ACADSB

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003995 acyl-CoA dehydrogenase activity	IBA GO_REF:0000033	ACCEPT	Summary: The PAINT assertion captures the acyl-CoA dehydrogenase chemistry directly demonstrated for human SBCAD (PMID:7698750, PMID:11013134). Reason: The inherited broad activity is part of the core function. Greater specificity in GO:0003853 does not make this parent activity incidental. No target-specific catalytic loss contradicts the ancestral assertion; the tree and alignment were not independently reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000744030 SUPPORTS TRANSFER This ancestral acyl-CoA dehydrogenase assertion agrees with direct human substrate assays. The target among descendant evidence is legitimate experimental grounding, not circularity. Substrate differences among family members do not contradict the broad catalytic term.
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: PAINT mitochondrial localization agrees with import of human SBCAD precursor into isolated mitochondria (PMID:11013134). Reason: The mitochondrion is the site of the core catalytic function; the separately annotated matrix compartment provides additional resolution without making this annotation non-core. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000097586 SUPPORTS TRANSFER The traced ancestral mitochondrial assertion is consistent with direct import of human SBCAD. P45954 in the descendant evidence is expected for an experimentally characterized target. No loss of targeting is established; the full phylogeny was not independently reconstructed.
GO:0003853 short-chain 2-methyl fatty acyl-CoA dehydrogenase activity	IEA GO_REF:0000120	ACCEPT	Summary: The combined Rhea/EC mapping describes short-chain 2-methyl acyl-CoA dehydrogenation, including the physiological (S)-2-methylbutyryl-CoA reaction (PMID:7698750, PMID:11013134). Reason: The human reaction and patient biochemical defect directly support this core molecular function. The mapped isobutyryl side reaction is not evidence that ACADSB replaces ACAD8 in physiological valine degradation. Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:43780 SUPPORTS TRANSFER Cached human UniProt records 2-methylbutanoyl-CoA conversion to tiglyl-CoA; this reaction record leaves substrate stereochemistry unspecified. RHEA:44180 SUPPORTS TRANSFER The recorded isobutyryl-CoA reaction is within short 2-methyl acyl-CoA chemistry and is linked to the original human enzyme study. Relative activity is assay-dependent; it does not establish a principal valine-catabolic role. RHEA:48256 SUPPORTS TRANSFER This explicitly (2S)-2-methylbutanoyl-CoA reaction matches the core isoleucine-derived substrate, unlike the separate rat-inferred (2R) reaction in UniProt. EC:1.3.8.5 SUPPORTS TRANSFER The curated 2-methylacyl-CoA dehydrogenase assignment agrees with recombinant human assays and the patient-specific block.
GO:0003995 acyl-CoA dehydrogenase activity	IEA GO_REF:0000002	ACCEPT	Summary: The InterPro active-site signature supports acyl-CoA dehydrogenase activity, which is directly demonstrated for human ACADSB (PMID:7698750). Reason: This broad catalytic term describes the core chemistry. It does not transfer an untested substrate specificity from another family member. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR006089 SUPPORTS TRANSFER The matched acyl-CoA dehydrogenase conserved-site signature is consistent with experimentally retained catalytic activity in human SBCAD.
GO:0005739 mitochondrion	IEA GO_REF:0000117	ACCEPT	Summary: The ARBA mitochondrial prediction agrees with direct precursor-import evidence and curated matrix localization (PMID:11013134; UniProt:P45954). Reason: Mitochondrial localization is core biology. Acceptance rests on independent human evidence; the specific ARBA rule predicates were not available for inspection. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00026962 UNRESOLVED Rule identifier traced from the source annotation; detailed predicates were not inspected. Direct human import evidence independently supports the location.
