DLAT

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004742 dihydrolipoyllysine-residue acetyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of the E2 acetyltransferase activity, the defining catalytic function of DLAT. Well supported by direct experimental data in human and orthologs. Reason: This is the core, defining molecular function of DLAT (EC 2.3.1.12) and is corroborated by IDA evidence in the same GOA set. Supporting Evidence: PMID:20160912 E2 then transfers the acetyl moiety to CoA forming acetyl-CoA.
GO:0005739 mitochondrion	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic assignment of mitochondrial localization. Correct but the more specific matrix term (GO:0005759) better captures where DLAT acts. Reason: Mitochondrion is a correct but general compartment; the mitochondrial matrix annotations are more informative for the core function. Supporting Evidence: file:human/DLAT/DLAT-uniprot.txt SUBCELLULAR LOCATION Mitochondrion matrix
GO:0006086 pyruvate decarboxylation to acetyl-CoA	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic assignment of the overall PDC process to which DLAT contributes the E2 acetyltransfer step. This is the core biological process for DLAT. Reason: DLAT catalyzes the E2 step of the pyruvate-to-acetyl-CoA conversion; this is its core process and is supported by multiple experimental annotations. Supporting Evidence: PMID:20160912 E2 then transfers the acetyl moiety to CoA forming acetyl-CoA.
GO:0045254 pyruvate dehydrogenase complex	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic assignment of DLAT as part of the PDC. DLAT (E2) forms the structural core of this complex. Reason: DLAT is the E2 core subunit of the PDC; this complex membership is central to its function and confirmed experimentally. Supporting Evidence: PMID:19240034 The human PDC is organized around a 60-meric
GO:0004742 dihydrolipoyllysine-residue acetyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (ARBA/InterPro/EC 2.3.1.12/RHEA:17017) assignment of the core E2 acetyltransferase activity. Consistent with the experimental annotations. Reason: Correctly maps the EC 2.3.1.12 catalytic activity that is DLAT's core function; the UniProt record carries the same EC/RHEA reaction. Supporting Evidence: PMID:20160912 E2 then transfers the acetyl moiety to CoA forming acetyl-CoA.
GO:0005759 mitochondrial matrix	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of mitochondrial matrix localization (UniProtKB-SubCell SL-0170). This is the compartment where DLAT and the PDC act. Reason: Matrix localization is the correct, specific compartment for DLAT and is stated in the UniProt SUBCELLULAR LOCATION field. Supporting Evidence: file:human/DLAT/DLAT-uniprot.txt SUBCELLULAR LOCATION Mitochondrion matrix
GO:0006086 pyruvate decarboxylation to acetyl-CoA	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of the core PDC process. Consistent with experimental annotations to the same term. Reason: Correct core process; duplicate of experimentally supported annotations. Supporting Evidence: PMID:20160912 E2 then transfers the acetyl moiety to CoA forming acetyl-CoA.
