Gene Ontology annotation through association of InterPro records with GO terms
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
Human acyl-CoA dehydrogenase-9 plays a novel role in the mitochondrial beta-oxidation of unsaturated fatty acids.
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The abstract describes ACAD9 mitochondrial membrane association. That abstract sentence alone does not establish MCAD localization; the separate MCAD fractionation experiment in the full article is assessed in reference_review and the annotation reasons.
"Submitochondrial fractionation studies found native ACAD-9 to be associated with the mitochondrial membrane"
Prolonged moderate-intensity exercise without and with L-carnitine supplementation in patients with MCAD deficiency.
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Exercise raised plasma free fatty acids and octanoylcarnitine in MCAD-deficient patients. The authors interpret this as increased fatty-acid oxidation and suggest compensatory carnitine biosynthesis; these metabolite observations do not directly quantify successful MCAD reaction flux or establish ACADM catalysis of carnitine synthesis.
"A significant rise in plasma free fatty acids and octanoylcarnitine levels during exercise was seen in all patients, indicating a substantial increase in FAO during exercise"
Structural organization and regulatory regions of the human medium-chain acyl-CoA dehydrogenase gene.
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Describes the genomic organization and regulatory regions of the human ACADM gene; supports mitochondrial localization (TAS).
"Medium-chain acyl-CoA dehydrogenase (MCAD) is a highly regulated mitochondrial flavo-enzyme that catalyzes the initial reaction in fatty acid beta-oxidation"
Molecular characterization of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: identification of a lys329 to glu mutation in the MCAD gene, and expression of inactive mutant enzyme protein in E. coli.
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The human precursor Lys329Glu variant (mature K304E) produced inactive enzyme; impaired active-tetramer formation is offered as a probable explanation. Mature MCAD protein was detected within mitochondria.
"mutant MCAD, which was demonstrated to be inactive, probably because of the inability to form active tetrameric MCAD"
Protein misfolding is the molecular mechanism underlying MCADD identified in newborn screening.
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Wild-type recombinant human MCAD elutes as a homotetramer. The disease variants show heterogeneous defects in folding, assembly, stability or octanoyl-CoA kinetics, rather than one identical assembly defect in every variant.
"Wild-type MCAD was eluted in the tetrameric form with an almost negligible amount of aggregates"
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MCAD is an ACAD-family flavoprotein that catalyzes the first step of mitochondrial beta-oxidation of medium-chain fatty acids.
"MCAD is a member of the acyl-CoA dehydrogenase (ACAD) family of flavoproteins, which catalyzes the first step of the mitochondrial β-oxidation of medium-chain fatty acids"
Characterization of wild-type and an active site mutant of human medium chain acyl-CoA dehydrogenase after expression in Escherichia coli.
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Recombinant human MCAD is a yellow flavoprotein with stoichiometric FAD; the active-site glutamate (Glu376 mature numbering) is the catalytic proton-abstracting base, its mutation abolishing activity.
"The wild-type enzyme is a yellow protein due to the content of stoichiometric FAD and had a specific activity which is 50% of MCADH purified from pig kidney"
Identification and characterization of new long chain acyl-CoA dehydrogenases.
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Characterized the human ACAD family in cerebellum; MCAD was localized to the molecular layer and axons of specific neurons, supporting medium-chain dehydrogenase activity and neuronal expression.
"MCAD in the molecular layer and axons of specific neurons"
Proteomic characterization of the human sperm nucleus.
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The source of the ACADM nucleus HDA annotation reports a highly purified human sperm-nucleus proteome depleted of non-nuclear structures. The ACADM-specific identification was not independently recovered; neither genuine nuclear residence nor contamination is established by the accessible abstract alone.
"sperm nuclei were obtained through CTAB treatment and isolated to over 99.9% purity without any tail fragments, acrosome or mitochondria"
Identification of a common mutation in patients with medium-chain acyl-CoA dehydrogenase deficiency.
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Identified precursor Lys329Glu (mature K304E) in human MCAD-deficient fibroblast cultures. The reported 31 of 34 mutant alleles describe the sampled cohort, not a universal population frequency or a direct kinetic measurement.
"A single A to G nucleotide replacement which resulted in lysine329-to-glutamic acid329 substitution of the MCAD protein was identified in all cultures"
Human METTL20 is a mitochondrial lysine methyltransferase that targets the β subunit of electron transfer flavoprotein (ETFβ) and modulates its activity.
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MCAD is one of the ETF-dependent dehydrogenases; methylation of ETFβ by METTL20 reduces ETF's ability to receive electrons from MCAD, confirming MCAD operates via ETF in beta-oxidation.
"METTL20-mediated methylation of ETFβ in vitro reduced its ability to receive electrons from the medium chain acyl-CoA dehydrogenase and the glutaryl-CoA dehydrogenase"
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
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The source paper defines the MitoCoP mitochondrial proteome and supplies the existing ACADM HTP annotation. Its ACADM-specific supplementary identification was not independently re-extracted; the generic proteome-size statement is context, not gene-specific detection evidence.
"defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)"
Purification and properties of short chain acyl-CoA, medium chain acyl-CoA, and isovaleryl-CoA dehydrogenases from human liver.
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Purified human liver MCAD is a homotetramer with 1 FAD per subunit that converts octanoyl-CoA to 2-octenoyl-CoA using ETF as electron acceptor.
"The products of SCA dehydrogenase/butyryl-CoA, MCA dehydrogenase/octanoyl-CoA, and IV dehydrogenase/isovaleryl-CoA reactions were identified as crotonyl-CoA, 2-octenoyl-CoA, and 3-methylcrotonyl-CoA"
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Each of the purified dehydrogenases is a homotetramer (native MW ~178,000 for MCAD) using ETF or PMS as electron acceptor.
"They all utilized electron transfer flavoprotein (ETF) or phenazine methosulfate (PMS) as an electron acceptor"
Medium-long-chain chimeric human Acyl-CoA dehydrogenase: medium-chain enzyme with the active center base arrangement of long-chain Acyl-CoA dehydrogenase.
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The catalytic base of MCAD is Glu376 (mature numbering) on loop JK; its position (versus Glu255 on helix G in LCAD/IVD) is a key determinant of chain-length specificity, with native MCAD peaking at hexanoyl/octanoyl-CoA.
"The catalytically essential glutamate residue that initiates catalysis by abstracting the substrate alpha-hydrogen as H+ is located at position 376 (mature MCADH numbering) on loop JK in medium chain acyl-CoA dehydrogenase (MCADH)"
dehydrogenation of 4-cis-decenoyl-CoA to form 2-trans-4-cis-decadienoyl-CoA
Octanoyl-CoA+FAD => trans-Oct-2-enoyl-CoA+FADH2
Decanoyl-CoA+FAD => trans-Dec-2-enoyl-CoA+FADH2
UniProtKB P11310: ACADM human curated protein record
Disturbed hepatic carbohydrate management during high metabolic demand in medium-chain acyl-CoA dehydrogenase (MCAD)-deficient mice.