DLST is the E2 (dihydrolipoyllysine-residue succinyltransferase, EC 2.3.1.61) core component of the mitochondrial 2-oxoglutarate (alpha-ketoglutarate) dehydrogenase complex (OGDHC), a megadalton enzyme of the tricarboxylic acid (TCA) cycle assembled from the E1 component OGDH, multiple copies of the DLST E2 core, and the shared E3 component DLD. Within the complex DLST carries a covalently attached lipoyl cofactor on an N-terminal lipoyl-binding domain; the lipoyl arm is succinylated by E1 during oxidative decarboxylation of 2-oxoglutarate, and DLST then transfers the succinyl group to coenzyme A to generate succinyl-CoA. The same DLST E2 core, together with the shared DLD E3, also serves the 2-oxoadipate dehydrogenase complex (OADHC) in which the DHTKD1 E1 oxidatively decarboxylates 2-oxoadipate; here DLST acts as a dihydrolipoyllysine-residue glutaryltransferase forming glutaryl-CoA in the final step of L-lysine (and L-tryptophan) catabolism via the saccharopine pathway. DLST is predominantly localized to the mitochondrial matrix. A small nuclear fraction of the 2-oxoglutarate dehydrogenase complex associates with the acetyltransferase KAT2A/GCN5 on chromatin and provides locally generated succinyl-CoA for histone H3 lysine succinylation. Germline loss-of-function variants in DLST cause an autosomal dominant pheochromocytoma/paraganglioma predisposition syndrome (PPGL7).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) assignment of DLST to the mitochondrion. DLST is the E2 component of the mitochondrial 2-oxoglutarate dehydrogenase complex and is predominantly a mitochondrial-matrix protein, consistent with its cleaved N-terminal mitochondrial transit peptide (residues 1-67). Reason: Correct and well supported by the IBA panel and by direct experimental evidence for mitochondrial localization of DLST and the OGDH complex. Supporting Evidence: PMID:30929736 DLST encodes the E2 subunit of the mitochondrial Ξ±KG dehydrogenase (OGDH) complex |
| GO:0004149 dihydrolipoyllysine-residue succinyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) assignment of the core molecular function of DLST, the E2 succinyltransferase (EC 2.3.1.61) of the 2-oxoglutarate dehydrogenase complex. DLST transfers the succinyl group from its dihydrolipoyl arm to coenzyme A to form succinyl-CoA. This is the central, defining function of the gene. Reason: This is the core catalytic function of DLST, confirmed by the IBA panel, by human catalytic-activity/active-site data (His424), and by the well-understood OGDHC reaction mechanism. Supporting Evidence: PMID:36854377 E2o transfers the succinyl functional group from its LD domain onto CoA-SH generating succinyl-CoA PMID:30929736 The OGDH complex catalyzes the overall conversion of Ξ±KG to succinyl-CoA and CO |
| GO:0006099 tricarboxylic acid cycle | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) assignment of DLST to the TCA cycle. As the E2 of the 2-oxoglutarate dehydrogenase complex, DLST catalyzes the succinyl-transfer step of the cycle; the complex functions directly within the TCA cycle. Reason: Core biological process for DLST, strongly supported by the IBA panel and by direct experimental evidence. Supporting Evidence: PMID:36854377 OGDHC functions directly within the TCA cycle metabolizing 2-oxoglutarate to succinyl-CoA, CO2 and NADH + H+ in three consecutive steps |
| GO:0004149 dihydrolipoyllysine-residue succinyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated (IEA) assignment of the core succinyltransferase molecular function via InterPro/RHEA/EC (EC 2.3.1.61, RHEA:15213). Redundant with the experimental IMP, IBA, and ISS annotations of the same term. Reason: Correct core function; the EC/RHEA mapping matches the experimentally established DLST catalytic activity. Supporting Evidence: PMID:30929736 DLST encodes the E2 subunit of the mitochondrial Ξ±KG dehydrogenase (OGDH) complex |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Automated import (IEA) from the UniProt Subcellular Location vocabulary (SL-0191, Nucleus). DLST is predominantly a mitochondrial-matrix protein; only a small (~1-1.6%) nuclear fraction of the OGDH complex exists, where it supports KAT2A-dependent histone succinylation. Reason: The nuclear pool is real but minor and moonlighting rather than the core mitochondrial function; keep as a non-core localization. Verified