AGL (glycogen debranching enzyme, GDE) is a large bifunctional enzyme that removes glycogen branch points during cytosolic glycogenolysis. Its GH13 transferase region transfers a short alpha-1,4-linked glucan segment to another chain, leaving one glucose attached at the branch point. Its GH133 glucosidase region then hydrolyses that alpha-1,6 linkage to release free glucose, allowing glycogen phosphorylase to continue degradation. Glycogen binding helps position and stabilize the enzyme. The two catalytic activities reside in the same polypeptide; purified human AGL can form both monomers and dimers. AGL is also detected in nuclear compartments, whose physiological contribution is less well defined. Biallelic loss of AGL function causes glycogen storage disease type III (Cori or Forbes disease), with accumulation of glycogen bearing short outer chains and variable liver, skeletal-muscle and cardiac involvement.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004135 amylo-alpha-1,6-glucosidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: AGL hydrolyses exposed alpha-1,6 branch linkages in phosphorylase limit dextrin. Reason: The PAINT ancestral assertion at PTN000060165 agrees with the human glucosidase reaction and direct human enzymatic characterization in PMID:40593796. This is one of the two conserved catalytic functions of AGL. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000060165 SUPPORTS TRANSFER The cached PTHR10569 PAINT table records this IBD node for the corresponding term. Human AGL retains the activity or process; human experimental descendants among the catalytic evidence are legitimate grounding of the ancestral assertion, not circularity. Supporting Evidence: file:human/AGL/AGL-uniprot.txt Hydrolysis of (1->6)-alpha-D-glucosidic branch linkages in...glycogen phosphorylase limit dextrin. |
| GO:0005980 glycogen catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: AGL directly catalyses glycogen debranching during glycogen breakdown. Reason: PTN000060165 places glycogen catabolism in the inherited function of this enzyme family. Human AGL performs both the chain-transfer and branch-hydrolysis steps; the human Reactome reactions and five cached mouse Agl GO-CAM models place these activities in glycogen catabolism. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000060165 SUPPORTS TRANSFER The cached PTHR10569 PAINT table records this IBD node for the corresponding term. Human AGL retains the activity or process; human experimental descendants among the catalytic evidence are legitimate grounding of the ancestral assertion, not circularity. Supporting Evidence: file:human/AGL/AGL-uniprot.txt in glycogen degradation. |
| GO:0004134 4-alpha-glucanotransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: AGL transfers an alpha-1,4-linked glucan segment away from a glycogen branch. Reason: The PTN000060165 assertion is supported by the conserved human transferase reaction and recombinant-human enzymatic assays in PMID:40593796. The transferase and glucosidase activities occupy distinct regions of the same protein. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000060165 SUPPORTS TRANSFER The cached PTHR10569 PAINT table records this IBD node for the corresponding term. Human AGL retains the activity or process; human experimental descendants among the catalytic evidence are legitimate grounding of the ancestral assertion, not circularity. Supporting Evidence: file:human/AGL/AGL-uniprot.txt Transfers a segment of a (1->4)-alpha-D-glucan to a new...position in an acceptor, which may be glucose or a (1->4)-alpha-D-...glucan. |
| GO:0004134 4-alpha-glucanotransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined electronic methods recover the established AGL transferase activity. Reason: The EC and InterPro matches, together with mammalian ortholog evidence, agree with the human reaction. PMID:40593796 measures oligosaccharide transfer by purified human AGL rather than inferring catalysis from the family name alone. Supporting Evidence: file:human/AGL/AGL-uniprot.txt Transfers a segment of a (1->4)-alpha-D-glucan to a new...position in an acceptor, which may be glucose or a (1->4)-alpha-D-...glucan. |
| GO:0004135 amylo-alpha-1,6-glucosidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined electronic methods recover AGL alpha-1,6-glucosidase activity. Reason: The EC and debranching-enzyme family mappings are consistent with the branch-linkage hydrolysis reaction of human AGL and the independent glucosidase assay in PMID:40593796. Supporting Evidence: file:human/AGL/AGL-uniprot.txt Hydrolysis of (1->6)-alpha-D-glucosidic branch linkages in...glycogen phosphorylase limit dextrin. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: AGL has a cytoplasmic pool associated with glycogen metabolism. Reason: The broad cytoplasm annotation is supported by the UniProt record and independent human HPA cytosolic staining. Retain the source compartment resolution; the more specific cytosol annotations are separately present. Supporting Evidence: file:human/AGL/AGL-uniprot.txt Cytoplasm |