GO:0005759 mitochondrial matrix	IEA GO_REF:0000044	ACCEPT	Summary: The UniProt subcellular-location mapping places SBCAD in the mitochondrial matrix, consistent with its processed mitochondrial precursor and matrix enzymatic role. Reason: The specific compartment is supported by UniProt curation and the mitochondrial import/assembly experiments in PMID:11013134. Import itself establishes the organelle; the matrix assignment also relies on curated compartment knowledge. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0170 SUPPORTS TRANSFER The source vocabulary term maps the explicit mitochondrial-matrix statement in the cached human UniProt record, not an unspecified mitochondrial compartment. Supporting Evidence: file:human/ACADSB/ACADSB-uniprot.txt Mitochondrion matrix
GO:0006631 fatty acid metabolic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Human recombinant SBCAD can dehydrogenate butyryl-CoA and hexanoyl-CoA (PMID:7698750), supporting this broad fatty-acid process as a secondary biochemical capacity. Reason: Keep the process with limited physiological scope: isoleucine catabolism is the established principal role. The reported human butyryl-CoA and hexanoyl-CoA activities provide positive biochemical support. The accessible abstract does not establish their quantitative contribution to whole-cell fatty-acid oxidation. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00028669 UNRESOLVED The ARBA rule is identified, but its conditions were not inspected. Non-core retention rests on reported human straight-chain substrate chemistry, not on an independently verified rule or a demonstrated major fatty-acid oxidation role.
GO:0016627 oxidoreductase activity, acting on the CH-CH group of donors	IEA GO_REF:0000002	ACCEPT	Summary: Dehydrogenation of the acyl-CoA alpha,beta carbon pair is oxidoreductase chemistry acting on CH-CH donors, as demonstrated by human SBCAD substrate assays (PMID:7698750). Reason: The term is broad but correctly describes the core catalytic reaction. Neither breadth nor overlap with the specific child activity constitutes biological over-annotation. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR006091 SUPPORTS TRANSFER The matched middle domain of acyl-CoA oxidases/dehydrogenases supports the catalytic fold; human assays resolve actual activity. InterPro:IPR009075 SUPPORTS TRANSFER The C-terminal acyl-CoA dehydrogenase/oxidase domain supports the broad reaction class, not a particular chain length. InterPro:IPR009100 SUPPORTS TRANSFER The N/middle-domain superfamily match is compatible with this broad catalytic assignment; direct human enzymology supplies functional grounding. InterPro:IPR013786 SUPPORTS TRANSFER The N-terminal acyl-CoA dehydrogenase/oxidase domain participates in the flavoprotein fold underlying this reaction class. InterPro:IPR036250 SUPPORTS TRANSFER The acyl-CoA dehydrogenase-like C-terminal superfamily match agrees with the experimentally active human enzyme. InterPro:IPR037069 SUPPORTS TRANSFER The N-terminal domain superfamily match supports the fold; it is not used alone to infer substrate preference. InterPro:IPR046373 SUPPORTS TRANSFER The middle-domain superfamily match is consistent with CH-CH oxidoreductase chemistry confirmed independently in human SBCAD.
GO:0016937 short-chain fatty acyl-CoA dehydrogenase activity	IEA GO_REF:0000120	ACCEPT	Summary: Short-chain fatty acyl-CoA dehydrogenase activity includes branched substrates; GO:0016937 does not restrict the substrate to a straight chain. The core 2-methylbutyryl reaction and reported butyryl activity fall within its short-chain scope. Reason: Accept the broader activity as encompassing core chemistry. The term specifies an aliphatic tail shorter than six carbons; hexanoyl-CoA is instead relevant to the separate medium-chain annotation. The human substrate activities are explicitly reported in the cached abstract of PMID:7698750. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00044591 UNRESOLVED Rule identifier is traced but detailed predicates were not inspected; other mapped sources and human substrate evidence independently support this term. RHEA:24004 SUPPORTS TRANSFER The cached human catalytic record maps butanoyl-CoA dehydrogenation, independently supported by the positive human recombinant-enzyme substrate report in PMID:7698750. RHEA:47196 SUPPORTS TRANSFER The source record describes short-chain acyl-CoA dehydrogenation; this broad category includes the branched core substrate. EC:1.3.8.1 SUPPORTS TRANSFER The curated short-chain acyl-CoA dehydrogenase EC assignment is compatible with the human substrate range, without requiring a distinct straight-chain physiological role.