experimentally by KAT2A/histone-succinylation work. Supporting Evidence: PMID:29211711 about 1β1.6% of total OGDH, DLST, and DLD was localized in the nucleus |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000120 | ACCEPT | Summary: Automated (IEA) assignment to the mitochondrial matrix, the principal compartment where DLST acts as the E2 core of the OGDH complex. Reason: Correct and specific core localization; consistent with UniProt subcellular location and the soluble matrix-localized nature of the OGDH complex. Supporting Evidence: PMID:30929736 DLST encodes the E2 subunit of the mitochondrial Ξ±KG dehydrogenase (OGDH) complex |
| GO:0006099 tricarboxylic acid cycle | IEA GO_REF:0000120 | ACCEPT | Summary: Automated (IEA) assignment of DLST to the TCA cycle. Redundant with the experimental IMP and phylogenetic IBA annotations of the same term. Reason: Core biological process; correct and consistent with experimental evidence. Supporting Evidence: PMID:36854377 OGDHC functions directly within the TCA cycle metabolizing 2-oxoglutarate to succinyl-CoA, CO2 and NADH + H+ in three consecutive steps |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO (IEA) mapping from the 2-oxoacid dehydrogenase acyltransferase domain (IPR001078) to the generic parent term acyltransferase activity. The specific child term dihydrolipoyllysine-residue succinyltransferase activity (GO:0004149) is already annotated with experimental and phylogenetic evidence. Reason: Not wrong but uninformatively general; the precise molecular function (GO:0004149, and GO:0120571 for the OADHC role) is established. Generalize/replace with the specific succinyltransferase activity term. Proposed replacements: dihydrolipoyllysine-residue succinyltransferase activity Supporting Evidence: PMID:36854377 E2o transfers the succinyl functional group from its LD domain onto CoA-SH generating succinyl-CoA |
| GO:0045252 oxoglutarate dehydrogenase complex | IEA GO_REF:0000120 | ACCEPT | Summary: Automated (IEA) assignment of DLST as part of the oxoglutarate dehydrogenase complex. DLST is the E2 core-forming subunit of this complex. Reason: Correct and central; redundant with the experimental IDA and NAS annotations of the same term. Supporting Evidence: PMID:30929736 DLST encodes the E2 subunit of the mitochondrial Ξ±KG dehydrogenase (OGDH) complex |
| GO:0005515 protein binding | IPI PMID:16169070 A human protein-protein interaction network: a resource for ... | MARK AS OVER ANNOTATED | Summary: IntAct-derived IPI for a binary interaction (with NAP1L1, P55209) from a large-scale automated yeast two-hybrid human interactome screen. The bare term protein binding conveys no specific molecular function. Reason: A single high-throughput Y2H interaction with a nucleosome-assembly protein does not define an informative molecular function for DLST; the term protein binding is uninformative and this interaction has no established functional role. DLST's biologically meaningful partners (OGDH, DLD, KAT2A) are captured by complex and process terms. Supporting Evidence: PMID:16169070 We identified 3186 mostly novel interactions among 1705 proteins, resulting in a large, highly connected network. |
| GO:0005515 protein binding | IPI PMID:29128334 A Map of Human Mitochondrial Protein Interactions Linked to ... | MARK AS OVER ANNOTATED | Summary: IntAct-derived IPI(s) for interactions detected in an affinity-purification mass-spectrometry map of mitochondrial protein interactions (partners include CDK1, PSMC4, NAP1L1, YWHAE). The bare term protein binding conveys no specific molecular function. Reason: High-throughput AP/MS interactions do not establish an informative molecular function; protein binding is uninformative per curation guidelines. No specific functional consequence for DLST is established for these partners. Supporting Evidence: PMID:29128334 we report a high-confidence MP network including 1,964 interactions among 772 proteins (>90% previously unreported) |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: IntAct-derived IPIs for numerous (~70) binary interactions from a neurodegenerative-disease yeast two-hybrid interactome map. The bare term protein binding conveys no specific molecular function, and the interactors span many unrelated proteins. Reason: A large set of high-throughput Y2H interactions with functionally unrelated proteins does not define an informative molecular function; protein binding is uninformative per curation guidelines. