Annotations: 3CRK

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d3crka1	All alpha proteins	Bromodomain-like	alpha-ketoacid dehydrogenase kinase, N-terminal domain	alpha-ketoacid dehydrogenase kinase, N-terminal domain	automated matches	Norway rat (Rattus norvegicus ) [TaxId: 10116 ],	SCOPe (2.08)
A	d3crka2	Alpha and beta proteins (a+b)	ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase	ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase	alpha-ketoacid dehydrogenase kinase, C-terminal domain	automated matches	Norway rat (Rattus norvegicus ) [TaxId: 10116 ],	SCOPe (2.08)
B	d3crkb1	All alpha proteins	Bromodomain-like	alpha-ketoacid dehydrogenase kinase, N-terminal domain	alpha-ketoacid dehydrogenase kinase, N-terminal domain	automated matches	Norway rat (Rattus norvegicus ) [TaxId: 10116 ],	SCOPe (2.08)
B	d3crkb2	Alpha and beta proteins (a+b)	ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase	ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase	alpha-ketoacid dehydrogenase kinase, C-terminal domain	automated matches	Norway rat (Rattus norvegicus ) [TaxId: 10116 ],	SCOPe (2.08)
C	d3crkc_	All beta proteins	Barrel-sandwich hybrid	Single hybrid motif	Biotinyl/lipoyl-carrier proteins and domains	Lipoyl domain of dihydrolipoamide acetyltransferase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d3crkd_	All beta proteins	Barrel-sandwich hybrid	Single hybrid motif	Biotinyl/lipoyl-carrier proteins and domains	Lipoyl domain of dihydrolipoamide acetyltransferase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	GHKL (Gyrase Hsp90 Histidine Kinase MutL) domain-like	8037155	3000091	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	alpha-ketoacid dehydrogenase kinase N-terminal domain	8037152	3001773	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	alpha-ketoacid dehydrogenase kinase N-terminal domain	8037152	3001773	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	GHKL (Gyrase Hsp90 Histidine Kinase MutL) domain-like	8037155	3000091	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Single hybrid motif	8043101	3001880	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	BCDHK_Adom3	e3crkA2	A: alpha bundles	X: Bromodomain-like	H: alpha-ketoacid dehydrogenase kinase-N (From Topology)	T: alpha-ketoacid dehydrogenase kinase-N	F: BCDHK_Adom3	ECOD (1.6)
A	HATPase_c	e3crkA1	A: a+b two layers	X: ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase-like	H: ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase (From Topology)	T: ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase	F: HATPase_c	ECOD (1.6)
B	BCDHK_Adom3	e3crkB4	A: alpha bundles	X: Bromodomain-like	H: alpha-ketoacid dehydrogenase kinase-N (From Topology)	T: alpha-ketoacid dehydrogenase kinase-N	F: BCDHK_Adom3	ECOD (1.6)
B	HATPase_c	e3crkB3	A: a+b two layers	X: ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase-like	H: ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase (From Topology)	T: ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase	F: HATPase_c	ECOD (1.6)
C	Biotin_lipoyl	e3crkC1	A: a+b complex topology	X: alpha/beta-Hammerhead/Barrel-sandwich hybrid	H: alpha/beta-Hammerhead/Barrel-sandwich hybrid	T: Single hybrid motif	F: Biotin_lipoyl	ECOD (1.6)
D	Biotin_lipoyl	e3crkD1	A: a+b complex topology	X: alpha/beta-Hammerhead/Barrel-sandwich hybrid	H: alpha/beta-Hammerhead/Barrel-sandwich hybrid	T: Single hybrid motif	F: Biotin_lipoyl	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.20.140.20	Mainly Alpha	Up-down Bundle	Butyryl-CoA Dehydrogenase, subunit A	domain 3	CATH (4.3.0)
A	3.30.565.10	Alpha Beta	2-Layer Sandwich	Heat Shock Protein 90	Histidine kinase-like ATPase, C-terminal domain	CATH (4.3.0)
B	1.20.140.20	Mainly Alpha	Up-down Bundle	Butyryl-CoA Dehydrogenase, subunit A	domain 3	CATH (4.3.0)
B	3.30.565.10	Alpha Beta	2-Layer Sandwich	Heat Shock Protein 90	Histidine kinase-like ATPase, C-terminal domain	CATH (4.3.0)
C	2.40.50.100	Mainly Beta	Beta Barrel	OB fold (Dihydrolipoamide Acetyltransferase, E2P)	RNA polymerase II/Efflux pump adaptor protein, barrel-sandwich hybrid domain	CATH (4.3.0)
D	2.40.50.100	Mainly Beta	Beta Barrel	OB fold (Dihydrolipoamide Acetyltransferase, E2P)	RNA polymerase II/Efflux pump adaptor protein, barrel-sandwich hybrid domain	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF02518	Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase (HATPase_c)	Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase	This family represents the structurally related ATPase domains of histidine kinase, DNA gyrase B and HSP90.	Domain
