BCKDK

Summary: BCKDK catalyzes phosphorylation of protein serine residues.

Reason: The kinase-class assignment is sound. Protein serine kinase activity captures the demonstrated residue chemistry more precisely, while the separately retained BCKDH kinase annotations specify its principal substrate. Human patient-derived evidence and the ACLY biochemical study support this refinement (PMID:24449431; PMID:29779826).

Proposed replacements: protein serine kinase activity

Summary: BCKDK catalyzes phosphorylation of protein serine residues.

Reason: The kinase-class assignment is sound. Protein serine kinase activity captures the demonstrated residue chemistry more precisely, while the separately retained BCKDH kinase annotations specify its principal substrate. Human patient-derived evidence and the ACLY biochemical study support this refinement (PMID:24449431; PMID:29779826).

Proposed replacements: protein serine kinase activity

Summary: BCKDK catalyzes phosphorylation of protein serine residues.

Reason: The kinase-class assignment is sound. Protein serine kinase activity captures the demonstrated residue chemistry more precisely, while the separately retained BCKDH kinase annotations specify its principal substrate. Human patient-derived evidence and the ACLY biochemical study support this refinement (PMID:24449431; PMID:29779826).

Proposed replacements: protein serine kinase activity

Summary: The cited phosphatase chemistry belongs to PPM1K.

Reason: The inspected Results and kinase-assay Methods of PMID:29779826 assign phosphate transfer to BCKDK and dephosphorylation to PPM1K. Purified MBP-BDK transfers radiolabel from ATP to ACL; V5-tagged BCKDK phosphorylates human ACLY Ser455. The human BCKDK construct is identified in Methods, so this conclusion does not rely on the title, abstract or a different-species assumption. GO:0004722 requires hydrolytic removal of phosphate from protein serine/threonine. Assigning that opposite catalytic chemistry to BCKDK is inconsistent with the paper’s explicit enzyme attribution.

Summary: Conditional PDC phosphorylation is supported in a mouse PDK-deficient setting.

Reason: Retain the curator-provided IBA as a contextual activity. PMID:33773101 reports BCKDK-dependent PDHA1 phosphorylation and PDC regulation in mouse embryos/cells lacking PDK family function. The inspected experiments are genetic/cellular, not a purified human BCKDK-to-PDHA1 assay; normal-condition PDC control remains open. PTN000236514 placement could not be independently reconstructed, so neither donor count nor the principal BCKDH substrate is used to reject the assertion.

Summary: Retain the curated physical-interaction observation as non-core.

Reason: PMID:18985028 reports viral-host interaction mapping. The source IPI assertion is retained, with no specific substrate or regulatory mechanism inferred from generic protein binding. The publication context is compatible with an interaction record; its exact supplementary interaction entry was not independently rederived.

Summary: Retain the curated physical-interaction observation as non-core.

Reason: PMID:21988832 reports human liver interaction mapping. The source IPI assertion is retained, with no specific substrate or regulatory mechanism inferred from generic protein binding. The publication context is compatible with an interaction record; its exact supplementary interaction entry was not independently rederived. The cached record also lists an erratum whose bearing on this pair was not established.

Summary: Retain the curated physical-interaction observation as non-core.

Reason: PMID:28514442 reports BioPlex affinity-purification interaction mapping. The source IPI assertion is retained, with no specific substrate or regulatory mechanism inferred from generic protein binding. The publication context is compatible with an interaction record; its exact supplementary interaction entry was not independently rederived.

Summary: Retain the curated physical-interaction observation as non-core.

Reason: PMID:32296183 reports HuRI binary interaction mapping. The source IPI assertion is retained, with no specific substrate or regulatory mechanism inferred from generic protein binding. The publication context is compatible with an interaction record; its exact supplementary interaction entry was not independently rederived.

Summary: Retain the curated physical-interaction observation as non-core.

Reason: PMID:33961781 reports BioPlex affinity-purification interaction mapping. The source IPI assertion is retained, with no specific substrate or regulatory mechanism inferred from generic protein binding. The publication context is compatible with an interaction record; its exact supplementary interaction entry was not independently rederived.

Summary: ATP binding supplies the phosphate donor for BCKDK kinase catalysis.

Reason: ATP-dependent phosphorylation is intrinsic to the BCKDH-regulating kinase. Purified protein assays in PMID:29779826 support the nucleotide-dependent catalytic mechanism, consistent with the rat ortholog-based source assertion. This does not imply a separate ATPase function.

