kgd4

UniProt ID: G2TRP3
Organism: Schizosaccharomyces pombe 972h-
Review Status: DRAFT
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Gene Description

kgd4 (ymr31; SPBC21B10.14; UniProt G2TRP3) encodes the fungal-type alpha-ketoglutarate dehydrogenase subunit 4 (Kgd4/MRPS36 family), an adaptor that recruits the E3 dihydrolipoyl dehydrogenase (dld1) to the E1-E2 core of the mitochondrial 2-oxoglutarate dehydrogenase complex. Function is assigned by orthology to S. cerevisiae Kgd4.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005739 mitochondrion
IEA
GO_REF:0000044
ACCEPT
Summary: UniProt SubCell vocabulary mapping of the curated SUBCELLULAR LOCATION comment (Mitochondrion), which UniProt assigns by similarity to S. cerevisiae Kgd4 (P19955); consistent with the predicted N-terminal mitochondrial transit peptide and with membership of the mitochondrial OGDC.
Supporting Evidence:
file:SCHPO/kgd4/kgd4-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P19955}.
file:SCHPO/kgd4/kgd4-uniprot.txt
Belongs to the alpha-ketoglutarate dehydrogenase component 4 family.
GO:0005739 mitochondrion
ISS
GO_REF:0000024
ACCEPT
Summary: Mitochondrial location by similarity to S. cerevisiae Kgd4 (P19955); the curated UniProt SUBCELLULAR LOCATION comment carries this by-similarity evidence, and kgd4 belongs to the Kgd4 family whose members are subunits of the mitochondrial OGDC.
Supporting Evidence:
file:SCHPO/kgd4/kgd4-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P19955}.
file:SCHPO/kgd4/kgd4-uniprot.txt
Belongs to the alpha-ketoglutarate dehydrogenase component 4 family.
GO:0005743 mitochondrial inner membrane
ISO
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: Transfer of inner-membrane location from bovine KGD4/MRPS36 (UniProtKB:P82908). The protein is an OGDC subunit in the mitochondrial matrix; the inner-membrane placement likely reflects the family's earlier assignment to the mitoribosome small subunit.
Reason: Action changed from KEEP_AS_NON_CORE to MARK_AS_OVER_ANNOTATED. No evidence places S. pombe kgd4 in the inner membrane: its own UniProt location is Mitochondrion, by similarity to S. cerevisiae Kgd4 (P19955), with no TM segment. Work on S. cerevisiae Kgd4 showed that this family, previously assigned to the mitochondrial ribosome small subunit, is instead a subunit of the alpha-ketoglutarate dehydrogenase complex, a matrix enzyme (PMID:25165143). The ISO source is the bovine ortholog (UniProtKB:P82908), whose inner-membrane annotations are Reactome TAS rows on mitochondrial translation reactions, so the inner-membrane sub-compartment looks over-propagated. Not REMOVE, since peripheral membrane contact of OGDC is not excluded.
Propagation Review
Root cause: SOURCE WEAK OR INFERRED
Failure modes: COMPARTMENT OR COMPLEX MISMATCH
Sources checked:
UniProtKB:P82908 Β· KGD4/MRPS36 (Bos taurus) SOURCE WEAK OR INFERRED
QuickGO lists the bovine GO:0005743 annotations only as Reactome TAS rows on mitochondrial translation reactions (R-BTA-5432387 and others), which treat the protein as a mitoribosome small-subunit component. That assignment was revised when the family was shown to be an OGDC subunit (PMID:25165143), so the inner-membrane location does not carry over to S. pombe kgd4.
Supporting Evidence:
PMID:25165143
This subunit is part of a conserved family of proteins that were previously annotated to be components of the small subunit of the mitochondrial ribosome.
PMID:25165143
Our data establish that these proteins instead play an important role in the organization of mitochondrial KGDH, because they are necessary for recruiting the E3 subunit to the E1-E2 core of the enzyme
GO:0006099 tricarboxylic acid cycle
ISO
GO_REF:0000024
ACCEPT