GO:0046395 carboxylic acid catabolic process	IEA GO_REF:0000117	ACCEPT	Summary: ACADSB directly catalyzes a step in L-isoleucine breakdown (PMID:11013134), consistent with this broader carboxylic-acid catabolic process. Reason: The broad process encompasses the established core amino-acid catabolic role. Its generality is not a reason to classify the biology as non-core; no extra pathway is inferred. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00027882 UNRESOLVED The rule conditions were not independently inspected. The annotation is retained on the established human isoleucine-catabolic reaction, not on an assumed ARBA mechanism.
GO:0050660 flavin adenine dinucleotide binding	IEA GO_REF:0000002	ACCEPT	Summary: SBCAD binds FAD as the cofactor for acyl-CoA dehydrogenation. Human structure 2JIF contains FAD in the homotetramer, consistent with the UniProt cofactor record. Reason: FAD binding is an integral part of the catalytic mechanism, supported by structural and biochemical evidence. It is retained as an annotation but consolidated into the same enzyme core function. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR013786 SUPPORTS TRANSFER The N-terminal acyl-CoA dehydrogenase/oxidase domain match is consistent with the FAD-containing human enzyme and its structural cofactor. InterPro:IPR037069 SUPPORTS TRANSFER The corresponding N-terminal domain superfamily match supports cofactor-binding architecture; human FAD-containing structure 2JIF corroborates the assignment. Supporting Evidence: file:human/ACADSB/ACADSB-uniprot.txt Name=FAD file:human/ACADSB/ACADSB-uniprot.txt DR PDB; 2JIF; X-ray; 2.00 A; A/B/C/D=52-432.
GO:0070991 medium-chain fatty acyl-CoA dehydrogenase activity	IEA GO_REF:0000116	KEEP AS NON CORE	Summary: RHEA:43464 describes measured human hexanoyl-CoA dehydrogenation. C6 is inside the GO:0070991 medium-chain range of 6-12 carbons, so this activity is not excluded by the enzyme name or its dominant isoleucine role. Reason: The positive hexanoyl substrate result (PMID:7698750; curated UniProt reaction) supports the molecular activity. Retain it as a secondary substrate capacity; it does not establish a major physiological medium-chain fatty-acid oxidation role or activity on every C6-C12 substrate. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: RHEA:43464 SUPPORTS TRANSFER The cached human catalytic record explicitly lists hexanoyl-CoA to hexenoyl-CoA with ETF. The six-carbon substrate is within the live GO medium-chain definition; the secondary activity does not establish pathway dominance.
GO:0006550 L-isoleucine catabolic process	IEA GO_REF:0000041	ACCEPT	Summary: ACADSB catalyzes the 2-methylbutyryl-CoA to tiglyl-CoA step in L-isoleucine catabolism, consistent with the UniPathway mapping and human loss-of-function evidence (PMID:11013134). Reason: The enzyme performs the dehydrogenation step itself. Patient enzymology and recombinant activity establish participation, rather than a merely indirect requirement for this process. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniPathway:UPA00364 SUPPORTS TRANSFER The traced isoleucine-degradation pathway agrees with the catalytic pathway statement in human UniProt and the substrate-specific human defect.
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: The existing immunofluorescence-curation annotation places ACADSB in mitochondria, consistent with its independently established import and matrix function. Reason: Retain the experimental curator assignment with independent support from PMID:11013134. Individual source images were not re-evaluated here; the accepted organelle location is core and does not establish matrix localization by immunofluorescence alone.