Summary: ATP binding supplies the phosphate donor for BCKDK kinase catalysis.

Reason: ATP-dependent phosphorylation is intrinsic to the BCKDH-regulating kinase. Purified protein assays in PMID:29779826 support the nucleotide-dependent catalytic mechanism, consistent with the rat ortholog-based source assertion. This does not imply a separate ATPase function.

Summary: Mitochondria are a principal site of BCKDK function.

Reason: The cited human muscle mitochondrial phosphoproteome study provides experimental compartment evidence. Its abstract and cached Discussion were read; the HTML extraction does not include the main Methods/Results or supplements. The curated protein-level assignment is retained consistently with independent BCKDH pathway evidence, without claiming to have rederived the specific proteomic entry.

Summary: Mitochondria are a principal site of BCKDK function.

Reason: The cited MitoCoP study maps a high-confidence human mitochondrial proteome. Its abstract was read; the curated protein-level assignment is consistent with independent BCKDH pathway evidence.

Summary: Mitochondria are a principal site of BCKDK function.

Reason: The phylogenetic location assertion agrees with independent human mitochondrial and pathway evidence. The target occurring among descendant experimental sources is expected in PAINT and is not circular evidence. The ancestral tree itself was not reconstructed.

Summary: Mitochondria are a principal site of BCKDK function.

Reason: The curated immunofluorescence-based source location agrees with the established mitochondrial BCKDH-regulating activity. No particular image was independently rescored.

Summary: Mitochondria are a principal site of BCKDK function.

Reason: The original structural study and separately inspected introductory text place BCKD and its regulatory kinase in the mitochondrial system; additional human proteomic evidence supports this compartment.

Summary: BCKDK regulates the BCKDH complex in the mitochondrial matrix.

Reason: The matrix location is consistent with the normal UniProt targeting/localization record, the BCKDH complex association, and the curated Reactome phosphorylation reaction. Cytosolic activity on another substrate does not invalidate this principal compartment.

Summary: BCKDK regulates the BCKDH complex in the mitochondrial matrix.

Reason: The matrix location is consistent with the normal UniProt targeting/localization record, the BCKDH complex association, and the curated Reactome phosphorylation reaction. Cytosolic activity on another substrate does not invalidate this principal compartment.

Summary: BCKDK regulates the BCKDH complex in the mitochondrial matrix.

Reason: The matrix location is consistent with the normal UniProt targeting/localization record, the BCKDH complex association, and the curated Reactome phosphorylation reaction. Cytosolic activity on another substrate does not invalidate this principal compartment.

Summary: BCKDK regulates the BCKDH complex in the mitochondrial matrix.

Reason: The matrix location is consistent with the normal UniProt targeting/localization record, the BCKDH complex association, and the curated Reactome phosphorylation reaction. Cytosolic activity on another substrate does not invalidate this principal compartment.

Summary: BCKDK inhibits branched-chain amino acid breakdown through BCKDHA phosphorylation.

Reason: BCKDK directly phosphorylates and inhibits BCKDHA; the BCKDH catalytic components execute the degradative reaction. Human BCKDK loss of function increases BCKDH activity and BCAA consumption (PMID:24449431). GO:0006550 denotes L-isoleucine catabolic process, whereas GO:0045763 captures the demonstrated negative regulation. Inspection of the official AmiGO GO:0045763 child hierarchy and GO:0009083 definition, together with targeted term-name searches on 2026-10-01, identified no branched-chain-specific negative-regulation term in the consulted ontology snapshot (AmiGO last loaded 2026-08-06). GO:0045763 is therefore retained as the verified available regulatory term, with the BCAA-specific mechanism stated explicitly here and in the core description. This does not imply regulation of every amino acid pathway. Search scope and access limits are recorded in the notes; the term choice does not rely on its occurrence in the source annotations.

Proposed replacements: negative regulation of amino acid metabolic process

Summary: BCKDK inhibits branched-chain amino acid breakdown through BCKDHA phosphorylation.

