HADHB encodes the beta subunit of the mitochondrial trifunctional protein (MTP/TFP), a heterotetrameric complex (alpha2-beta2) that catalyzes the last three steps of long-chain fatty acid beta-oxidation. The beta subunit specifically possesses ONLY 3-ketoacyl-CoA thiolase activity (EC 2.3.1.155, 2.3.1.16), while the alpha subunit (HADHA) carries the enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase activities. The complex is located in the mitochondrial inner membrane, where it processes long-chain fatty acyl-CoA substrates (C10-C16). Mutations in HADHB cause mitochondrial trifunctional protein deficiency type 2 (MTPD2), an autosomal recessive disorder characterized by cardiomyopathy, myopathy, and peripheral neuropathy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003985 acetyl-CoA C-acetyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: This IBA annotation correctly assigns acetyl-CoA C-acetyltransferase activity to HADHB. The beta subunit possesses 3-ketoacyl-CoA thiolase activity, which includes this acetyltransferase function. PMID:8135828 demonstrated that "Expression of this cDNA [beta-subunit] in mammalian cells yielded a polypeptide with the long-chain 3-ketoacyl-CoA thiolase activity." Reason: Core molecular function of HADHB. The thiolase activity of the beta subunit is well established through direct expression studies (PMID:8135828) and confirmed by structural studies showing the thiolase active site in the beta subunit (PMID:30850536). Supporting Evidence: PMID:8135828 Expression of this cDNA in mammalian cells yielded a polypeptide with the long-chain 3-ketoacyl-CoA thiolase activity. |
| GO:0003985 acetyl-CoA C-acetyltransferase activity | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation based on Ensembl ortholog transfer. Consistent with the IBA annotation and experimental evidence showing HADHB has thiolase activity. Reason: Redundant with IBA but correctly captures the core thiolase function. Electronic annotation is consistent with experimental evidence. |
| GO:0003988 acetyl-CoA C-acyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: This IEA annotation correctly assigns acetyl-CoA C-acyltransferase activity to HADHB. This is essentially synonymous with 3-ketoacyl-CoA thiolase activity (EC 2.3.1.16). UniProt lists EC:2.3.1.16 for HADHB with evidence from multiple publications. Reason: Core molecular function. The acyltransferase activity is the same as the thiolase activity that characterizes the beta subunit. UniProt EC annotation (EC:2.3.1.16) is supported by PMID:7958339, PMID:8135828, PMID:8163672, and PMID:8651282. |
| GO:0003988 acetyl-CoA C-acyltransferase activity | TAS PMID:8135828 Structural analysis of cDNAs for subunits of human mitochond... | ACCEPT | Summary: This TAS annotation is correctly based on PMID:8135828, which directly demonstrated that expression of the beta-subunit cDNA yielded thiolase activity. This is a key paper that definitively assigned the thiolase activity to the beta subunit specifically. Reason: Core molecular function with strong direct evidence. PMID:8135828 showed "Expression of this cDNA [beta-subunit] in mammalian cells yielded a polypeptide with the long-chain 3-ketoacyl-CoA thiolase activity" while the alpha-subunit expression yielded hydratase and dehydrogenase activities. Supporting Evidence: PMID:8135828 Expression of this cDNA in mammalian cells yielded a polypeptide with the long-chain 3-ketoacyl-CoA thiolase activity. |
| GO:0050633 acetyl-CoA C-myristoyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: This IEA annotation assigns a specific long-chain thiolase activity (EC 2.3.1.155) to HADHB. UniProt lists this EC number for HADHB. The MTP complex shows specificity for long-chain fatty acids (C10-C16), and myristoyl-CoA (C14) is within this range. Reason: Appropriate specific thiolase activity. HADHB is annotated with EC:2.3.1.155 in UniProt based on PMID:7958339, PMID:8135828, PMID:8163672, and PMID:8651282. This reflects the long-chain substrate specificity of the enzyme. |
| GO:0003857 (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity | TAS PMID:1550553 Human liver long-chain 3-hydroxyacyl-coenzyme A dehydrogenas... | REMOVE | Summary: CRITICAL ERROR: This annotation incorrectly assigns 3-hydroxyacyl-CoA dehydrogenase activity to HADHB. PMID:1550553 (1992) characterized the whole trifunctional enzyme complex before the subunit-specific activities were determined. The subsequent study PMID:8135828 (1994) definitively showed that the ALPHA subunit (HADHA), not the beta subunit (HADHB), carries the dehydrogenase activity. Reason: This activity belongs to HADHA, not HADHB. PMID:8135828 clearly demonstrated: "Expression of this cDNA [alpha-subunit] in mammalian cells yielded a polypeptide with the long-chain enoyl-CoA hydratase and long-chain 3-hydroxyacyl-CoA dehydrogenase activities." The beta subunit expression only yielded thiolase activity. UniProt correctly notes that "the trifunctional enzyme subunit alpha/HADHA carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities." Supporting Evidence: PMID:8135828 Expression of this cDNA in mammalian cells yielded a polypeptide with the long-chain enoyl-CoA hydratase and long-chain 3-hydroxyacyl-CoA dehydrogenase activities |