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0120551 2-oxoglutarate decarboxylation to succinyl-CoA | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl-orthology (IEA) assignment to the specific process by which the 2-oxoglutarate dehydrogenase complex converts 2-oxoglutarate to succinyl-CoA. This is precisely the OGDHC reaction in which DLST performs the succinyl-transfer step. Reason: Accurate and specific process term for the OGDHC step catalyzed by DLST; well supported by the reaction mechanism. Supporting Evidence: PMID:36854377 OGDHC functions directly within the TCA cycle metabolizing 2-oxoglutarate to succinyl-CoA, CO2 and NADH + H+ in three consecutive steps |
| GO:0120571 dihydrolipoyllysine-residue glutaryltransferase activity | IDA PMID:29191460 The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogen... | ACCEPT | Summary: Experimental (IDA) demonstration that the shared DLST E2 (hE2o), together with the shared DLD E3, functions in the 2-oxoadipate dehydrogenase complex assembled with the DHTKD1 E1 (hE1a). In this complex DLST acts as a glutaryltransferase, transferring the glutaryl group to CoA to form glutaryl-CoA in L-lysine/L-tryptophan catabolism. Reason: A genuine, distinct molecular function of the same DLST E2 core when serving the OADHC; experimentally reconstituted with recombinant human components. Supporting Evidence: PMID:29191460 The hE1a has recruited the PMID:29191460 specific to the 2-oxoadipate dehydrogenase complex |
| GO:0005739 mitochondrion | NAS PMID:36854377 MRPS36 provides a structural link in the eukaryotic 2-oxoglu... | ACCEPT | Summary: ComplexPortal (NAS) assignment of DLST to the mitochondrion as a subunit of the mitochondrial 2-oxoglutarate dehydrogenase complex. Reason: Correct; the mitochondrial-matrix term (GO:0005759) is more specific but this parent localization is accurate. Supporting Evidence: PMID:36854377 which in eukaryotes are located within mitochondria |
| GO:0006099 tricarboxylic acid cycle | NAS PMID:36854377 MRPS36 provides a structural link in the eukaryotic 2-oxoglu... | ACCEPT | Summary: ComplexPortal (NAS) assignment of DLST to the TCA cycle as the E2 of the 2-oxoglutarate dehydrogenase complex. Redundant with the IBA and IMP annotations of the same term. Reason: Core biological process; correct and well supported. Supporting Evidence: PMID:36854377 OGDHC functions directly within the TCA cycle metabolizing 2-oxoglutarate to succinyl-CoA, CO2 and NADH + H+ in three consecutive steps |
| GO:0006103 2-oxoglutarate metabolic process | NAS PMID:36854377 MRPS36 provides a structural link in the eukaryotic 2-oxoglu... | ACCEPT | Summary: ComplexPortal (NAS) assignment of DLST to 2-oxoglutarate metabolic process. The OGDH complex consumes 2-oxoglutarate, converting it to succinyl-CoA; DLST is the succinyl-transfer subunit of that reaction. Reason: Accurate process term for the OGDHC substrate; consistent with the succinyl-CoA generating reaction. Also supported by the ISS annotation of the same term. Supporting Evidence: PMID:36854377 which generates NADH by oxidative decarboxylation |
| GO:0045252 oxoglutarate dehydrogenase complex | NAS PMID:36854377 MRPS36 provides a structural link in the eukaryotic 2-oxoglu... | ACCEPT | Summary: ComplexPortal (NAS) assignment of DLST as part of the oxoglutarate dehydrogenase complex. This paper defines the eukaryotic OGDHC architecture with the E2o (DLST) octahedral core. Redundant with the IDA and IEA annotations of the same term. Reason: Correct and central; DLST forms the core of this complex. Supporting Evidence: PMID:36854377 an octahedral core of 24 E2o subunits |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Human Protein Atlas immunofluorescence (IDA) localization to the nucleoplasm. DLST is predominantly mitochondrial; only a small nuclear fraction of the OGDH complex exists, where it supports histone succinylation. Reason: The nuclear/nucleoplasmic pool is genuine but minor and moonlighting, not the core function; retain as a non-core localization. Independently supported by focused KAT2A/histone-succinylation work. Supporting Evidence: PMID:29211711 about 1β1.6% of total OGDH, DLST, and DLD was localized in the nucleus |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: High-throughput proteomics (HTP) placing DLST in the mitochondrion as part of a quantitative high-confidence human mitochondrial proteome. Reason: Correct core localization; consistent with the mitochondrial-matrix E2 role of DLST. Supporting Evidence: PMID:34800366 Quantitative high-confidence human mitochondrial proteome |