GO:0016746 acyltransferase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: InterPro2GO electronic assignment of the general acyltransferase parent term. Correct but far less specific than GO:0004742. Reason: This is a general parent of the specific dihydrolipoyllysine-residue acetyltransferase activity that DLAT enables; retained but not core, as the specific term is annotated. Supporting Evidence: PMID:9045657 Purified E2 had a high
GO:0045254 pyruvate dehydrogenase complex	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of PDC membership. Consistent with experimental complex annotations. Reason: Correct core complex membership; duplicate of experimentally supported annotations. Supporting Evidence: PMID:19240034 The human PDC is organized around a 60-meric
GO:0005515 protein binding	IPI PMID:17683942 Distinct structural mechanisms for inhibition of pyruvate de...	MODIFY	Summary: IntAct IPI capturing the DLAT(E2)-PDK3 interaction (lipoyl domain 2 in complex with pyruvate dehydrogenase kinase 3). A real, structurally characterized interaction, but the term itself is uninformative. Reason: The DLAT inner lipoyl domain (L2) binds PDK3 and stimulates its kinase activity, which is more informative than bare protein binding and matches the definition of protein serine/threonine kinase activator activity (binds to and increases the activity of a protein serine/threonine kinase). PDK3 phosphorylates serine residues of the E1alpha subunit, and GO places pyruvate dehydrogenase kinase activity (GO:0004740) under protein serine/threonine kinase activity (GO:0004674), so the Ser/Thr-specific child is used rather than GO:0030295. The cached records are abstract-only, but the PMC full text of PMID:15861126 (PMC1142596, Figure 1A-B) was checked: lipoylated L2 at saturating concentration stimulates human PDK3 activity about 12-fold in a direct kinase assay, and PMID:17683942 (PMC2871385) reports a PDK3-L2-radicicol structure and the same L2-stimulated basal PDK3 activity. Proposed replacements: protein serine/threonine kinase activator activity Supporting Evidence: PMID:15861126 L2 binding stimulates PDK3 activity PMID:17683942 scaffold-free PDK3 activity, similar to the inner lipoyl domain
GO:0005515 protein binding	IPI PMID:18206651 Binding of pyruvate dehydrogenase to the core of the human p...	REMOVE	Summary: IntAct IPI capturing the DLAT(E2)-PDHB (E1 beta) interaction. The E1 component binds the subunit-binding domain of E2. Real interaction, uninformative term. Reason: Bare protein binding is uninformative. The E1beta (PDHB) to E2 E1-binding-domain contact is a genuine subunit-assembly interaction within the pyruvate dehydrogenase complex, which is represented by the complex cellular-component annotations; the paper supports no more specific molecular function for DLAT. Removal does not mean the interaction is false. Supporting Evidence: PMID:18206651 (E1) is bound to the E1-binding domain of dihydrolipoamide acetyltransferase
GO:0005515 protein binding	IPI PMID:25525879 Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase...	REMOVE	Summary: IntAct IPI capturing the DLAT-SIRT4 interaction. SIRT4 is a lipoamidase that delipoylates DLAT to regulate PDC activity. Real interaction, uninformative term. Reason: Bare protein binding is uninformative. DLAT is the substrate in this interaction (SIRT4 lipoamidase removes the lipoyl cofactor from DLAT); the enzyme-substrate relationship belongs on the enzyme, and no more specific molecular function of DLAT is supported. Removal does not mean the interaction is false. Supporting Evidence: PMID:25525879 SIRT4 hydrolyzes lipoamide cofactors from the DLAT E2 component of the PDH complex, thereby inhibiting PDH activity
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: High-throughput affinity-capture interactome (BioPlex) IPI to PDK3. Real but uninformative bare protein-binding term. Reason: Bare protein binding from a proteome-scale interaction screen is uninformative as a molecular function, and the screen supports no more specific activity for DLAT. Removal does not mean the reported interaction is false. Supporting Evidence: file:human/DLAT/DLAT-uniprot.txt Interacts with PDK2 and PDK3