| GO:0004300 enoyl-CoA hydratase activity | TAS PMID:1550553 Human liver long-chain 3-hydroxyacyl-coenzyme A dehydrogenas... | REMOVE | Summary: CRITICAL ERROR: This annotation incorrectly assigns enoyl-CoA hydratase activity to HADHB. PMID:1550553 (1992) characterized the whole trifunctional enzyme complex before the subunit-specific activities were determined. The subsequent study PMID:8135828 (1994) definitively showed that the ALPHA subunit (HADHA), not the beta subunit (HADHB), carries the hydratase activity. Reason: This activity belongs to HADHA, not HADHB. PMID:8135828 clearly demonstrated: "Expression of this cDNA [alpha-subunit] in mammalian cells yielded a polypeptide with the long-chain enoyl-CoA hydratase and long-chain 3-hydroxyacyl-CoA dehydrogenase activities." The beta subunit expression only yielded thiolase activity. The crystal structure (PMID:30850536) confirms that ECH (hydratase) and HAD (dehydrogenase) active sites are in the alpha subunits. Supporting Evidence: PMID:8135828 Expression of this cDNA in mammalian cells yielded a polypeptide with the long-chain enoyl-CoA hydratase and long-chain 3-hydroxyacyl-CoA dehydrogenase activities PMID:30850536 The biological unit of the protein is alpha2beta2... employing 2-enoyl-CoA hydratase (ECH), 3-hydroxyl-CoA dehydrogenase (HAD), and 3-ketothiolase (KT) activities consecutively. [ECH and HAD are in alpha subunit, KT in beta] |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Very broad term based on UniProt keyword mapping. HADHB does have transferase activity (thiolase is a type of transferase), but this is too general to be informative. Reason: Technically correct but uninformative. The more specific thiolase/acyltransferase terms (GO:0003985, GO:0003988) better capture the molecular function. |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Parent term of the more specific acetyl-CoA C-acyltransferase activity. Correct but less informative than the specific child terms. Reason: Technically correct parent term. The more specific terms (GO:0003988, GO:0003985) should be used as core function annotations. |
| GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro-based annotation capturing the thiolase domain function. Correct but less specific than the acetyl-CoA C-acyltransferase terms. Reason: Correct parent term based on thiolase domain (InterPro:IPR002155). More specific child terms should be used for core function. |
| GO:0005515 protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | KEEP AS NON CORE | Summary: IPI annotation based on interaction with GABARAPL1. The interaction was detected in a network study of the autophagy system. Reason: Generic protein binding term. Does not inform about specific molecular function. However, the interaction with autophagy machinery may be biologically relevant for mitochondrial quality control. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: IPI annotation based on interaction with HADHA (the alpha subunit). This reflects the obligate heterotetrameric complex formation between alpha and beta subunits. Reason: While this is technically correct (HADHB must bind HADHA to form the functional complex), "protein binding" is uninformative. The key interaction is captured by the complex membership annotation (GO:0016507). |
| GO:0005515 protein binding | IPI PMID:29915090 Cryo-EM structure of human mitochondrial trifunctional prote... | KEEP AS NON CORE | Summary: IPI annotation from cryo-EM structure study showing HADHB-HADHA interaction in the TFP complex. Reason: Reflects obligate complex formation. Complex membership (GO:0016507) is more informative than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:30850536 Crystal structure of human mitochondrial trifunctional prote... | KEEP AS NON CORE | Summary: IPI annotation from crystal structure study showing HADHB-HADHA interaction. Reason: Same as above - reflects obligate complex formation captured better by GO:0016507. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: IPI annotation from interactome study showing HADHB-HADHA interaction. Reason: Redundant generic protein binding annotation. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: IPI annotation from multimodal cell maps study showing HADHB-HADHA interaction. Reason: Redundant generic protein binding annotation. |
| GO:0005515 protein binding | IPI PMID:32243843 Mitoregulin Controls Ξ²-Oxidation in Human and Mouse Adipocyt... | KEEP AS NON CORE | Summary: IPI annotation based on interaction with MTLN (mitoregulin). The study showed that the TFP complex interacts with MTLN to regulate beta-oxidation. Reason: Interesting regulatory interaction but generic term is uninformative. The biological significance is in the regulation of beta-oxidation. |