Reason: BCKDK directly phosphorylates and inhibits BCKDHA; the BCKDH catalytic components execute the degradative reaction. Human BCKDK loss of function increases BCKDH activity and BCAA consumption (PMID:24449431). GO:0006552 denotes L-leucine catabolic process, whereas GO:0045763 captures the demonstrated negative regulation. Inspection of the official AmiGO GO:0045763 child hierarchy and GO:0009083 definition, together with targeted term-name searches on 2026-10-01, identified no branched-chain-specific negative-regulation term in the consulted ontology snapshot (AmiGO last loaded 2026-08-06). GO:0045763 is therefore retained as the verified available regulatory term, with the BCAA-specific mechanism stated explicitly here and in the core description. This does not imply regulation of every amino acid pathway. Search scope and access limits are recorded in the notes; the term choice does not rely on its occurrence in the source annotations.

Proposed replacements: negative regulation of amino acid metabolic process

Summary: BCKDK inhibits branched-chain amino acid breakdown through BCKDHA phosphorylation.

Reason: BCKDK directly phosphorylates and inhibits BCKDHA; the BCKDH catalytic components execute the degradative reaction. Human BCKDK loss of function increases BCKDH activity and BCAA consumption (PMID:24449431). GO:0006574 denotes L-valine catabolic process, whereas GO:0045763 captures the demonstrated negative regulation. Inspection of the official AmiGO GO:0045763 child hierarchy and GO:0009083 definition, together with targeted term-name searches on 2026-10-01, identified no branched-chain-specific negative-regulation term in the consulted ontology snapshot (AmiGO last loaded 2026-08-06). GO:0045763 is therefore retained as the verified available regulatory term, with the BCAA-specific mechanism stated explicitly here and in the core description. This does not imply regulation of every amino acid pathway. Search scope and access limits are recorded in the notes; the term choice does not rely on its occurrence in the source annotations.

Proposed replacements: negative regulation of amino acid metabolic process

Summary: The spermatogenesis transfer requires more specific donor evidence.

Reason: The electronic source traces to rat Bckdk Q00972. The indexed abstract of rat mutant study PMID:27472223 (a follow-up lead, not a cached reference) describes infertility together with systemic BCAA depletion, but its abstract does not establish the specific spermatogenic step performed by BCKDK. The original donor annotation history and relevant full experimental context were not reconstructed. Preserve the assertion pending that check rather than treat a pleiotropic phenotype as a core biochemical function.

Summary: BCKDK-dependent ACLY phosphorylation can promote lipid synthesis.

Reason: The cited study demonstrates direct ACLY phosphorylation by BCKDK, including human ACLY Ser455, and increased lipogenesis after kinase expression in rat liver. Positive regulation of lipid biosynthetic process better states the kinase action; BCKDK does not itself synthesize lipids. Human protein chemistry and rat physiological experiments are distinct evidence components.

Proposed replacements: positive regulation of lipid biosynthetic process

Summary: BCKDK inhibits branched-chain amino acid breakdown through BCKDHA phosphorylation.

Reason: BCKDK directly phosphorylates and inhibits BCKDHA; the BCKDH catalytic components execute the degradative reaction. Human BCKDK loss of function increases BCKDH activity and BCAA consumption (PMID:24449431). GO:0009063 denotes amino acid catabolic process, whereas GO:0045763 captures the demonstrated negative regulation. Inspection of the official AmiGO GO:0045763 child hierarchy and GO:0009083 definition, together with targeted term-name searches on 2026-10-01, identified no branched-chain-specific negative-regulation term in the consulted ontology snapshot (AmiGO last loaded 2026-08-06). GO:0045763 is therefore retained as the verified available regulatory term, with the BCAA-specific mechanism stated explicitly here and in the core description. This does not imply regulation of every amino acid pathway. Search scope and access limits are recorded in the notes; the term choice does not rely on its occurrence in the source annotations.

Proposed replacements: negative regulation of amino acid metabolic process

Summary: BCKDK inhibits branched-chain amino acid breakdown through BCKDHA phosphorylation.

Reason: BCKDK directly phosphorylates and inhibits BCKDHA; the BCKDH catalytic components execute the degradative reaction. Human BCKDK loss of function increases BCKDH activity and BCAA consumption (PMID:24449431). GO:0009083 denotes degradation itself, whereas GO:0045763 captures the demonstrated negative regulation. Inspection of the official AmiGO GO:0045763 child hierarchy and GO:0009083 definition, together with targeted term-name searches on 2026-10-01, identified no branched-chain-specific negative-regulation term in the consulted ontology snapshot (AmiGO last loaded 2026-08-06). GO:0045763 is therefore retained as the verified available regulatory term, with the BCAA-specific mechanism stated explicitly here and in the core description. This does not imply regulation of every amino acid pathway. Search scope and access limits are recorded in the notes; the term choice does not rely on its occurrence in the source annotations.