GO:0003853 short-chain 2-methyl fatty acyl-CoA dehydrogenase activity	EXP PMID:10832746 2-Methylbutyryl-coenzyme A dehydrogenase deficiency: a new i...	ACCEPT	Summary: Patient fibroblast oxidation studies identified an isolated 2-methylbutyryl-CoA dehydrogenase block, and a recombinant variant abolished activity (PMID:10832746). Reason: The accessible abstract directly supports the human substrate-specific defect and enzyme activity. These data identify the core molecular function; no inaccessible full-text assay details are required for that conclusion. Supporting Evidence: PMID:10832746 an isolated block in 2-methylbutyryl-CoA dehydrogenase (2-MBCDase)
GO:0003853 short-chain 2-methyl fatty acyl-CoA dehydrogenase activity	EXP PMID:21430231 Role of isovaleryl-CoA dehydrogenase and short branched-chai...	ACCEPT	Summary: Purified human SBCAD activity was measured with 2-methylbutyryl-CoA while testing valproyl-CoA inhibition (PMID:21430231, figure 3 and cached text). Reason: The study directly assays the core substrate reaction. Its additional valproyl-CoA turnover and inhibition findings describe substrate breadth and drug-metabolite interactions; they do not define a separate core function or establish clinical toxicity causation. Supporting Evidence: PMID:21430231 The enzymatic activities of the three purified human enzymes were measured using optimized high-performance liquid chromatography procedures file:human/ACADSB/ACADSB-uniprot.txt one of the steps of the L-isoleucine catabolic
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: The MitoCoP-derived HTP annotation agrees with the established mitochondrial localization of ACADSB (PMID:34800366; PMID:11013134). Reason: Retain the curated mitochondrial assignment with independent import evidence. The full main proteomics article was read, but the ACADSB-specific supplementary measurements were not independently extracted; do not infer submitochondrial matrix resolution from this HTP row.
GO:0003853 short-chain 2-methyl fatty acyl-CoA dehydrogenase activity	IDA PMID:11013134 Isolated 2-methylbutyrylglycinuria caused by short/branched-...	ACCEPT	Summary: Patient fibroblast assays and expression of wild-type versus mutant human SBCAD support 2-methylbutyryl-CoA dehydrogenase activity (PMID:11013134). Reason: The original source directly reports the substrate-specific defect; its accessible methods and figure 3 further identify the COS-7 expression assay. This supports the core activity without requiring that all tested short-chain substrates behave identically. Supporting Evidence: PMID:11013134 using 2-methylbutyryl-CoA as substrate, confirmed the defect
GO:0005739 mitochondrion	IDA PMID:11013134 Isolated 2-methylbutyrylglycinuria caused by short/branched-...	ACCEPT	Summary: In vitro translated human SBCAD precursor was imported into isolated rat mitochondria and processed to a mature form (PMID:11013134, figure 4). Reason: The experiment directly supports mitochondrial targeting of the human protein in a heterologous organelle assay. This is the location of its core function; it is not a human-cell confocal localization experiment. Supporting Evidence: PMID:11013134 both wild-type proteins are imported into mitochondria
GO:0006550 L-isoleucine catabolic process	IMP PMID:11013134 Isolated 2-methylbutyrylglycinuria caused by short/branched-...	ACCEPT	Summary: The homozygous exon-10-skipping SBCAD variant and substrate-specific fibroblast defect demonstrate impaired human isoleucine breakdown (PMID:11013134). Reason: Genetic perturbation is supported by direct enzyme assays identifying the step ACADSB catalyzes. The enzyme is therefore a participant in the core catabolic process, not simply an indirect requirement. Supporting Evidence: PMID:11013134 it results in an isolated defect in isoleucine catabolism
GO:0042802 identical protein binding	IDA PMID:11013134 Isolated 2-methylbutyrylglycinuria caused by short/branched-...	KEEP AS NON CORE	Summary: Wild-type human SBCAD forms tetramers after mitochondrial import (PMID:11013134, native PAGE in figure 4); the human 2JIF biological assembly is also a homotetramer. Reason: Retain the observed self-association as a non-core binding annotation. This is positive oligomerization evidence, not an unspecified partner interaction; the catalytic core already describes the active enzyme without treating self-binding as a separate mechanism. Supporting Evidence: PMID:11013134 both wild-type proteins are imported into mitochondria and form tetramers file:human/ACADSB/ACADSB-uniprot.txt Homotetramer. file:human/ACADSB/ACADSB-uniprot.txt DR PDB; 2JIF; X-ray; 2.00 A; A/B/C/D=52-432.
