to the dihydrolipoyl dehydrogenase catalytic cycle.
Reason: FAD is the tightly bound redox cofactor that the E3 reaction cycle uses (FAD to the redox-active disulfide to NAD+); FAD binding is accepted as an intrinsic part of the core catalytic function, consistently across the L-protein reviews of the module.
Supporting Evidence:
file:SCHPO/dld1/dld1-uniprot.txt
Note=Binds 1 FAD per subunit. {ECO:0000250};
GO:0050660 flavin adenine dinucleotide binding
IEA
GO_REF:0000002 		ACCEPT
Summary: FAD binding is intrinsic to the dihydrolipoyl dehydrogenase catalytic cycle.
Reason: FAD is the tightly bound redox cofactor that the E3 reaction cycle uses (FAD to the redox-active disulfide to NAD+); FAD binding is accepted as an intrinsic part of the core catalytic function, consistently across the L-protein reviews of the module.
Supporting Evidence:
file:SCHPO/dld1/dld1-uniprot.txt
Note=Binds 1 FAD per subunit. {ECO:0000250};

Core Functions

Shared E3 dihydrolipoyl dehydrogenase: reoxidises protein-bound dihydrolipoyl groups with NAD+ in the mitochondrial 2-oxoacid dehydrogenase complexes and glycine cleavage system.

Molecular Function:
dihydrolipoyl dehydrogenase (NADH) activity
Directly Involved In:
pyruvate decarboxylation to acetyl-CoA glycine decarboxylation via glycine cleavage system
Cellular Locations:
mitochondrial matrix
Supporting Evidence:
  • file:SCHPO/dld1/dld1-uniprot.txt
    FUNCTION: Lipoamide dehydrogenase is a component of the alpha-ketoacid dehydrogenase complexes (By similarity).
  • file:SCHPO/dld1/dld1-uniprot.txt
    DR NCBIfam; TIGR01350; lipoamide_DH; 1.
  • file:SCHPO/dld1/dld1-uniprot.txt
    Note=Binds 1 FAD per subunit. {ECO:0000250};
  • file:SCHPO/dld1/dld1-uniprot.txt
    SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000305}.
  • PMID:16823372
    we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein.

References

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