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: High-throughput proteome-scale interactome (BioPlex 3.0) IPI (PDHB/PDK3). Real but uninformative bare protein-binding term. Reason: Bare protein binding from a proteome-scale interaction screen is uninformative as a molecular function, and the screen supports no more specific activity for DLAT. Removal does not mean the reported interaction is false. Supporting Evidence: file:human/DLAT/DLAT-uniprot.txt Interacts with PDHB
GO:0042802 identical protein binding	IPI PMID:18184587 Extended polypeptide linkers establish the spatial architect...	KEEP AS NON CORE	Summary: IPI for DLAT self-association. E2 self-assembles into the 60-meric central core of the PDC, so identical protein binding (homo-oligomerization) is a genuine and informative structural property. Reason: DLAT self-assembles into the dodecahedral E2 core; identical protein binding captures this real structural oligomerization. Kept as a supporting structural annotation, non-core relative to the catalytic activity. Supporting Evidence: PMID:18184587 consisting of a central E2 core decorated by a shell of peripheral enzymes
GO:0042802 identical protein binding	IPI PMID:18184588 Structures of the human pyruvate dehydrogenase complex cores...	KEEP AS NON CORE	Summary: IPI for DLAT self-association based on cryo-EM of the human E2 core. E2 trimers assemble into the 60-meric dodecahedral inner core. Reason: Captures the genuine homo-oligomeric self-assembly of E2 into the PDC core. Kept as a supporting structural annotation, non-core relative to catalysis. Supporting Evidence: PMID:18184588 Dihydrolipoyl acetyltransferase (E2) is the central component of pyruvate
GO:0016407 acetyltransferase activity	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Ensembl-projected (from mouse ortholog) electronic assignment of the general acetyltransferase parent term. Correct but less specific than GO:0004742. Reason: General parent of the specific dihydrolipoyllysine-residue acetyltransferase activity; retained but not core because the specific term is annotated. Supporting Evidence: PMID:9045657 Purified E2 had a high
GO:0042867 pyruvate catabolic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl-projected electronic assignment of the general pyruvate catabolism process. Correct but broader than the specific pyruvate-to-acetyl-CoA process. Reason: A correct but more general process term; the specific pyruvate decarboxylation to acetyl-CoA (GO:0006086) is the core process annotation. Supporting Evidence: PMID:24534072 plays a key role in the conversion of pyruvate to
GO:0006086 pyruvate decarboxylation to acetyl-CoA	TAS Reactome:R-HSA-9861559	ACCEPT	Summary: Reactome TAS for the overall PDC reaction that synthesizes acetyl-CoA from pyruvate. Core process for DLAT as the E2 component. Reason: Correct core process, curated by Reactome and consistent with experimental evidence. Supporting Evidence: PMID:24534072 acetyl-CoA connecting glycolysis to the citric acid cycle
GO:0004742 dihydrolipoyllysine-residue acetyltransferase activity	TAS Reactome:R-HSA-9861667	ACCEPT	Summary: Reactome TAS for the DLAT-catalyzed transfer of the acetyl group from acetyllipoyl-lysine to CoA. This is the defining E2 reaction. Reason: Core catalytic function, curated by Reactome (DLAT trimer transfers acetyl to CoA) and consistent with the EC 2.3.1.12 reaction. Supporting Evidence: PMID:20160912 E2 then transfers the acetyl moiety to CoA forming acetyl-CoA.
GO:0005739 mitochondrion	NAS PMID:24534072 Component co-expression and purification of recombinant huma...	KEEP AS NON CORE	Summary: ComplexPortal NAS for mitochondrial localization. Correct but general compartment. Reason: Correct but general compartment; the mitochondrial matrix term is more informative for the core function. Supporting Evidence: PMID:24534072 The mammalian pyruvate dehydrogenase complex (PDC) is a