Summary: Transfer from the S. cerevisiae ortholog. The curated UniProt FUNCTION and SUBUNIT comments (by similarity to S. cerevisiae Kgd4, P19955) place kgd4 in the 2-oxoglutarate dehydrogenase complex, which catalyses the TCA-cycle conversion of 2-oxoglutarate to succinyl-CoA; kgd4 acts in the cycle as the assembly/adaptor subunit of that enzyme rather than as a catalytic subunit. No S. pombe experimental data.
Supporting Evidence:
file:SCHPO/kgd4/kgd4-uniprot.txt
Required for incorporation of the E3 subunit (dld1) into the E1-E2 core (kgd1-kgd2) of mitochondrial OGDC
file:SCHPO/kgd4/kgd4-uniprot.txt
Component of the 2-oxoglutarate dehydrogenase complex (OGDC),
GO:0006103 2-oxoglutarate metabolic process
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT inference; 2-oxoglutarate metabolism via the OGDH complex. Support is by similarity to S. cerevisiae Kgd4 (P19955) in the curated UniProt FUNCTION and SUBUNIT comments, plus Kgd4-family (PF10937) membership; kgd4 contributes as the E3-recruiting adaptor of OGDC, not as a catalytic subunit.
Supporting Evidence:
file:SCHPO/kgd4/kgd4-uniprot.txt
Required for incorporation of the E3 subunit (dld1) into the E1-E2 core (kgd1-kgd2) of mitochondrial OGDC
file:SCHPO/kgd4/kgd4-uniprot.txt
Component of the 2-oxoglutarate dehydrogenase complex (OGDC),
file:SCHPO/kgd4/kgd4-uniprot.txt
Pfam; PF10937; Kgd4-YMR31; 1.
GO:0006103 2-oxoglutarate metabolic process
IEA
GO_REF:0000002
ACCEPT
Summary: InterPro2GO mapping from the Kgd4/YMR-31 family (IPR020373); 2-oxoglutarate metabolism via the OGDH complex. Family membership (PF10937/IPR020373) and the curated by-similarity FUNCTION comment (S. cerevisiae Kgd4, P19955) support kgd4 as the E3-recruiting adaptor of OGDC.
Supporting Evidence:
file:SCHPO/kgd4/kgd4-uniprot.txt
Pfam; PF10937; Kgd4-YMR31; 1.
file:SCHPO/kgd4/kgd4-uniprot.txt
Required for incorporation of the E3 subunit (dld1) into the E1-E2 core (kgd1-kgd2) of mitochondrial OGDC
GO:0030674 protein-macromolecule adaptor activity
ISO
GO_REF:0000024
ACCEPT
Summary: Transfer from the Kgd4/MRPS36 ortholog (supporting entity mouse Q9CQX8); S. cerevisiae Kgd4 bridges the E3 (Lpd1) to the E1-E2 core. The curated UniProt FUNCTION and SUBUNIT comments, by similarity to S. cerevisiae Kgd4 (P19955), describe kgd4 as a molecular adapter that interacts with E3 via its N-terminus and with the E1-E2 core via its C-terminus. No S. pombe experimental data.
Supporting Evidence:
file:SCHPO/kgd4/kgd4-uniprot.txt
Molecular adapter that is necessary to a form a stable
file:SCHPO/kgd4/kgd4-uniprot.txt
Required for incorporation of the E3 subunit (dld1) into the E1-E2 core (kgd1-kgd2) of mitochondrial OGDC
file:SCHPO/kgd4/kgd4-uniprot.txt
Within OGDC, interacts (via N-terminus) with E3 subunit and (via C-terminus) with the complex core formed by E1 and E2 subunits.
GO:0045252 oxoglutarate dehydrogenase complex
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT inference: Kgd4 is a subunit of the OGDH complex. The curated UniProt SUBUNIT comment (by similarity to S. cerevisiae Kgd4, P19955) describes it as the assembly factor component of OGDC alongside kgd1, kgd2 and dld1, contacting E3 and the E1-E2 core.
Supporting Evidence:
file:SCHPO/kgd4/kgd4-uniprot.txt
Component of the 2-oxoglutarate dehydrogenase complex (OGDC),
file:SCHPO/kgd4/kgd4-uniprot.txt
Within OGDC, interacts (via N-terminus) with E3 subunit and (via C-terminus) with the complex core formed by E1 and E2 subunits.

Core Functions

Adaptor subunit recruiting E3 to the OGDH E1-E2 core.

Supporting Evidence:
  • file:SCHPO/kgd4/kgd4-uniprot.txt
    Molecular adapter that is necessary to a form a stable
  • file:SCHPO/kgd4/kgd4-uniprot.txt
    Required for incorporation of the E3 subunit (dld1) into the E1-E2 core (kgd1-kgd2) of mitochondrial OGDC
  • file:SCHPO/kgd4/kgd4-uniprot.txt
    Component of the 2-oxoglutarate dehydrogenase complex (OGDC),

References

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