ALDOA encodes fructose-bisphosphate aldolase A, the muscle/red-cell isozyme of the ubiquitous class-I fructose-bisphosphate aldolase (three vertebrate isozymes exist: A in muscle, B in liver, C in brain). It is a cytosolic homotetramer that uses a Schiff-base (active-site lysine) mechanism to catalyze the reversible aldol cleavage of beta-D-fructose 1,6-bisphosphate into dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (EC 4.1.2.13), the fourth step of glycolysis, and the reverse aldol condensation in gluconeogenesis. Aldolase A is highly abundant in skeletal muscle and erythrocytes. Beyond catalysis it is a well-documented moonlighting protein that binds F-actin and other cytoskeletal components (and the actin nucleation-promoting factor WASP) via its active-site region, links glycolysis to cytoskeletal dynamics, and binds RNA. Loss-of-function variants cause glycogen storage disease type XII (aldolase A deficiency), presenting as hereditary nonspherocytic hemolytic anemia frequently accompanied by myopathy, exercise intolerance and rhabdomyolysis (often triggered by febrile illness).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004332 fructose-bisphosphate aldolase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (PAN-GO) inference of the core catalytic molecular function of aldolase A, transferred across the class-I fructose-bisphosphate aldolase family (PANTHER PTHR11627). This is correct and central: aldolase A cleaves fructose-1,6-bisphosphate to DHAP and glyceraldehyde-3-phosphate (EC 4.1.2.13). Reason: Correct core molecular function, well supported by direct enzymatic and structural studies of the human muscle enzyme and consistent across the family. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Reaction=beta-D-fructose 1,6-bisphosphate = D-glyceraldehyde 3- PMID:14766013 We have identified a new mutation in the FBP (fructose 1,6-bisphosphate) |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that aldolase A acts in the cytosol. Glycolysis/gluconeogenesis occur in the cytosol and aldolase A is a soluble cytoplasmic enzyme. Reason: Correct primary subcellular location for the catalytic activity; consistent with the cytoplasmic classification in UniProt and with Reactome cytosol annotations. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt glycolysis and gluconeogenesis (PubMed:14766013). In addition, also |
| GO:0006096 glycolytic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that aldolase A participates in glycolysis. This is the canonical biological process for aldolase A (the fourth glycolytic step). Reason: Correct core biological process, supported by direct study of the human enzyme and the deficiency phenotype. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt glycolysis and gluconeogenesis (PubMed:14766013). In addition, also |
| GO:0030388 fructose 1,6-bisphosphate metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference; fructose-1,6-bisphosphate is the direct substrate of aldolase A, so this metabolic process term is appropriate at the substrate level. Reason: Accurately captures the substrate-level metabolic process (F1,6BP is consumed in glycolysis and produced in gluconeogenesis by this enzyme). Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Reaction=beta-D-fructose 1,6-bisphosphate = D-glyceraldehyde 3- |
| GO:0004332 fructose-bisphosphate aldolase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment of the core catalytic activity from InterPro FBA_I signature, RHEA:14729 and EC 4.1.2.13. Redundant with experimental/IBA annotations of the same function. Reason: Correct core molecular function; the EC/RHEA/InterPro mapping matches the experimentally established reaction. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt ChEBI:CHEBI:32966, ChEBI:CHEBI:57642, ChEBI:CHEBI:59776; EC=4.1.2.13; |
| GO:0006000 fructose metabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA electronic inference of involvement in fructose metabolism. Aldolase A acts on fructose-1,6-bisphosphate (a fructose derivative); this is broader/context term rather than the core glycolytic role. Reason: Not incorrect, but general relative to the specific F1,6BP/glycolytic role; kept as non-core context. (Unlike the liver isozyme ALDOB, aldolase A is not the principal dietary fructolysis enzyme.) Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Reaction=beta-D-fructose 1,6-bisphosphate = D-glyceraldehyde 3- |
| GO:0006096 glycolytic process | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment (InterPro/UniPathway) of the glycolytic process, redundant with the experimental and IBA glycolysis annotations. Reason: Correct core biological process, consistent with the UniPathway glycolysis step 4/4 mapping. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt glycolysis and gluconeogenesis (PubMed:14766013). In addition, also |