| GO:0005515 protein binding | IPI PMID:21527675 Human cytomegalovirus directly induces the antiviral protein... | KEEP AS NON CORE | Summary: IPI annotations based on interaction with RSAD2/viperin. HCMV-induced viperin relocalizes to mitochondria and interacts with TFP to reduce ATP generation. Reason: This interaction represents viral subversion of host metabolism. Viperin interaction with TFP "reduced cellular ATP generation, which resulted in actin cytoskeleton disruption." Interesting but not a core function. Supporting Evidence: PMID:21527675 viperin interacted with the mitochondrial trifunctional protein that mediates beta-oxidation of fatty acids to generate adenosine triphosphate (ATP). This interaction with viperin... reduced cellular ATP generation |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | KEEP AS NON CORE | Summary: HDA annotation from large-scale mRNA interactome capture study. HADHB was identified among 860 proteins that qualify as RNA-binding proteins in HeLa cells. The study noted that many metabolic enzymes unexpectedly bind RNA. Reason: Possible moonlighting function. The interactome capture study identified many metabolic enzymes as RNA-binding proteins. This may represent a regulatory mechanism linking metabolism to RNA fate, but it is not the core function of HADHB. Supporting Evidence: PMID:22658674 shedding light on RBPs in disease, RNA-binding enzymes of intermediary metabolism |
| GO:0106222 lncRNA binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA annotation transferred from mouse ortholog. Related to the general RNA binding observed in interactome studies. Reason: Possible moonlighting function transferred from ortholog. Not a core function. |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA annotation transferred from rat ortholog. Very generic term. Reason: Too generic to be informative. The complex membership (GO:0016507) better captures the relevant biology. |
| GO:0006635 fatty acid beta-oxidation | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation correctly placing HADHB in the fatty acid beta-oxidation pathway. The TFP complex catalyzes the last three steps of mitochondrial long-chain fatty acid beta-oxidation. Reason: Core biological process. HADHB is an essential subunit of the TFP complex that performs beta-oxidation. Multiple structural and functional studies confirm this (PMID:29915090, PMID:30850536, PMID:8135828). Supporting Evidence: PMID:29915090 The mitochondrial trifunctional protein (TFP) catalyzes three reactions in the fatty acid beta-oxidation process. PMID:8135828 Trifunctional protein deficiency, a typical mitochondrial long-chain fatty acid beta-oxidation defect |
| GO:0006635 fatty acid beta-oxidation | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation consistent with the IBA and experimental evidence. Reason: Redundant with IBA but correctly captures core biological process. |
| GO:0006635 fatty acid beta-oxidation | IDA PMID:29915090 Cryo-EM structure of human mitochondrial trifunctional prote... | ACCEPT | Summary: IDA annotation from the cryo-EM structure study. The study directly demonstrated TFP function in beta-oxidation through structural analysis. Reason: Core biological process with direct structural evidence. The cryo-EM structure revealed the architecture of the functional beta-oxidation complex. Supporting Evidence: PMID:29915090 The mitochondrial trifunctional protein (TFP) catalyzes three reactions in the fatty acid beta-oxidation process. |
| GO:0006635 fatty acid beta-oxidation | TAS PMID:1550553 Human liver long-chain 3-hydroxyacyl-coenzyme A dehydrogenas... | ACCEPT | Summary: TAS annotation from early characterization of the trifunctional enzyme. While PMID:1550553 did not distinguish subunit-specific activities, the assignment of beta-oxidation to the whole complex (including HADHB) is correct. Reason: Core biological process. The TFP complex including HADHB participates in beta-oxidation, even though this paper preceded the subunit-specific activity assignments. |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Very broad parent term of fatty acid beta-oxidation. Based on UniProt keyword mapping. Reason: Correct but too general. The more specific term GO:0006635 (fatty acid beta-oxidation) should be used for core function. |
| GO:0006631 fatty acid metabolic process | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Parent term of fatty acid beta-oxidation. Based on UniProt keyword mapping. Reason: Correct but less specific than GO:0006635. |
| GO:0010467 gene expression | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA annotation transferred from mouse ortholog. Unexpected term for a metabolic enzyme. May relate to RNA binding observations or indirect effects. Reason: This is likely an over-annotation. There is no clear mechanistic link between HADHB's thiolase activity and gene expression regulation. May be an artifact of the RNA binding observations or indirect metabolic effects. |