GO:0006086 pyruvate decarboxylation to acetyl-CoA	IDA PMID:24534072 Component co-expression and purification of recombinant huma...	ACCEPT	Summary: IDA from reconstituted recombinant human PDC (all five components co-expressed and lipoylated) demonstrating the functional pyruvate-to-acetyl-CoA reaction. Core process. Reason: Direct experimental support for DLAT participating in the core PDC reaction via a functional reconstituted complex. Supporting Evidence: PMID:24534072 plays a key role in the conversion of pyruvate to
GO:0045254 pyruvate dehydrogenase complex	IPI PMID:19240034 Subunit and catalytic component stoichiometries of an in vit...	ACCEPT	Summary: IPI from in vitro reconstitution and stoichiometry study establishing DLAT (E2p) as part of the 60-meric PDC core. Core complex membership. Reason: Direct evidence that DLAT (E2p) is a subunit of the PDC core; this is central to its function. Supporting Evidence: PMID:19240034 dihydrolipoyl transacetylase (E2p)
GO:0005739 mitochondrion	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: HPA immunofluorescence IDA for mitochondrial localization. Correct but general compartment. Reason: Correct mitochondrial localization by immunofluorescence; general compartment, with matrix being the more specific and informative term. Supporting Evidence: file:human/DLAT/DLAT-uniprot.txt GO:0005739; C:mitochondrion; IDA:HPA
GO:0005759 mitochondrial matrix	ISS GO_REF:0000024	ACCEPT	Summary: ISS transfer (from rat ortholog P08461) of mitochondrial matrix localization. Correct specific compartment where DLAT acts. Reason: Matrix is the correct, specific compartment for DLAT/PDC and is consistent with the UniProt SUBCELLULAR LOCATION field. Supporting Evidence: file:human/DLAT/DLAT-uniprot.txt SUBCELLULAR LOCATION Mitochondrion matrix
GO:0006086 pyruvate decarboxylation to acetyl-CoA	IDA PMID:20160912 Interaction of E1 and E3 components with the core proteins o...	ACCEPT	Summary: IDA from reconstitution/kinetic study of the human PDC (E1, E2, E3 components) supporting DLAT's role in the overall pyruvate-to-acetyl-CoA reaction. Core process. Reason: Direct experimental support for DLAT in the core PDC process via functional reconstitution and activity assays. Supporting Evidence: PMID:20160912 E2 then transfers the acetyl moiety to CoA forming acetyl-CoA.
GO:0004742 dihydrolipoyllysine-residue acetyltransferase activity	IDA PMID:9242632 Dihydrolipoamide dehydrogenase-binding protein of the human ...	ACCEPT	Summary: MGI-curated IDA for the E2 acetyltransferase activity, from a reconstitution study of the human PDC (E3BP/E2). Core catalytic function. The paper title foregrounds E3BP (protein X), but the full-text reconstitution work assays the E2 core; defer to curator. Reason: Direct experimental support for the defining E2 catalytic activity; consistent with other IDA/IEA/EC annotations to the same term. Supporting Evidence: PMID:9242632 spontaneously reconstituted the pyruvate dehydrogenase complex in the presence
GO:0006086 pyruvate decarboxylation to acetyl-CoA	IC PMID:9242632 Dihydrolipoamide dehydrogenase-binding protein of the human ...	ACCEPT	Summary: MGI-curated IC (from the GO:0004742 activity) that DLAT acts within the overall pyruvate-to-acetyl-CoA process via functional PDC reconstitution. Core process. Reason: Reasonable inference from the E2 catalytic activity to participation in the PDC process; consistent with the other process annotations. Supporting Evidence: PMID:9242632 spontaneously reconstituted the pyruvate dehydrogenase complex in the presence
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	KEEP AS NON CORE	Summary: High-throughput mitochondrial proteome study assigning DLAT to the mitochondrion. Correct but general compartment. Reason: Correct mitochondrial localization from a high-confidence proteome; general compartment, with matrix being the more specific term. Supporting Evidence: PMID:34800366 Quantitative high-confidence human mitochondrial proteome
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-203946	ACCEPT	Summary: Reactome TAS placing DLAT in the mitochondrial matrix (PDK phosphorylation of the PDC subunit E1 reaction). Correct specific compartment. Reason: Matrix is the correct, specific compartment for DLAT/PDC; curated by Reactome. Supporting Evidence: file:human/DLAT/DLAT-uniprot.txt SUBCELLULAR LOCATION Mitochondrion matrix