| GO:0005975 carbohydrate metabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: AGL catalyses two reactions in carbohydrate metabolism. Reason: InterPro:IPR008928 identifies the glycosidase superfamily. Carbohydrate metabolism is a correct broad process for the established glycogen-debranching chemistry; the specific glycogen-catabolism annotations provide complementary resolution. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR008928 SUPPORTS TRANSFER The six-hairpin glycosidase superfamily match is consistent with the known carbohydrate-processing activity of human AGL. Retain this broad electronic process assertion. Supporting Evidence: file:human/AGL/AGL-uniprot.txt in glycogen degradation. |
| GO:0005978 glycogen biosynthetic process | IEA GO_REF:0000002 | REMOVE | Summary: The InterPro glycogen-formation mapping misstates the established pathway role of AGL. Reason: GO:0005978 describes formation of glycogen. Human AGL instead transfers a short glucan segment to expose a branch-point glucose and hydrolyses that glucose, enabling phosphorylase-mediated glycogen breakdown. The IPR006421 metazoan debranching-family assignment is credible, but mapping that family to glycogen formation conflates its established degradative role with biosynthesis. The glycogen-repletion/branching model discussed in PMID:17908927 does not demonstrate a biosynthetic step performed by AGL. A possible additional role remains an expert question rather than support for this electronic assertion. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: InterPro:IPR006421 SOURCE BAD The family identification is retained. The associated glycogen-biosynthesis mapping assigns the wrong pathway role to the established metazoan glycogen-debranching chemistry; this judgment concerns the GO mapping, not the protein-family match or a plant-family misassignment. Supporting Evidence: file:human/AGL/AGL-uniprot.txt in glycogen degradation. |
| GO:0005980 glycogen catabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic glycogen-catabolism annotation matches AGL chemistry. Reason: InterPro:IPR010401 and mammalian ortholog evidence identify the same two-step debranching function documented for human AGL. The protein itself carries out the steps that allow further glycogen degradation. Supporting Evidence: file:human/AGL/AGL-uniprot.txt in glycogen degradation. |
| GO:0005634 nucleus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: AGL can occupy a nuclear compartment in addition to the cytosol. Reason: The mouse donor study PMID:17908927 used mouse-liver Agl cDNA and observed partial nuclear redistribution of tagged protein in HepG2 cells under glycogenolytic conditions. Independent human HPA data support nucleoplasm and nuclear bodies. Retain nuclear localization while leaving its physiological function unresolved. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: Ensembl:ENSMUSP00000044012 SUPPORTS TRANSFER Mouse Agl/F8VPN4 is the Compara source. Its primary experiment establishes conditional nuclear localization; independent human HPA staining supports the target compartment without assigning the same stimulus dependence to HPA cells. Supporting Evidence: PMID:17908927 approximately 90% of transfected cells exhibit partial nuclear staining for AGL |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: The ortholog-transferred cytosol annotation agrees with human AGL localization. Reason: The source is mouse Agl, and direct human HPA cytosol staining and both human Reactome catalytic events independently establish this core compartment. The conclusion does not require the mouse experiment to have tested human protein. Propagation Review Root cause: NO FAILURE CORE Sources checked: Ensembl:ENSMUSP00000044012 SUPPORTS TRANSFER Mouse Agl cytosolic localization is conserved in the human target, independently supported by HPA and the human catalytic reactions. |