A, B	PF10436	Mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase (BCDHK_Adom3)	Mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase	-	Family
C, D	PF00364	Biotin-requiring enzyme (Biotin_lipoyl)	Biotin-requiring enzyme	This family covers two Prosite entries, the conserved lysine residue binds biotin in one group and lipoic acid in the other. Note that the HMM does not currently recognise the Glycine cleavage system H proteins.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Pyruvate dehydrogenase [lipoamide] kinase isozyme 2, mitochondrial	pyruvate dehydrogenase (acetyl-transferring) kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding pyruvate dehydrogenase (acetyl-transferring) kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding identical protein binding protein binding protein homodimerization activity protein dimerization activity protein serine/threonine kinase activity protein-containing complex binding	cellular response to stimulus cellular response to nutrient levels response to nutrient levels cellular response to chemical stimulus response to stimulus response to chemical response to nutrient cellular response to nutrient cellular process monosaccharide metabolic process gluconeogenesis regulation of primary metabolic process organic substance metabolic process regulation of small molecule metabolic process cellular response to stimulus cellular response to nutrient levels response to nutrient levels cellular response to chemical stimulus response to stimulus response to chemical response to nutrient cellular response to nutrient cellular process monosaccharide metabolic process gluconeogenesis regulation of primary metabolic process organic substance metabolic process regulation of small molecule metabolic process organic substance biosynthetic process small molecule metabolic process regulation of carbohydrate metabolic process regulation of glucose metabolic process regulation of biosynthetic process carbohydrate metabolic process regulation of biological process small molecule biosynthetic process carbohydrate biosynthetic process biological regulation hexose metabolic process primary metabolic process monosaccharide biosynthetic process hexose biosynthetic process biosynthetic process regulation of gluconeogenesis metabolic process regulation of carbohydrate biosynthetic process regulation of metabolic process glucose metabolic process regulation of cellular process signaling signal transduction by p53 class mediator cell death intracellular signal transduction cell communication apoptotic signaling pathway intrinsic apoptotic signaling pathway by p53 class mediator signal transduction apoptotic process intrinsic apoptotic signaling pathway programmed cell death chemical homeostasis homeostatic process regulation of pH monoatomic ion homeostasis monoatomic cation homeostasis cellular response to oxidative stress response to oxygen-containing compound cellular response to chemical stress cellular response to oxygen-containing compound response to reactive oxygen species cellular response to reactive oxygen species response to oxidative stress cellular response to stress response to stress cellular response to nitrogen compound response to organic substance response to peptide hormone insulin receptor signaling pathway cell surface receptor protein tyrosine kinase signaling pathway cellular response to endogenous stimulus response to hormone cellular response to organic substance enzyme-linked receptor protein signaling pathway cellular response to hormone stimulus cell surface receptor signaling pathway response to endogenous stimulus response to organonitrogen compound cellular response to peptide hormone stimulus response to nitrogen compound cellular response to organonitrogen compound response to insulin cellular response to insulin stimulus regulation of signaling regulation of signal transduction regulation of intracellular signal transduction regulation of response to stimulus calcium-mediated signaling intracellular signaling cassette regulation of calcium-mediated signaling regulation of cell communication organonitrogen compound metabolic process protein phosphorylation phosphorylation cellular metabolic process peptidyl-serine modification peptidyl-serine phosphorylation macromolecule modification peptidyl-amino acid