Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Automatic Gene Ontology annotation based on Rhea mapping
Combined Automated Annotation using Multiple IEA Methods
Biochemical characterization and crystal structure determination of human heart short chain L-3-hydroxyacyl-CoA dehydrogenase provide insights into catalytic mechanism.
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Human SCHAD is a homodimeric dehydrogenase characterized biochemically and by an NAD+-bound crystal structure; substrate docking, rather than a solved substrate complex, was used in this paper to investigate the catalytic mechanism.
"catalyzes the oxidation of the hydroxyl group of L-3-hydroxyacyl-CoA to a keto group, concomitant with the reduction of NAD+ to NADH"
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Substrate modeling supports His158 as a general base assisted by Glu170 in the paper’s mature-chain numbering; these correspond to His170 and Glu182 of the canonical Q16836 precursor.
"His 158 serves as a general base, abstracting a proton from the 3-OH group of the substrate"
Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase.
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Crystal structures of apo-, cofactor-, and substrate-bound forms reveal NAD+-binding domain shifting relative to the C-terminal domain; supports NAD+ binding and catalytic mechanism.
"significant shifting of the NAD(+)-binding domain relative to the C-terminal domain occurs in the ternary and substrate-bound complexes"
Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion.
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First report linking a fatty-acid-oxidation defect (SCHAD/HADH deficiency, P258L) to hyperinsulinism, establishing HADH's role in insulin-secretion regulation.
"This is the first defect in fatty acid beta-oxidation that has been associated with hyperinsulinism"
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The disease-causing P258L variant abolishes catalytic activity, directly tying HADH to the 3-hydroxyacyl-CoA dehydrogenase reaction.
"Expression studies showed that the P258L enzyme had no catalytic activity"
Reye-like syndrome resulting from novel missense mutations in mitochondrial medium- and short-chain l-3-hydroxy-acyl-CoA dehydrogenase.
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Expressed human variants D45G and Y214H (paper numbering; precursor D57G/Y226H) respectively alter NADH Km and abolish detectable activity. The reported patient lacked clinical evidence of hyperinsulinism, distinguishing this case from earlier HADH cases.
"This association suggests that there is a role for M/SCHAD in regulating the pancreatic secretion of insulin"
Mechanism of hyperinsulinism in short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency involves activation of glutamate dehydrogenase.
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Mouse Hadh deletion, protein interaction experiments and islet enzyme kinetics support inhibitory regulation of GDH by SCHAD. This study found amino-acid hypersensitivity without an altered glucose-stimulated response, including with added octanoate or palmitate.
"reflecting the loss of an inhibitory protein-protein interaction of SCHAD upon GDH"
Role of medium- and short-chain L-3-hydroxyacyl-CoA dehydrogenase in the regulation of body weight and thermogenesis.
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This mouse knockout study reports low glucose, elevated insulin and increased islet secretion in response to glucose or glucose plus palmitate. Its secretagogue response differs from the normal glucose response reported in PMID:20670938; both observations are retained.
"insulin secretion in response to glucose and glucose plus palmitate was elevated in isolated islets of knockout mice"
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Hadh knockout impairs adaptive thermogenesis and body-weight regulation under high-fat/cold conditions.
"SCHAD plays an important role in adaptive thermogenesis"
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SCHAD/HADH is highly expressed in pancreatic islets of Langerhans, consistent with a direct role in beta-cell function.
"in the islets of Langerhans within the pancreas"
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
Human short-chain L-3-hydroxyacyl-CoA dehydrogenase: cloning and characterization of the coding sequence.
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Original cloning of human SCHAD cDNA; encodes a 314-aa protein with a 12-residue mitochondrial import peptide; expressed in liver, kidney, pancreas, heart and skeletal muscle.
"Northern blot analysis reveals SCHAD mRNA to be expressed in liver, kidney, pancreas, heart and skeletal muscle"
(S)-3-Hydroxydodecanoyl-CoA+NAD => 3-Oxododecanoyl-CoA+NADH+H
(S)-Hydroxybutanoyl-CoA+NAD => Acetoacetyl-CoA+NADH+H
(S)-Hydroxyhexanoyl-CoA+NAD => 3-Oxohexanoyl-CoA+NADH+H
(S)-Hydroxyoctanoyl-CoA+NAD => 3-Oxooctanoyl-CoA+NADH+H
(S)-Hydroxydecanoyl-CoA+NAD => 3-Oxodecanoyl-CoA+NADH+H
CLPXP binds mitochondrial matrix proteins
LONP1 degrades mitochondrial matrix proteins
LONP1 binds mitochondrial matrix proteins
CLPXP degrades mitochondrial matrix proteins
Assay of L-3-hydroxyacyl-coenzyme A dehydrogenase with substrates of different chain lengths.
Fenofibrate improves insulin sensitivity in connection with intramuscular lipid content, muscle fatty acid-binding protein, and beta-oxidation in skeletal muscle.
Growth hormone and heart failure: oxidative stress and energetic metabolism in rats.
High intensity training-induced changes in skeletal muscle antioxidant enzyme activity.
Effects of streptozotocin diabetes, insulin treatment, and training on the diaphragm.
UniProtKB Q16836: hydroxyacyl-coenzyme A dehydrogenase, mitochondrial