| GO:0007584 response to nutrient | IEA GO_REF:0000107 | UNDECIDED | Summary: The rat-derived nutrient-response assertion requires its original experimental context. Reason: The donor trace points to rat Agl and PMID:1413626, whose accessible abstract describes biogenic-amine effects in isolated rat hepatocytes. The full study needed to assess the nutrient-response assignment was not recovered. Mouse liver starvation/refeeding results in PMID:17908927 corroborate regulation of Agl abundance but do not resolve this specific rat-source annotation or its human transfer. Propagation Review Root cause: UNRESOLVED Sources checked: Ensembl:ENSRNOP00000052593 UNRESOLVED Rat Agl/D4AEH9 is the source; the MGI ortholog evidence view identifies PMID:1413626. PubMed verifies the rat-hepatocyte study, but full-text access and transfer interpretation remain unresolved. |
| GO:0009725 response to hormone | IEA GO_REF:0000107 | UNDECIDED | Summary: A rat biogenic-amine study underlies the hormone-response transfer. Reason: PMID:1413626 reports modulation of debranching-enzyme activity in isolated rat hepatocytes. Its complete assays and the physiological basis of the hormone-response assignment remain inaccessible. Hormonal regulation of glycogen metabolism is relevant context, but it is insufficient to finish the source-specific human annotation review. Propagation Review Root cause: UNRESOLVED Sources checked: Ensembl:ENSRNOP00000052593 UNRESOLVED Rat Agl/D4AEH9 is the source; the MGI ortholog evidence view identifies PMID:1413626. PubMed verifies the rat-hepatocyte study, but full-text access and transfer interpretation remain unresolved. |
| GO:0016234 inclusion body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Wild-type Agl can enter inclusions during experimental proteasome impairment. Reason: The full Results and Figure 2 of PMID:17908927 compare wild-type mouse Agl with carbohydrate-binding mutants in transfected COS cells. MG132 produced aggregates in wild-type-expressing cells too, although less frequently than for the mutants. Retain the conserved stress-associated localization as non-core; it is not evidence for a constitutive catalytic compartment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: Ensembl:ENSMUSP00000044012 SUPPORTS TRANSFER The mouse donor primary study explicitly includes wild-type inclusion formation during proteasome inhibition. The restricted treatment and overexpression context is retained; the evidence is not mutant-only. |
| GO:0016529 sarcoplasmic reticulum | IEA GO_REF:0000107 | UNDECIDED | Summary: Rat skeletal-muscle Agl has positive evidence of sarcoplasmic-reticulum association. Reason: PMID:15180797 reports debranching-enzyme protein and activity in rat muscle SR vesicles, with glycogen depletion reducing the associated pool. This is positive biochemical localization evidence and does not require Agl to be an integral membrane protein. The full source was not recovered to audit its controls or the human transfer; cytosolic activity does not contradict peripheral SR association. Propagation Review Root cause: UNRESOLVED Sources checked: Ensembl:ENSRNOP00000052593 UNRESOLVED The rat donor is linked to an actual SR-fractionation experiment in PMID:15180797. The abstract supports association; full methods and the human conservation assessment remain unresolved. No contamination claim is made. |
| GO:0030246 carbohydrate binding | IEA GO_REF:0000107 | MODIFY | Summary: Human AGL binds glycogen, supporting a more specific carbohydrate-binding term. Reason: The rat donor is traced to PMID:6449198, whose local record contains no experimental text. Independently, PMID:40593796 measures purified human AGL binding to glycogen immobilized on ConA beads (Methods, Glycogen binding assay; Figure 2i). This positive human experiment supports GO:2001069, a descendant of carbohydrate binding, without claiming that the inaccessible rat experiment has been reverified. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: Ensembl:ENSRNOP00000052593 UNRESOLVED The original rat source PMID:6449198 remains title-only. The recommended specificity is grounded independently in the human glycogen-binding assay of PMID:40593796, not an invented donor assay. Proposed replacements: glycogen binding Supporting Evidence: PMID:40593796 The binding capability of glycogen and hsGDE was assayed via pull-down assay |
| GO:0030247 polysaccharide binding | IEA GO_REF:0000107 | MODIFY | Summary: The polysaccharide-binding annotation can be specified as glycogen binding. Reason: PMID:17908927 demonstrates carbohydrate binding by mouse Agl using amylose resin and glycogen-enriched fractions. PMID:40593796 supplies direct purified-human glycogen pull-down evidence. GO:2001069 specifies the physiological ligand and is a child of polysaccharide binding; this is a supported refinement of the existing assertion, not an additional redundant annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: Ensembl:ENSMUSP00000044012 SUPPORTS TRANSFER Mouse Agl binding experiments support the broad source term; independent human glycogen pull-down supports the proposed ligand-specific descendant. Proposed replacements: glycogen binding Supporting Evidence: PMID:40593796 The binding capability of glycogen and hsGDE was assayed via pull-down assay |