| GO:0160167 oxoadipate dehydrogenase complex | IDA PMID:29191460 The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogen... | ACCEPT | Summary: Experimental (IDA) demonstration that the shared DLST E2 (hE2o) is part of the 2-oxoadipate dehydrogenase complex, assembled with the DHTKD1 E1 (hE1a) and the shared DLD E3. This is the second complex served by the same DLST E2 core. Reason: A genuine second complex membership for DLST, biochemically reconstituted; distinct from the OGDHC and central to L-lysine/L-tryptophan catabolism. Supporting Evidence: PMID:29191460 The hE1a has recruited the PMID:29191460 specific to the 2-oxoadipate dehydrogenase complex |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-9858321 | ACCEPT | Summary: Reactome (TAS) mitochondrial-matrix localization tied to the 2-oxoadipate dehydrogenase (DHTKD1) decarboxylation reaction, where DLST acts as the E2 of the OADHC. The matrix is the correct core localization. Reason: Correct and specific core localization for the OADHC/OGDHC E2 core. Supporting Evidence: file:human/DLST/DLST-uniprot.txt Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-9858590 | ACCEPT | Summary: Reactome (TAS) mitochondrial-matrix localization tied to the reaction in which DLST transfers the glutaryl group to CoA in the OADHC. The matrix is the correct core localization. Reason: Correct and specific core localization for the OADHC/OGDHC E2 core. Supporting Evidence: file:human/DLST/DLST-uniprot.txt Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-71401 | ACCEPT | Summary: Reactome (TAS) mitochondrial-matrix localization tied to the OGDH-catalyzed decarboxylation of 2-oxoglutarate within the OGDH complex. The matrix is the correct core localization. Reason: Correct and specific core localization for the OGDHC E2 core. Supporting Evidence: file:human/DLST/DLST-uniprot.txt Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-9853499 | ACCEPT | Summary: Reactome (TAS) mitochondrial-matrix localization tied to the DLD-catalyzed re-oxidation of the dihydrolipoyl arm within the OGDH complex. The matrix is the correct core localization. Reason: Correct and specific core localization for the OGDHC E2 core. Supporting Evidence: file:human/DLST/DLST-uniprot.txt Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-9853512 | ACCEPT | Summary: Reactome (TAS) mitochondrial-matrix localization for the reaction in which DLST transfers the succinyl group to CoA within the OGDH complex. The matrix is the correct core localization. Reason: Correct and specific core localization for the OGDHC E2 core. Supporting Evidence: file:human/DLST/DLST-uniprot.txt Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-9858589 | ACCEPT | Summary: Reactome (TAS) mitochondrial-matrix localization tied to the DLD-catalyzed re-oxidation step in the OADHC. The matrix is the correct core localization. Reason: Correct and specific core localization for the OADHC/OGDHC E2 core. Supporting Evidence: file:human/DLST/DLST-uniprot.txt Mitochondrion matrix |
| GO:0004149 dihydrolipoyllysine-residue succinyltransferase activity | IMP PMID:30929736 Recurrent Germline DLST Mutations in Individuals with Multip... | ACCEPT | Summary: Experimental (IMP) support for the core succinyltransferase activity from functional evaluation of DLST variants, including the catalytically essential active site His424 (H424A abolishes activity) and the disease-associated p.Gly374Glu that compromises DLST function and disrupts OGDH complex activity. Reason: Directly establishes the core catalytic molecular function of human DLST in cells; UniProt cites this paper for EC 2.3.1.61 and active-site His424. Supporting Evidence: PMID:30929736 Depletion of any of the OGDH complex subunits leads to impaired enzymatic activity and Ξ±KG accumulation, and it has been demonstrated that DLST is a non-redundant member of the OGDH complex. |