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-204169	ACCEPT	Summary: Reactome TAS placing DLAT in the mitochondrial matrix (PDP dephosphorylation reaction). Correct specific compartment. Reason: Matrix is the correct, specific compartment for DLAT/PDC; curated by Reactome. Supporting Evidence: file:human/DLAT/DLAT-uniprot.txt SUBCELLULAR LOCATION Mitochondrion matrix
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9858752	ACCEPT	Summary: Reactome TAS placing DLAT in the mitochondrial matrix (LIPT1 lipoyl transfer to DLAT reaction). Correct specific compartment. Reason: Matrix is the correct, specific compartment for DLAT/PDC; curated by Reactome. Supporting Evidence: file:human/DLAT/DLAT-uniprot.txt SUBCELLULAR LOCATION Mitochondrion matrix
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9861616	ACCEPT	Summary: Reactome TAS placing DLAT in the mitochondrial matrix (DLD dehydrogenation of dihydrolipoyl reaction). Correct specific compartment. Reason: Matrix is the correct, specific compartment for DLAT/PDC; curated by Reactome. Supporting Evidence: file:human/DLAT/DLAT-uniprot.txt SUBCELLULAR LOCATION Mitochondrion matrix
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9861626	ACCEPT	Summary: Reactome TAS placing DLAT in the mitochondrial matrix (SIRT4 delipoylation of DLAT reaction). Correct specific compartment. Reason: Matrix is the correct, specific compartment for DLAT/PDC; curated by Reactome. Supporting Evidence: file:human/DLAT/DLAT-uniprot.txt SUBCELLULAR LOCATION Mitochondrion matrix
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9861667	ACCEPT	Summary: Reactome TAS placing DLAT in the mitochondrial matrix (DLAT acetyl transfer to CoA reaction). Correct specific compartment. Reason: Matrix is the correct, specific compartment for DLAT/PDC; curated by Reactome. Supporting Evidence: file:human/DLAT/DLAT-uniprot.txt SUBCELLULAR LOCATION Mitochondrion matrix
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9861734	ACCEPT	Summary: Reactome TAS placing DLAT in the mitochondrial matrix (E1 decarboxylation transferring acetyl to DLAT reaction). Correct specific compartment. Reason: Matrix is the correct, specific compartment for DLAT/PDC; curated by Reactome. Supporting Evidence: file:human/DLAT/DLAT-uniprot.txt SUBCELLULAR LOCATION Mitochondrion matrix
GO:0004742 dihydrolipoyllysine-residue acetyltransferase activity	IDA PMID:20160912 Interaction of E1 and E3 components with the core proteins o...	ACCEPT	Summary: UniProt-curated IDA for the E2 acetyltransferase activity (catalytic activity and interaction with PDHB reported). Core catalytic function. Reason: Direct experimental support for the defining E2 catalytic activity; this is the source of the EC 2.3.1.12 assignment in UniProt. Supporting Evidence: PMID:20160912 E1 carries out the decarboxylation of pyruvate and reductive acetylation of the lipoyl moieties of E2
GO:0006099 tricarboxylic acid cycle	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: ISS transfer of "tricarboxylic acid cycle" involvement. DLAT/PDC feeds the TCA cycle by producing acetyl-CoA but the PDH reaction itself is not a step of the TCA cycle; this conflates an upstream feeder role with the cycle proper. Reason: DLAT is not a TCA-cycle enzyme. The PDC produces acetyl-CoA that enters the TCA cycle, but pyruvate decarboxylation to acetyl-CoA (GO:0006086) is a distinct process. This ISS is an over-annotation (the correct process is annotated separately). Not removed outright per policy; flagged. Supporting Evidence: PMID:24534072 acetyl-CoA connecting glycolysis to the citric acid cycle
GO:0045254 pyruvate dehydrogenase complex	IDA PMID:9242632 Dihydrolipoamide dehydrogenase-binding protein of the human ...	ACCEPT	Summary: MGI-curated IDA that DLAT (E2) is part of the reconstituted PDC. Core complex membership. Reason: Direct experimental support for DLAT as the E2 core subunit of the PDC. Supporting Evidence: PMID:9242632 is required for anchoring dihydrolipoamide dehydrogenase (E3) to the