| GO:0031593 polyubiquitin modification-dependent protein binding | IEA GO_REF:0000107 | REMOVE | Summary: The donor experiment measures covalent ubiquitination of Agl. Reason: GO:0031593 means binding a target protein upon its polyubiquitination. In PMID:17908927 Figures 1F and 4, tagged Agl was immunoprecipitated after SDS denaturation and boiling, and anti-ubiquitin detected covalent modification of Agl itself. The full source therefore supports Agl as a ubiquitination substrate, rather than the molecular recognition asserted by this propagated term. Propagation Review Root cause: SOURCE BAD Failure modes: ROLE CONFLATION Sources checked: Ensembl:ENSMUSP00000044012 SOURCE BAD MGI links the mouse source annotation to PMID:17908927. Its denaturing immunoprecipitation assay tests ubiquitination of Agl, not Agl binding to a protein conditional on that partner being polyubiquitinated. Supporting Evidence: |
| GO:0051384 response to glucocorticoid | IEA GO_REF:0000107 | UNDECIDED | Summary: The glucocorticoid-response transfer derives from fetal rat liver. Reason: PubMed-verified PMID:120213 reports effects of fetal pituitary/adrenal manipulations and cortisol on amylo-1,6-glucosidase activity, including repression by cortisol. The full French-language study was not recovered. The developmental, tissue and treatment boundaries must be assessed before treating this as an established human AGL response. Propagation Review Root cause: UNRESOLVED Sources checked: Ensembl:ENSRNOP00000052593 UNRESOLVED The traced donor experiment is fetal rat liver in PMID:120213. The accessible abstract supports hormone sensitivity, while full-source assessment and transfer to human remain unresolved. |
| GO:0005980 glycogen catabolic process | TAS Reactome:R-HSA-70221 | ACCEPT | Summary: Reactome places AGL in the glycogen-breakdown pathway. Reason: The live pathway and its two AGL catalytic events identify the transferase and glucosidase steps of glycogenolysis. AGL performs the chemistry rather than merely being required for the pathway outcome. Supporting Evidence: file:human/AGL/AGL-uniprot.txt in glycogen degradation. |
| GO:0004134 4-alpha-glucanotransferase activity | EXP PMID:2961257 Glycogen debranching enzyme: purification, antibody characte... | ACCEPT | Summary: The transferase EXP annotation agrees with direct human AGL biochemistry. Reason: PMID:2961257 purified porcine enzyme and tested immunochemical similarity and inhibition of human liver enzyme; its local text is abstract-only. Retain the established catalytic annotation with curator deference, reinforced by the separately measured human transferase activity in PMID:40593796. The porcine purification is not described as a purified-human assay. Supporting Evidence: file:human/AGL/AGL-uniprot.txt Transfers a segment of a (1->4)-alpha-D-glucan to a new...position in an acceptor, which may be glucose or a (1->4)-alpha-D-...glucan. |
| GO:0004135 amylo-alpha-1,6-glucosidase activity | EXP PMID:2961257 Glycogen debranching enzyme: purification, antibody characte... | ACCEPT | Summary: The glucosidase EXP annotation agrees with direct human AGL biochemistry. Reason: The original study PMID:2961257 connects porcine purified debranching enzyme with human liver activity and patient immunoblots. Its abstract does not resolve every catalytic assay detail, but human glucosidase activity is independently established by PMID:40593796. Retain this known core function without treating loss of an immunoblot band as proof of a particular reaction. Supporting Evidence: file:human/AGL/AGL-uniprot.txt Hydrolysis of (1->6)-alpha-D-glucosidic branch linkages in...glycogen phosphorylase limit dextrin. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Human HPA imaging supports nucleoplasmic AGL. Reason: The live HPA AGL subcellular page lists nucleoplasm as a supported main location. Retain this directly observed human compartment; the source does not establish a separate nuclear catalytic role. Glycogen-depletion-dependent redistribution in a different transfection study is not assigned to the HPA experiment. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Human HPA imaging supports a cytosolic AGL pool. Reason: The live HPA AGL page lists supported cytosolic localization. This is the compartment in which the two human glycogen-debranching reactions operate, consistent with the established enzyme mechanism. |