Proposed replacements: negative regulation of amino acid metabolic process

Summary: BCKDK inhibits branched-chain amino acid breakdown through BCKDHA phosphorylation.

Reason: BCKDK directly phosphorylates and inhibits BCKDHA; the BCKDH catalytic components execute the degradative reaction. Human BCKDK loss of function increases BCKDH activity and BCAA consumption (PMID:24449431). GO:0009083 denotes degradation itself, whereas GO:0045763 captures the demonstrated negative regulation. Inspection of the official AmiGO GO:0045763 child hierarchy and GO:0009083 definition, together with targeted term-name searches on 2026-10-01, identified no branched-chain-specific negative-regulation term in the consulted ontology snapshot (AmiGO last loaded 2026-08-06). GO:0045763 is therefore retained as the verified available regulatory term, with the BCAA-specific mechanism stated explicitly here and in the core description. This does not imply regulation of every amino acid pathway. Search scope and access limits are recorded in the notes; the term choice does not rely on its occurrence in the source annotations.

Proposed replacements: negative regulation of amino acid metabolic process

Summary: BCKDK inhibits branched-chain amino acid breakdown through BCKDHA phosphorylation.

Reason: BCKDK directly phosphorylates and inhibits BCKDHA; the BCKDH catalytic components execute the degradative reaction. Human BCKDK loss of function increases BCKDH activity and BCAA consumption (PMID:24449431). GO:0009083 denotes degradation itself, whereas GO:0045763 captures the demonstrated negative regulation. Inspection of the official AmiGO GO:0045763 child hierarchy and GO:0009083 definition, together with targeted term-name searches on 2026-10-01, identified no branched-chain-specific negative-regulation term in the consulted ontology snapshot (AmiGO last loaded 2026-08-06). GO:0045763 is therefore retained as the verified available regulatory term, with the BCAA-specific mechanism stated explicitly here and in the core description. This does not imply regulation of every amino acid pathway. Search scope and access limits are recorded in the notes; the term choice does not rely on its occurrence in the source annotations.

Proposed replacements: negative regulation of amino acid metabolic process

Summary: BCKDK can regulate PDC in a PDK-deficient mouse context.

Reason: Retain the existing phylogenetic assertion as contextual. The primary mouse PDK-deficiency study (PMID:33773101) links BCKDK to PDHA1 phosphorylation, PDC activity and pyruvate flux. It does not establish universal human PDC control when PDKs are present. The actual PTN000236514 placement could not be inspected, and no inference of an erroneous ancestral transfer is made.

Summary: BCKDK can influence glucose metabolism through conditional PDC regulation.

Reason: Retain the existing phylogenetic assertion as contextual. The primary mouse PDK-deficiency study (PMID:33773101) links BCKDK to PDHA1 phosphorylation, PDC activity and pyruvate flux. It does not establish universal human PDC control when PDKs are present. The actual PTN000236514 placement could not be inspected, and no inference of an erroneous ancestral transfer is made.

Summary: BCKDK is an ATP-dependent protein serine kinase.

Reason: The broad kinase/phosphorus-transfer assertion is correct but does not identify the substrate class. Protein serine kinase activity captures demonstrated chemistry across BCKDHA and ACLY; the separately retained BCKDH kinase term captures the principal substrate.

Proposed replacements: protein serine kinase activity

Summary: BCKDK is an ATP-dependent protein serine kinase.

Reason: The broad kinase/phosphorus-transfer assertion is correct but does not identify the substrate class. Protein serine kinase activity captures demonstrated chemistry across BCKDHA and ACLY; the separately retained BCKDH kinase term captures the principal substrate.

Proposed replacements: protein serine kinase activity

Summary: BCKDK associates with the branched-chain ketoacid dehydrogenase complex.

Reason: The original paper’s selected introductory text explicitly separates the branched-chain complex from the alpha-ketoglutarate complex and places the regulatory BCKD kinase on the branched-chain E2 core. Current GO:0045252 names the alpha-ketoglutarate-to-succinyl-CoA complex. GO:0160157 instead names the branched-chain complex and allows associated regulatory proteins. The original association is therefore retained with the appropriate complex identity; this does not assign an E1/E2/E3 catalytic role to BCKDK. The rat donor Q00972 and original evidence are preserved. Its underlying donor annotation history was not reconstructed, so no particular propagation-error origin is asserted.