GO:0004742 dihydrolipoyllysine-residue acetyltransferase activity	IDA PMID:9045657 Assembly and full functionality of recombinantly expressed d...	ACCEPT	Summary: MGI-curated IDA for the E2 acetyltransferase activity from recombinant, fully functional human E2 that assembled into the dodecahedral core and had high acetyltransferase activity. Core catalytic function. Reason: Direct experimental demonstration of DLAT's E2 acetyltransferase activity using purified, assembled recombinant human protein. Supporting Evidence: PMID:9045657 Purified E2 had a high
GO:0045254 pyruvate dehydrogenase complex	IDA PMID:25525879 Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase...	ACCEPT	Summary: UniProt-curated IDA (from the SIRT4/PDH study) that DLAT is the E2 component of the PDC. Core complex membership. Reason: Direct experimental support for DLAT as the E2 subunit forming the PDC catalytic core. Supporting Evidence: PMID:25525879 DLAT also has a structural role, constituting the PDH catalytic core
GO:0005739 mitochondrion	HDA PMID:20833797 Phosphoproteome analysis of functional mitochondria isolated...	KEEP AS NON CORE	Summary: High-throughput phosphoproteome analysis of isolated mitochondria assigning DLAT to the mitochondrion. Correct but general compartment. Reason: Correct mitochondrial localization from a mitochondrial phosphoproteome; general compartment, with matrix being the more specific term. Supporting Evidence: PMID:20833797 functional mitochondria isolated from resting
GO:0005515 protein binding	IPI PMID:15861126 Crystal structure of pyruvate dehydrogenase kinase 3 bound t...	MODIFY	Summary: IPI capturing the DLAT lipoyl-domain-2/PDK3 interaction (crystal structure of PDK3 bound to lipoyl domain 2). Real, structurally defined interaction, but uninformative bare term. Reason: The DLAT inner lipoyl domain (L2) binds PDK3 and stimulates its kinase activity, which is more informative than bare protein binding and matches the definition of protein serine/threonine kinase activator activity (binds to and increases the activity of a protein serine/threonine kinase). PDK3 phosphorylates serine residues of the E1alpha subunit, and GO places pyruvate dehydrogenase kinase activity (GO:0004740) under protein serine/threonine kinase activity (GO:0004674), so the Ser/Thr-specific child is used rather than GO:0030295. The cached records are abstract-only, but the PMC full text of PMID:15861126 (PMC1142596, Figure 1A-B) was checked: lipoylated L2 at saturating concentration stimulates human PDK3 activity about 12-fold in a direct kinase assay, and PMID:17683942 (PMC2871385) reports a PDK3-L2-radicicol structure and the same L2-stimulated basal PDK3 activity. Proposed replacements: protein serine/threonine kinase activator activity Supporting Evidence: PMID:15861126 with concomitant stimulated kinase activity PMID:15861126 L2 binding stimulates PDK3 activity
GO:0004742 dihydrolipoyllysine-residue acetyltransferase activity	NAS PMID:3191998 Nucleotide sequence of a cDNA for the dihydrolipoamide acety...	ACCEPT	Summary: NAS from the original human DLAT cDNA sequencing paper, assigning the dihydrolipoamide acetyltransferase (E2) identity/activity. Core function, historically established. Reason: The founding sequence report identifying DLAT as the E2 acetyltransferase of the human PDC; consistent with all later experimental evidence. Supporting Evidence: PMID:3191998 the dihydrolipoamide acetyltransferase
GO:0045254 pyruvate dehydrogenase complex	NAS PMID:3191998 Nucleotide sequence of a cDNA for the dihydrolipoamide acety...	ACCEPT	Summary: NAS from the original DLAT cDNA paper, assigning DLAT as a component of the human PDC. Core complex membership, historically established. Reason: The founding report describing DLAT as the E2 component of the human PDC; consistent with later experimental complex annotations. Supporting Evidence: PMID:3191998 human pyruvate dehydrogenase complex

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Notes

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