| GO:0006099 tricarboxylic acid cycle | IMP PMID:30929736 Recurrent Germline DLST Mutations in Individuals with Multip... | ACCEPT | Summary: Experimental (IMP) support for DLST involvement in the TCA cycle. DLST-KO cells exhibit complete disruption of the oxidative TCA cycle, and DLST variants disrupt OGDH complex activity and cause TCA-cycle metabolite (2HG) accumulation. Reason: Core biological process, directly demonstrated by loss-of-function studies in cells. Supporting Evidence: PMID:30929736 they exhibit a complete disruption of the oxidative TCA cycle |
| GO:0016746 acyltransferase activity | IMP PMID:30929736 Recurrent Germline DLST Mutations in Individuals with Multip... | MODIFY | Summary: Experimental (IMP) annotation to the generic parent term acyltransferase activity. The specific molecular function, dihydrolipoyllysine-residue succinyltransferase activity (GO:0004149), is annotated with the same experimental evidence. Reason: Correct in essence but uninformatively general; the precise succinyltransferase activity is the appropriate term. Generalize/replace with GO:0004149. Proposed replacements: dihydrolipoyllysine-residue succinyltransferase activity Supporting Evidence: PMID:30929736 Depletion of any of the OGDH complex subunits leads to impaired enzymatic activity and Ξ±KG accumulation, and it has been demonstrated that DLST is a non-redundant member of the OGDH complex. |
| GO:0004149 dihydrolipoyllysine-residue succinyltransferase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity (ISS) transfer of the core succinyltransferase activity from an ortholog. Redundant with the human IMP, IBA, and IEA annotations of the same term. Reason: Correct core function, independently confirmed experimentally in human DLST. Supporting Evidence: PMID:36854377 E2o transfers the succinyl functional group from its LD domain onto CoA-SH generating succinyl-CoA |
| GO:0005634 nucleus | IDA PMID:29211711 KAT2A coupled with the Ξ±-KGDH complex acts as a histone H3 s... | KEEP AS NON CORE | Summary: Experimental (IDA) nuclear localization of DLST as part of the Ξ±-KGDH complex. Cell fractionation and immunofluorescence showed ~1-1.6% of DLST (and OGDH, DLD) in the nucleus, where the complex couples with KAT2A for histone succinylation; DLST NLS residues Arg224/Lys226 mediate nuclear translocation. Reason: A genuine but minor moonlighting localization; the core function of DLST is mitochondrial. Retain as non-core. Supporting Evidence: PMID:29211711 about 1β1.6% of total OGDH, DLST, and DLD was localized in the nucleus |
| GO:0005739 mitochondrion | IDA PMID:29211711 KAT2A coupled with the Ξ±-KGDH complex acts as a histone H3 s... | ACCEPT | Summary: Experimental (IDA) mitochondrial localization of DLST. The bulk (~98%) of the Ξ±-KGDH complex, including DLST, resides in the mitochondrion. Reason: Correct core localization; the mitochondrial-matrix term is more specific but this is accurate. Supporting Evidence: PMID:29211711 which is a component of the Ξ±-KGDH complex that catalyses the conversion of Ξ±-ketoglutarate (Ξ±-KG) to succinyl- CoA |
| GO:0006103 2-oxoglutarate metabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity (ISS) transfer of 2-oxoglutarate metabolic process. DLST, as the OGDHC E2, consumes 2-oxoglutarate in producing succinyl-CoA. Redundant with the NAS annotation of the same term. Reason: Accurate process term for the OGDHC substrate; consistent with experimental evidence. Supporting Evidence: PMID:36854377 which generates NADH by oxidative decarboxylation |
| GO:0006104 succinyl-CoA metabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity (ISS) transfer of succinyl-CoA metabolic process. The product of the DLST-catalyzed reaction is succinyl-CoA, so DLST directly participates in succinyl-CoA metabolism. Reason: Accurate process term for the product of the DLST succinyltransferase reaction. Supporting Evidence: PMID:36854377 E2o transfers the succinyl functional group from its LD domain onto CoA-SH generating succinyl-CoA |