GO:0003853 short-chain 2-methyl fatty acyl-CoA dehydrogenase activity	IDA PMID:7698750 Isolation and expression of a cDNA encoding the precursor fo...	ACCEPT	Summary: Recombinant human ACADSB dehydrogenates (S)-2-methylbutyryl-CoA, directly supporting its specific branched-chain activity (PMID:7698750). Reason: The accessible abstract explicitly reports the assayed human recombinant enzyme and substrates. The principal isoleucine-catabolic role is independently established by human patient studies. Supporting Evidence: PMID:7698750 activity toward the short branched chain acyl-CoA derivatives ((S)-2-methylbutyryl-CoA, isobutyryl-CoA, and 2-methylhexanoyl-CoA)
GO:0006631 fatty acid metabolic process	IDA PMID:7698750 Isolation and expression of a cDNA encoding the precursor fo...	KEEP AS NON CORE	Summary: The original human recombinant-enzyme study reports butyryl-CoA and hexanoyl-CoA turnover (PMID:7698750), supporting a secondary fatty-acid metabolic capacity. Reason: Retain the curator assignment with the scope of its positive biochemical substrate evidence. Isoleucine catabolism is the principal physiological role, while the accessible abstract does not establish the quantitative contribution of these additional substrate activities to whole-cell fatty-acid oxidation. Supporting Evidence: PMID:7698750 toward the short straight chain acyl-CoAs (butyryl-CoA and hexanoyl-CoA)
GO:0016937 short-chain fatty acyl-CoA dehydrogenase activity	IDA PMID:7698750 Isolation and expression of a cDNA encoding the precursor fo...	ACCEPT	Summary: The human substrate assay supports short-chain dehydrogenase activity through (S)-2-methylbutyryl-CoA and reported butyryl-CoA turnover (PMID:7698750). Reason: GO:0016937 includes branched substrates and encompasses the established core reaction. Hexanoyl-CoA is outside its less-than-six-carbon range and supports the separate medium-chain term. The reported human substrate activity positively supports retaining this experimental annotation. Supporting Evidence: PMID:7698750 toward the short straight chain acyl-CoAs (butyryl-CoA and hexanoyl-CoA)
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-70800	ACCEPT	Summary: Reactome R-HSA-70800 places the ACADSB-catalyzed 2-methylbutyryl-CoA to tiglyl-CoA reaction in the mitochondrial matrix. Reason: Accept the curated specific compartment, consistent with UniProt and mitochondrial import/assembly evidence. The structure-related N-terminal construct truncation in the event summary is not used to infer the physiological cleavage position.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838081	ACCEPT	Summary: The Reactome LONP1 degradation event supplies a mitochondrial-matrix location annotation, consistent with the independently established ACADSB compartment. Reason: Accept matrix localization with curator deference and independent support. The cached broad-event summary does not name ACADSB; this row is not treated as direct evidence that LONP1 degradation of ACADSB was individually assayed.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838093	ACCEPT	Summary: The Reactome LONP1 binding event supplies a mitochondrial-matrix annotation, matching the enzyme compartment recorded in human UniProt. Reason: The location is well supported independently. The cached summary describes a set of matrix substrates without naming ACADSB, so it does not independently establish a specific ACADSB-LONP1 binding assay or a new proteolytic function.
GO:0005739 mitochondrion	TAS PMID:7698750 Isolation and expression of a cDNA encoding the precursor fo...	ACCEPT	Summary: The original precursor-cloning study is the source of this mitochondrial-location assertion (PMID:7698750), consistent with subsequent direct import experiments. Reason: Retain the author-statement annotation with independent confirmation in PMID:11013134. The 1994 abstract identifies a precursor and mature protein but is not used to invent a particular localization assay. The organelle is the site of the core function.

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Notes

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