Proposed replacements: branched-chain alpha-ketoacid dehydrogenase complex

Summary: BCKDK associates with the branched-chain ketoacid dehydrogenase complex.

Reason: The original paper’s selected introductory text explicitly separates the branched-chain complex from the alpha-ketoglutarate complex and places the regulatory BCKD kinase on the branched-chain E2 core. Current GO:0045252 names the alpha-ketoglutarate-to-succinyl-CoA complex. GO:0160157 instead names the branched-chain complex and allows associated regulatory proteins. The original association is therefore retained with the appropriate complex identity; this does not assign an E1/E2/E3 catalytic role to BCKDK. The rat donor Q00972 and original evidence are preserved. Its underlying donor annotation history was not reconstructed, so no particular propagation-error origin is asserted.

Proposed replacements: branched-chain alpha-ketoacid dehydrogenase complex

Summary: BCKDK associates with the branched-chain ketoacid dehydrogenase complex.

Reason: The original paper’s selected introductory text explicitly separates the branched-chain complex from the alpha-ketoglutarate complex and places the regulatory BCKD kinase on the branched-chain E2 core. Current GO:0045252 names the alpha-ketoglutarate-to-succinyl-CoA complex. GO:0160157 instead names the branched-chain complex and allows associated regulatory proteins. The original association is therefore retained with the appropriate complex identity; this does not assign an E1/E2/E3 catalytic role to BCKDK. The normal cache remains abstract-only; the relevant original-paper Introduction was read separately in the author-uploaded manuscript linked under this reference. The Introduction on journal page 15865 is background evidence, not a new binding assay in that structural study.

Proposed replacements: branched-chain alpha-ketoacid dehydrogenase complex

Summary: BCKDK negatively regulates amino acid metabolism.

Reason: Its direct inhibitory phosphorylation of BCKDHA reduces flux through the BCKDH-dependent degradation of branched-chain amino acids. Human loss-of-function evidence supports the direction of the mouse-derived source inference.

Summary: BCKDH kinase activity is the principal molecular function of BCKDK.

Reason: BCKDK phosphorylates the E1 alpha subunit and inhibits the branched-chain ketoacid dehydrogenase complex. Human patient-derived kinase loss, direct biochemical phosphorylation and curated pathway evidence converge on this activity; the inhibitor study provides complementary biochemical/cellular evidence.

Summary: BCKDH kinase activity is the principal molecular function of BCKDK.

Reason: BCKDK phosphorylates the E1 alpha subunit and inhibits the branched-chain ketoacid dehydrogenase complex. Human patient-derived kinase loss, direct biochemical phosphorylation and curated pathway evidence converge on this activity; the inhibitor study provides complementary biochemical/cellular evidence.

Summary: BCKDH kinase activity is the principal molecular function of BCKDK.

Reason: BCKDK phosphorylates the E1 alpha subunit and inhibits the branched-chain ketoacid dehydrogenase complex. Human patient-derived kinase loss, direct biochemical phosphorylation and curated pathway evidence converge on this activity; the inhibitor study provides complementary biochemical/cellular evidence.

Summary: BCKDH kinase activity is the principal molecular function of BCKDK.

Reason: BCKDK phosphorylates the E1 alpha subunit and inhibits the branched-chain ketoacid dehydrogenase complex. Human patient-derived kinase loss, direct biochemical phosphorylation and curated pathway evidence converge on this activity; the inhibitor study provides complementary biochemical/cellular evidence.

Summary: BCKDK catalyzes protein serine phosphorylation.

Reason: The demonstrated BCKDHA and ACLY serine substrates support this molecular activity. It describes shared chemistry without assigning an unverified new substrate-specific EC number.

Summary: BCKDK catalyzes protein serine phosphorylation.

Reason: The demonstrated BCKDHA and ACLY serine substrates support this molecular activity. It describes shared chemistry without assigning an unverified new substrate-specific EC number.

Summary: BCKDK catalyzes protein serine phosphorylation.

Reason: The demonstrated BCKDHA and ACLY serine substrates support this molecular activity. It describes shared chemistry without assigning an unverified new substrate-specific EC number.