| GO:0045252 oxoglutarate dehydrogenase complex | IDA PMID:29211711 KAT2A coupled with the Ξ±-KGDH complex acts as a histone H3 s... | ACCEPT | Summary: Experimental (IDA) demonstration that DLST is part of the Ξ±-KGDH (OGDH) complex, shown by co-immunoprecipitation of endogenous OGDH, DLST, and DLD. Redundant with the NAS and IEA annotations of the same term. Reason: Correct and central complex membership, directly demonstrated in human cells. Supporting Evidence: PMID:29211711 which is a component of the Ξ±-KGDH complex that catalyses the conversion of Ξ±-ketoglutarate (Ξ±-KG) to succinyl- CoA |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-5694018 | ACCEPT | Summary: Reactome (TAS) mitochondrial-matrix localization tied to a lipoyl/glycine- cleavage-system oxidation reaction. The matrix is the correct core localization for DLST. Reason: Correct and specific core localization. Supporting Evidence: file:human/DLST/DLST-uniprot.txt Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-6792572 | ACCEPT | Summary: Reactome (TAS) mitochondrial-matrix localization tied to LIPT1-mediated lipoyl transfer onto DBT/DLST (lipoylation of the E2 lipoyl domain). The matrix is the correct core localization for DLST. Reason: Correct and specific core localization; consistent with DLST lipoylation in the matrix. Supporting Evidence: file:human/DLST/DLST-uniprot.txt Mitochondrion matrix |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: High-throughput proteomics (HDA) placing DLST in a membrane fraction from a study defining the NK-cell membrane proteome. DLST is a soluble mitochondrial-matrix enzyme with no transmembrane region. Reason: DLST has no membrane domain and is a soluble matrix protein; a membrane-fraction co-purification does not reflect a genuine membrane localization. This is a proteomic-survey artifact and not a core (or accurate) localization. Supporting Evidence: PMID:19946888 Defining the membrane proteome of NK cells. file:human/DLST/DLST-uniprot.txt Mitochondrion matrix |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | KEEP AS NON CORE | Summary: High-throughput proteomics (HDA) detecting DLST in a human sperm nucleus proteome. A genuine nuclear pool of DLST/the OGDH complex exists (per focused KAT2A work), but this HDA is a proteomic-survey localization in a specialized cell type. Reason: The nuclear pool of DLST is real but minor and moonlighting; retain as non-core rather than as a defining localization. Independently supported by KAT2A/histone- succinylation work. Supporting Evidence: PMID:29211711 about 1β1.6% of total OGDH, DLST, and DLD was localized in the nucleus |
| GO:0006091 generation of precursor metabolites and energy | TAS PMID:8009371 Isolation, characterization, and mapping of gene encoding di... | MARK AS OVER ANNOTATED | Summary: Author-statement (TAS) annotation to the broad process generation of precursor metabolites and energy, from the cloning/mapping paper for the human E2k (dihydrolipoyl succinyltransferase) of the alpha-ketoglutarate dehydrogenase complex. This reflects the TCA-cycle role but at a very general level. Reason: Not wrong but uninformatively broad; the specific processes (tricarboxylic acid cycle, 2-oxoglutarate metabolic process, 2-oxoglutarate decarboxylation to succinyl-CoA) are already annotated with better evidence. Supporting Evidence: PMID:8009371 alpha-ketoglutarate dehydrogenase complex (KGDHC) from a human fetal brain cDNA |
| GO:0019477 L-lysine catabolic process | IDA PMID:29191460 The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogen... | NEW | Summary: Proposed annotation capturing DLST's role in L-lysine catabolism. As the E2 of the 2-oxoadipate dehydrogenase complex (with the DHTKD1 E1 and shared DLD E3), DLST carries out the final glutaryl-transfer step of the saccharopine pathway of L-lysine (and L-tryptophan) degradation, forming glutaryl-CoA. UniProt records this pathway (L-lysine degradation via saccharopine; glutaryl-CoA from L-lysine, step 6/6) and the shared-E2 function was demonstrated experimentally. Reason: DLST participates in lysine catabolism via its shared role in the 2-oxoadipate dehydrogenase complex; this process is supported by UniProt PATHWAY and by experimental reconstitution of the OADHC, and is not otherwise represented in the existing annotations. This row originally proposed GO:0033512 (L-lysine catabolic process to acetyl-CoA via L-saccharopine), which is obsolete in the GO release 2026-07-26 with replaced_by GO:0019477; the saccharopine route is recorded in the summary and core description. Supporting Evidence: PMID:29191460 specific to the 2-oxoadipate dehydrogenase complex file:human/DLST/DLST-uniprot.txt Amino-acid degradation; L-lysine degradation via saccharopine |
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