| GO:0071222 cellular response to lipopolysaccharide | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA annotation transferred from mouse ortholog. This may reflect changes in fatty acid metabolism during immune responses, but is unlikely to be a core function of HADHB. Reason: Likely over-annotation. HADHB's primary function is in fatty acid beta-oxidation, not immune signaling. Any involvement in LPS response would be indirect through metabolic changes. |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation based on UniProt subcellular location. Correct localization supported by extensive experimental evidence. Reason: Core cellular localization. The TFP complex is membrane-bound and associates with the mitochondrial inner membrane (PMID:29915090, PMID:30850536). |
| GO:0005743 mitochondrial inner membrane | IDA PMID:29915090 Cryo-EM structure of human mitochondrial trifunctional prote... | ACCEPT | Summary: IDA annotation from cryo-EM structure study. The structure revealed how the TFP complex associates with the mitochondrial inner membrane. Reason: Core cellular localization with strong structural evidence. The cryo-EM study showed "A concave surface of the TFP tetramer interacts with the detergent molecules in the structure, suggesting that this region is involved in associating with the membrane." Supporting Evidence: PMID:29915090 A concave surface of the TFP tetramer interacts with the detergent molecules in the structure, suggesting that this region is involved in associating with the membrane. |
| GO:0005743 mitochondrial inner membrane | IDA PMID:21527675 Human cytomegalovirus directly induces the antiviral protein... | ACCEPT | Summary: IDA annotation from viperin interaction study. Subcellular fractionation confirmed HADHB localization. Reason: Core cellular localization confirmed by multiple studies. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-1482775 | ACCEPT | Summary: TAS annotation from Reactome pathway curation. Reason: Correct localization from pathway database curation. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-77271 | ACCEPT | Summary: TAS annotation from Reactome pathway for beta-oxidation of tetradecanoyl-CoA. Reason: Correct localization for beta-oxidation reactions. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-77277 | ACCEPT | Summary: TAS annotation from Reactome. Note this Reactome entry (hydratase reaction) would be more appropriate for HADHA, but the localization itself is correct for both subunits since they form an obligate complex. Reason: Localization is correct even if the reaction annotation would be more appropriate for HADHA. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-77283 | ACCEPT | Summary: TAS annotation from Reactome. Note this Reactome entry (dehydrogenase reaction) would be more appropriate for HADHA, but the localization is correct. Reason: Localization is correct for both subunits. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-77301 | ACCEPT | Summary: TAS annotation from Reactome pathway. Reason: Correct localization. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-77303 | ACCEPT | Summary: TAS annotation from Reactome pathway. Reason: Correct localization. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-77304 | ACCEPT | Summary: TAS annotation from Reactome pathway (thiolase reaction). This correctly reflects HADHB's thiolase activity at the inner membrane. Reason: Correct localization for thiolase reaction. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-77309 | ACCEPT | Summary: TAS annotation from Reactome pathway. Reason: Correct localization. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-77321 | ACCEPT | Summary: TAS annotation from Reactome pathway. Reason: Correct localization. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-77329 | ACCEPT | Summary: TAS annotation from Reactome pathway. Reason: Correct localization. |
| GO:0005743 mitochondrial inner membrane | TAS Reactome:R-HSA-77340 | ACCEPT | Summary: TAS annotation from Reactome pathway. Reason: Correct localization. |
| GO:0016507 mitochondrial fatty acid beta-oxidation multienzyme complex | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation correctly placing HADHB as part of the mitochondrial TFP complex. HADHB is the beta subunit of the alpha2-beta2 heterotetrameric complex. Reason: Core cellular component. HADHB is an obligate component of the TFP complex. The complex structure has been determined by cryo-EM (PMID:29915090) and X-ray crystallography (PMID:30850536). Supporting Evidence: PMID:29915090 Here we report a 4.2-Γ
cryo-electron microscopy Ξ±2Ξ²2 tetrameric structure of the human TFP PMID:30850536 The biological unit of the protein is Ξ±2Ξ²2 |
| GO:0016507 mitochondrial fatty acid beta-oxidation multienzyme complex | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation consistent with IBA and experimental evidence. Reason: Redundant with IBA but correctly captures core complex membership. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: General mitochondrial localization. Correct but less specific than inner membrane annotation. Reason: Correct but more specific terms (GO:0005743, GO:0016507) better capture the localization. |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: IDA annotation from HPA immunofluorescence data. Reason: Correct but less specific than inner membrane annotation. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | KEEP AS NON CORE | Summary: HTP annotation from quantitative mitochondrial proteome study. Reason: Correct mitochondrial localization from proteomics. |