modification phosphate-containing compound metabolic process protein metabolic process macromolecule metabolic process protein modification process phosphorus metabolic process nucleoside bisphosphate metabolic process ribonucleoside bisphosphate biosynthetic process regulation of acyl-CoA biosynthetic process regulation of amide metabolic process oxoacid metabolic process nucleotide biosynthetic process regulation of lipid metabolic process organonitrogen compound biosynthetic process carbohydrate derivative metabolic process purine ribonucleotide biosynthetic process acetyl-CoA metabolic process organic acid metabolic process regulation of nucleotide biosynthetic process nucleobase-containing compound metabolic process ribonucleotide biosynthetic process cellular ketone metabolic process regulation of sulfur metabolic process regulation of nucleotide metabolic process regulation of phosphate metabolic process sulfur compound metabolic process thioester metabolic process regulation of nucleobase-containing compound metabolic process ribose phosphate biosynthetic process nucleoside phosphate metabolic process pyruvate metabolic process regulation of cellular ketone metabolic process amide biosynthetic process regulation of cellular metabolic process nucleotide metabolic process regulation of purine nucleotide metabolic process organic cyclic compound metabolic process sulfur compound biosynthetic process organophosphate biosynthetic process organic cyclic compound biosynthetic process nucleoside phosphate biosynthetic process regulation of fatty acid metabolic process cellular lipid metabolic process regulation of phosphorus metabolic process monocarboxylic acid metabolic process purine ribonucleotide metabolic process purine nucleotide biosynthetic process ribose phosphate metabolic process purine nucleoside bisphosphate metabolic process ribonucleoside bisphosphate metabolic process acetyl-CoA biosynthetic process from pyruvate thioester biosynthetic process cellular biosynthetic process purine nucleotide metabolic process acyl-CoA metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process purine-containing compound biosynthetic process acyl-CoA biosynthetic process purine nucleoside bisphosphate biosynthetic process regulation of acetyl-CoA biosynthetic process from pyruvate amide metabolic process carbohydrate derivative biosynthetic process regulation of purine nucleotide biosynthetic process fatty acid metabolic process nucleoside bisphosphate biosynthetic process carboxylic acid metabolic process nucleobase-containing compound biosynthetic process purine-containing compound metabolic process regulation of cellular biosynthetic process acetyl-CoA biosynthetic process organophosphate metabolic process lipid metabolic process glucose homeostasis carbohydrate homeostasis	membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle protein-containing complex catalytic complex oxidoreductase complex pyruvate dehydrogenase complex alpha-ketoacid dehydrogenase complex
C, D	Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial	acetyltransferase activity catalytic activity, acting on a protein acyltransferase activity dihydrolipoyllysine-residue acetyltransferase activity acyltransferase activity, transferring groups other than amino-acyl groups transferase activity S-acetyltransferase activity S-acyltransferase activity catalytic activity identical protein binding protein binding binding	aerobic respiration cellular respiration tricarboxylic acid cycle energy derivation by oxidation of organic compounds cellular metabolic process metabolic process cellular process primary metabolic process generation of precursor metabolites and energy nucleoside bisphosphate metabolic process ribonucleoside bisphosphate biosynthetic process oxoacid metabolic process nucleotide biosynthetic process organonitrogen compound biosynthetic process aerobic respiration cellular respiration tricarboxylic acid cycle energy derivation by oxidation of organic compounds cellular metabolic process metabolic process cellular process primary metabolic process generation of precursor metabolites and energy nucleoside bisphosphate metabolic process ribonucleoside bisphosphate biosynthetic process oxoacid metabolic process nucleotide biosynthetic process organonitrogen compound biosynthetic process carbohydrate derivative metabolic process purine ribonucleotide biosynthetic process acetyl-CoA metabolic