| GO:0016604 nuclear body | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Human HPA imaging supports AGL in nuclear bodies. Reason: HPA lists nuclear bodies as a supported additional location. This is retained at the observed anatomical resolution; neither a glycogenolytic treatment condition nor a specific nuclear-body biochemical function is inferred from the separate mouse-Agl transfection study. |
| GO:0005515 protein binding | IPI PMID:24837458 The carbohydrate-binding domain of overexpressed STBD1 is im... | REMOVE | Summary: The source reports association of GDE with STBD1, but the generic binding term lacks functional specificity. Reason: PMID:24837458 includes co-immunoprecipitation of tagged GDE with STBD1 and GST-STBD1 pull-down of endogenous GDE from mouse liver lysate. These are real association assays, not a purified two-component demonstration of direct human AGL binding. Remove the uninformative protein-binding annotation under the review policy without denying the association or inventing a new AGL molecular function. Supporting Evidence: PMID:24837458 could all bind to endogenous GDE, Laforin and GS |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798748 | UNDECIDED | Summary: Reactome models extracellular AGL after secretory-granule exocytosis, but direct release evidence remains unresolved. Reason: Event R-HSA-6798748 explicitly places human AGL in extracellular output set R-HSA-6806526. The underlying human-neutrophil fractionation study PMID:23650620 identifies compartment-associated proteins and calls for mobilization or surface-expression follow-up; its main text was read, but the AGL-level supplement and direct release measurements were not recovered. The immutable UniProt record describes cytoplasmic AGL and contains no signal-peptide or transmembrane feature, so it provides no conventional secretory route. These features do not exclude unconventional export. The event-specific extracellular assertion remains UNDECIDED rather than being treated as proven release or contamination. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6800434 | UNDECIDED | Summary: Reactome models extracellular AGL after ficolin-rich-granule exocytosis, but direct release evidence remains unresolved. Reason: Event R-HSA-6800434 explicitly places human AGL in extracellular output set R-HSA-6806481. The underlying human-neutrophil fractionation study PMID:23650620 identifies compartment-associated proteins and calls for mobilization or surface-expression follow-up; its main text was read, but the AGL-level supplement and direct release measurements were not recovered. The immutable UniProt record describes cytoplasmic AGL and contains no signal-peptide or transmembrane feature, so it provides no conventional secretory route. These features do not exclude unconventional export. The event-specific extracellular assertion remains UNDECIDED rather than being treated as proven release or contamination. |
| GO:0034774 secretory granule lumen | TAS Reactome:R-HSA-6798748 | UNDECIDED | Summary: Reactome assigns AGL to the secretory-granule lumen, while its intragranular topology remains unresolved. Reason: Human AGL is explicit in secretory-granule input set R-HSA-6800970 of event R-HSA-6798748. The human-neutrophil fractionation/proteomics experiment PMID:23650620 provides evidence of association with a compartment-defined fraction, but the recovered main text does not resolve AGL inside the lumen versus on the cytosolic surface or in a co-fractionating pool. Its AGL-level supplement was unavailable. A luminal assignment requires membrane crossing; the cytoplasmic UniProt localization and absence of signal-peptide/transmembrane features supply no established conventional route, but do not rule out other entry mechanisms. The exact lumen assignment therefore remains UNDECIDED. |
| GO:1904813 ficolin-1-rich granule lumen | TAS Reactome:R-HSA-6800434 | UNDECIDED | Summary: Reactome assigns AGL to the ficolin-rich-granule lumen, while its intragranular topology remains unresolved. Reason: Human AGL is explicit in ficolin-rich-granule input set R-HSA-6800431 of event R-HSA-6800434. The human-neutrophil fractionation/proteomics experiment PMID:23650620 provides evidence of association with a compartment-defined fraction, but the recovered main text does not resolve AGL inside the lumen versus on the cytosolic surface or in a co-fractionating pool. Its AGL-level supplement was unavailable. A luminal assignment requires membrane crossing; the cytoplasmic UniProt localization and absence of signal-peptide/transmembrane features supply no established conventional route, but do not rule out other entry mechanisms. The exact lumen assignment therefore remains UNDECIDED. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-71552 | ACCEPT | Summary: The AGL glucan-transfer reaction occurs in the cytosol. Reason: The live Reactome event identifies AGL [cytosol] as the catalyst that transfers a three-glucose segment from limit-dextrin branches. Retain the catalytic-compartment annotation; its source is more specific than generic cytoplasm. Supporting Evidence: file:human/AGL/AGL-uniprot.txt Transfers a segment of a (1->4)-alpha-D-glucan to a new...position in an acceptor, which may be glucose or a (1->4)-alpha-D-...glucan. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-71593 | ACCEPT | Summary: The AGL branch-hydrolysis reaction occurs in the cytosol. Reason: The live Reactome event identifies AGL [cytosol] as the glucosidase catalyst and releases free glucose from the exposed branch linkage. This is the established compartment for cytosolic glycogen debranching. Supporting Evidence: file:human/AGL/AGL-uniprot.txt Hydrolysis of (1->6)-alpha-D-glucosidic branch linkages in...glycogen phosphorylase limit dextrin. |
| GO:0005515 protein binding | IPI PMID:17908927 A role for AGL ubiquitination in the glycogen storage disord... | REMOVE | Summary: Malin associates with and ubiquitinates Agl, but protein binding does not describe a useful AGL activity. Reason: The full mouse-Agl transfection study PMID:17908927 reports malin association and ubiquitination of Agl. This supports regulation of the enzyme by a partner; it does not establish a more informative partner-directed molecular function executed by AGL. Remove the generic term without calling the interaction false or recasting the mouse construct as human protein. Supporting Evidence: PMID:17908927 Malin interacts with and promotes the ubiquitination of AGL |
| GO:0005737 cytoplasm | IDA PMID:17908927 A role for AGL ubiquitination in the glycogen storage disord... | ACCEPT | Summary: AGL has well-supported cytoplasmic localization. Reason: PMID:17908927 visualized tagged mouse Agl in mammalian host cells; its Methods identify the construct as mouse-liver cDNA. The broad human cytoplasmic location is independently supported by HPA cytosol staining and both human Reactome catalytic events. Retain the biologically secure localization while recording the construct boundary rather than rewriting the seeded evidence code. Supporting Evidence: PMID:17908927 AGL is cytoplasmic whereas Malin is predominately nuclear |
| GO:0043033 isoamylase complex | TAS PMID:1374391 Molecular cloning and nucleotide sequence of cDNA encoding h... | MARK AS OVER ANNOTATED | Summary: Isoamylase complex specifies a different catalytic system from mammalian glycogen debranching enzyme. Reason: GO:0043033 has a capable_of relation to GO:0019156 isoamylase activity (EC 3.2.1.68). That enzyme hydrolyses branches in glycogen, amylopectin and beta-limit dextrins and releases maltose or larger branches. Human AGL instead couples glucan transfer with EC 3.2.1.33 hydrolysis of the single branch-point glucose in phosphorylase limit dextrin. The shared debranching-enzyme name does not establish this specific catalytic-complex membership. This chemistry and ontology mismatch supports overannotation independently of the unrecovered full body of PMID:1374391. Human AGL monomers and dimers in PMID:40593796 are compatible with self-association, but do not identify an isoamylase complex; no monomer-only or plant-only exclusion is used. Supporting Evidence: file:human/AGL/AGL-uniprot.txt Hydrolysis of (1->6)-alpha-D-glucosidic branch linkages in...glycogen phosphorylase limit dextrin. PMID:40593796 existing in both monomeric and dimeric forms |
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Download this section (compressed HTML)Q: What physiological conditions control human AGL monomer-dimer exchange, and how does oligomerization affect the two catalytic steps?
Q: Does endogenous human AGL execute a distinct nuclear function, and what evidence resolves its specific granule-lumen and extracellular assignments?
Q: Does AGL directly participate in glycogen formation or branching correction during synthesis, beyond its established work in glycogen breakdown?
Experiment: Measure both catalytic activities in purified human monomeric and dimeric fractions under matched substrate conditions, and test whether the assembly distribution persists in native cells.
Experiment: Use endogenous AGL detection and controlled fractionation to distinguish nuclear, SR-associated and granule-luminal pools, with topology and release assays for the neutrophil assignments.
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