| GO:0005739 mitochondrion | NAS PMID:7958339 The mitochondrial long-chain trifunctional enzyme: 2-enoyl-C... | KEEP AS NON CORE | Summary: NAS annotation from early review paper on the trifunctional enzyme. Reason: Correct but less specific than inner membrane annotation. |
| GO:0005740 mitochondrial envelope | TAS PMID:1550553 Human liver long-chain 3-hydroxyacyl-coenzyme A dehydrogenas... | KEEP AS NON CORE | Summary: TAS annotation from early characterization. This is a parent term of mitochondrial inner membrane. The paper described the enzyme as "membrane-bound" but did not specify inner vs outer membrane. Reason: Correct but less specific than GO:0005743 (mitochondrial inner membrane). Subsequent studies confirmed inner membrane localization. |
| GO:0005741 mitochondrial outer membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA annotation based on UniProt subcellular location. UniProt lists both inner and outer membrane localization. Reason: The primary localization is the inner membrane where the complex is active. Outer membrane localization may reflect import intermediates or interactions with outer membrane proteins. |
| GO:0005741 mitochondrial outer membrane | IDA PMID:21527675 Human cytomegalovirus directly induces the antiviral protein... | KEEP AS NON CORE | Summary: IDA annotation from viperin interaction study. The study used subcellular fractionation and found HADHB in both inner and outer membrane fractions. Reason: May represent interaction with outer membrane during viral infection or import intermediates. The functional complex is at the inner membrane. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA annotation based on UniProt subcellular location. UniProt lists ER localization based on PMID:21527675. Reason: This likely represents ER localization during viral infection (HCMV-induced viperin causes relocalization) rather than normal function. The core localization is mitochondrial inner membrane. |
| GO:0005783 endoplasmic reticulum | IDA PMID:21527675 Human cytomegalovirus directly induces the antiviral protein... | KEEP AS NON CORE | Summary: IDA annotation from viperin study. HCMV infection causes viperin-mediated redistribution of cellular proteins including TFP components. Reason: This represents pathological/viral-induced localization, not the normal cellular localization. The paper showed viperin "relocalization from the endoplasmic reticulum to the mitochondria" during infection. Supporting Evidence: PMID:21527675 Viperin interaction with the viral protein vMIA resulted in viperin relocalization from the endoplasmic reticulum to the mitochondria. |
| GO:0042645 mitochondrial nucleoid | IDA PMID:18063578 The layered structure of human mitochondrial DNA nucleoids. | KEEP AS NON CORE | Summary: IDA annotation from nucleoid proteomics study. HADHB was identified in native nucleoid preparations but was not found to cross-link to mtDNA, suggesting it is in the peripheral region of nucleoids. Reason: The study found HADHB in native nucleoids but noted that "Several other metabolic proteins and chaperones identified in native nucleoids... were not observed to cross-link to mtDNA." This suggests HADHB is in the peripheral region where "translation and complex assembly may occur" rather than being a core nucleoid component. Supporting Evidence: PMID:18063578 Several other metabolic proteins and chaperones identified in native nucleoids... were not observed to cross-link to mtDNA... translation and complex assembly may occur in the peripheral region. |
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Download this section (compressed HTML)Q: Should the Reactome annotations for hydratase and dehydrogenase reactions be removed from HADHB and retained only for HADHA? Currently both subunits are annotated to all reactions in the beta-oxidation pathway.
Q: What is the functional significance of HADHB's RNA binding activity detected in interactome capture studies (PMID:22658674)?
Experiment: Confirm that isolated recombinant HADHB (beta subunit alone) lacks hydratase and dehydrogenase activities to definitively rule out any residual activity.
Hypothesis: Recombinant HADHB expressed alone will have no detectable enoyl-CoA hydratase or 3-hydroxyacyl-CoA dehydrogenase activity, confirming these are HADHA-specific.
Experiment: Investigate whether the RNA binding by HADHB detected in PMID:22658674 has any regulatory significance for fatty acid metabolism.
Hypothesis: RNA binding by HADHB may represent a moonlighting function that links metabolic state to post-transcriptional regulation of lipid metabolism genes.
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