process organic acid metabolic process nucleobase-containing compound metabolic process ribonucleotide biosynthetic process phosphate-containing compound metabolic process organic substance biosynthetic process small molecule metabolic process sulfur compound metabolic process thioester metabolic process phosphorus metabolic process ribose phosphate biosynthetic process nucleoside phosphate metabolic process pyruvate metabolic process amide biosynthetic process nucleotide metabolic process organic cyclic compound metabolic process sulfur compound biosynthetic process biosynthetic process organophosphate biosynthetic process organic cyclic compound biosynthetic process nucleoside phosphate biosynthetic process monocarboxylic acid metabolic process purine ribonucleotide metabolic process purine nucleotide biosynthetic process ribose phosphate metabolic process purine nucleoside bisphosphate metabolic process ribonucleoside bisphosphate metabolic process acetyl-CoA biosynthetic process from pyruvate thioester biosynthetic process cellular biosynthetic process purine nucleotide metabolic process organic substance metabolic process acyl-CoA metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process purine-containing compound biosynthetic process acyl-CoA biosynthetic process purine nucleoside bisphosphate biosynthetic process amide metabolic process carbohydrate derivative biosynthetic process organonitrogen compound metabolic process nucleoside bisphosphate biosynthetic process carboxylic acid metabolic process nucleobase-containing compound biosynthetic process purine-containing compound metabolic process acetyl-CoA biosynthetic process organophosphate metabolic process monosaccharide metabolic process carbohydrate metabolic process hexose metabolic process glucose metabolic process	membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle protein-containing complex catalytic complex oxidoreductase complex pyruvate dehydrogenase complex alpha-ketoacid dehydrogenase complex membrane-enclosed lumen membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle protein-containing complex catalytic complex oxidoreductase complex pyruvate dehydrogenase complex alpha-ketoacid dehydrogenase complex membrane-enclosed lumen mitochondrial matrix intracellular organelle lumen organelle lumen

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR003594	Histidine kinase/HSP90-like ATPase	Domain
A, B	IPR039028	PDK/BCKDK protein kinase	Family
A, B	IPR036784	Alpha-ketoacid/pyruvate dehydrogenase kinase, N-terminal domain superfamily	Homologous Superfamily
A, B	IPR036890	Histidine kinase/HSP90-like ATPase superfamily	Homologous Superfamily
A, B	IPR018955	Branched-chain alpha-ketoacid dehydrogenase kinase/Pyruvate dehydrogenase kinase, N-terminal	Domain
A, B	IPR005467	Histidine kinase domain	Domain
C, D	IPR001078	2-oxoacid dehydrogenase acyltransferase, catalytic domain	Domain
C, D	IPR045257	Dihydrolipoamide acetyltransferase/Pyruvate dehydrogenase protein X component	Family
C, D	IPR006257	Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex	Family
C, D	IPR023213	Chloramphenicol acetyltransferase-like domain superfamily	Homologous Superfamily
C, D	IPR036625	E3-binding domain superfamily	Homologous Superfamily
C, D	IPR004167	Peripheral subunit-binding domain	Domain
C, D	IPR011053	Single hybrid motif	Homologous Superfamily
C, D	IPR003016	2-oxo acid dehydrogenase, lipoyl-binding site	Binding Site
C, D	IPR000089	Biotin/lipoyl attachment	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
C, D	Pharos: P10515	pyruvate dehydrogenase E2 deficiency pyruvate dehydrogenase deficiency cirrhosis of liver drug-induced liver injury intellectual disability lung adenocarcinoma Mitochondrial Diseases osteosarcoma Pick disease coronary artery disease hereditary spastic paraplegia large cell medulloblastoma lung cancer myocardial ischemia ovarian cancer pyruvate dehydrogenase E2 deficiency pyruvate dehydrogenase deficiency cirrhosis of liver drug-induced liver injury intellectual disability lung adenocarcinoma Mitochondrial Diseases osteosarcoma Pick disease coronary artery disease hereditary spastic paraplegia large cell medulloblastoma lung cancer myocardial ischemia ovarian cancer dermatomyositis inborn errors of metabolism Leigh syndrome malignant mesothelioma non-small cell lung carcinoma pancreatic intraductal papillary-mucinous neoplasm

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.