| GO:0030388 fructose 1,6-bisphosphate metabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA electronic assignment of the F1,6BP metabolic process, redundant with the IBA and IDA annotations of the same term. Reason: Correct substrate-level metabolic process for aldolase A. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Reaction=beta-D-fructose 1,6-bisphosphate = D-glyceraldehyde 3- |
| GO:0031430 M band | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: SubCell keyword mapping placing aldolase A at the sarcomeric M band. UniProt records that in skeletal muscle aldolase A accumulates around the M line and within the I band (colocalizing with FBP2), by similarity to the rabbit enzyme. This reflects a muscle-specific structural association rather than the enzyme's core catalytic role. Reason: Supported as a muscle-specific localization/moonlighting association with the contractile apparatus, but not the core (cytosolic) site of glycolytic function. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Cytoplasm, myofibril, sarcomere, M line |
| GO:0031674 I band | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: SubCell keyword mapping placing aldolase A at the sarcomeric I band, matching the described accumulation within the I band on both sides of the Z line in skeletal muscle. Reason: Muscle-specific structural localization (moonlighting with the sarcomere), not the core cytosolic catalytic site. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Cytoplasm, myofibril, sarcomere, I band |
| GO:0070061 fructose binding | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA electronic inference of fructose(-phosphate) binding, matching the direct binding of the fructose-1,6-bisphosphate substrate demonstrated crystallographically and biochemically. Reason: Correct substrate-binding molecular function directly supported by the crystal structure of human muscle aldolase complexed with fructose 1,6-bisphosphate. Supporting Evidence: PMID:10048322 Crystals were also soaked with the natural substrate (fructose 1,6-bisphosphate) |
| GO:0005515 protein binding | IPI PMID:20849852 Proliferating cell nuclear antigen in the cytoplasm interact... | MARK AS OVER ANNOTATED | Summary: IntAct-curated binary interaction (with PCNA, P12004) from a study reporting that cytoplasmic PCNA associates with several glycolytic enzymes. The bare "protein binding" term is uninformative about aldolase A function. Reason: Per curation policy, bare protein binding IPIs are marked as over-annotated rather than removed; the interaction itself is real but does not convey a specific molecular function. Supporting Evidence: PMID:20849852 PCNA is also associated with six glycolytic enzymes |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | MARK AS OVER ANNOTATED | Summary: IntAct binary interaction (with ALDOB, P05062) from a large-scale human liver protein-interaction network study. Bare protein-binding term, uninformative. Reason: Bare protein binding IPI; interaction is real (isozyme co-purification) but conveys no specific function. Supporting Evidence: PMID:21988832 protein interaction network of the human liver |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MARK AS OVER ANNOTATED | Summary: IntAct binary interaction (with ALDOC, P09972) from a quantitative human interactome study. Bare protein-binding term. Reason: Bare protein binding IPI; not informative about aldolase A's molecular function. Supporting Evidence: PMID:26496610 human interactome in three quantitative dimensions |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: IntAct binary interaction (with ALDOC, P09972) from a large-scale interactome map. Bare protein-binding term. Reason: Bare protein binding IPI; uninformative for molecular function. Supporting Evidence: PMID:28514442 Architecture of the human interactome |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MARK AS OVER ANNOTATED | Summary: IntAct binary interaction (with ALDOC, P09972) from a study of interaction disruption by genetic variants. Bare protein-binding term. Reason: Bare protein binding IPI; uninformative for molecular function. Supporting Evidence: PMID:31515488 disruption of protein interactions by genetic variants |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: IntAct binary interactions (with ALDOB/ALDOC/CARM1) from dual proteome-scale interactome networks. Bare protein-binding term. Reason: Bare protein binding IPI; interactions are real but the term conveys no specific function. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling |
| GO:0042802 identical protein binding | IPI PMID:10944123 Initial enzyme for glycosylphosphatidylinositol biosynthesis... | KEEP AS NON CORE | Summary: IntAct self-interaction annotation (ALDOA-ALDOA). Aldolase A is a physiological homotetramer, so self-association is real, but this generic binding term is not the core molecular function. Reason: Homo-oligomerization is genuine (homotetramer) and more informative than bare protein binding, but it is a structural/assembly property rather than the catalytic core function. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Homotetramer (By similarity). Interacts with SNX9 and WAS (By |
| GO:0042802 identical protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | KEEP AS NON CORE | Summary: IntAct self-interaction annotation (ALDOA-ALDOA) from the human liver interactome study, consistent with the homotetrameric assembly. Reason: Reflects the real homotetramer, but is a structural property rather than the core catalytic function. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Homotetramer (By similarity). Interacts with SNX9 and WAS (By |
| GO:0006094 gluconeogenesis | TAS Reactome:R-HSA-70263 | ACCEPT | Summary: Reactome traceable assertion that aldolase A participates in gluconeogenesis, where it catalyzes the reverse aldol condensation of DHAP + G3P into fructose-1,6-bisphosphate. Reason: Correct core process; the aldolase reaction is reversible and functions in both glycolysis and gluconeogenesis. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt glycolysis and gluconeogenesis (PubMed:14766013). In addition, also |
| GO:0061621 canonical glycolysis | TAS Reactome:R-HSA-70171 | ACCEPT | Summary: Reactome traceable assertion for the canonical (glucose-derived) glycolytic pathway, the specific glycolysis subtype for aldolase A. Reason: Correct and appropriately specific core process term. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt bisphosphate (FBP) into two triose phosphate and plays a key role in |
| GO:0004332 fructose-bisphosphate aldolase activity | EXP PMID:6696436 Human skeletal-muscle aldolase: N-terminal sequence analysis... | ACCEPT | Summary: Experimental annotation of the core catalytic activity, tied to characterization of human skeletal-muscle aldolase (purified from human muscle, sequenced). Supports the identity and catalytic function of the muscle isozyme. Reason: Core molecular function, experimentally grounded in the purified human muscle enzyme. Supporting Evidence: PMID:6696436 Fructose-1,6-bisphosphate aldolase was purified from human skeletal-muscle |
| GO:0061621 canonical glycolysis | IDA PMID:14766013 Human aldolase A natural mutants: relationship between flexi... | ACCEPT | Summary: Direct-assay annotation of the canonical glycolysis role, from functional characterization of wild-type and GSD12 mutant human aldolase A enzymes. Reason: Core process; functional/kinetic characterization of the human enzyme supports its glycolytic role. Supporting Evidence: PMID:14766013 We have identified a new mutation in the FBP (fructose 1,6-bisphosphate) |
| GO:0006096 glycolytic process | IDA PMID:14766013 Human aldolase A natural mutants: relationship between flexi... | ACCEPT | Summary: Direct-assay annotation of the glycolytic process, from kinetic characterization of human aldolase A and its disease mutants. Reason: Core biological process, directly supported by enzymatic characterization. Supporting Evidence: PMID:14766013 We have identified a new mutation in the FBP (fructose 1,6-bisphosphate) |
| GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus | IDA PMID:40446798 A microbial amino-acid-conjugated bile acid, tryptophan-chol... | KEEP AS NON CORE | Summary: IDA from a 2025 study showing that a microbial bile acid (Trp-CA) acting through the orphan GPCR MRGPRE signals via an MRGPRE-beta-arrestin-1-ALDOA pathway to improve glucose homeostasis, implicating aldolase A downstream of a glucose-regulatory signaling axis. Reason: A genuine but specialized, context-specific signaling role (beta-arrestin-1-ALDOA branch of MRGPRE signaling); not the core glycolytic function. Kept as non-core per the experimental IDA (curator read the full text). Supporting Evidence: PMID:40446798 MRGPRE-Ξ²-arrestin-1-aldolase A (ALDOA) signaling pathways contribute to the metabolic benefits |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | MARK AS OVER ANNOTATED | Summary: High-throughput proximity-biotinylation (BioID) proteomics detected aldolase A among hundreds of proteins near the E-cadherin cytoplasmic tail. This is a proximity hit, not a demonstrated direct/functional cadherin interaction. Reason: Bystander detection in a large proximity-proteomics dataset; not a specific functional binding activity of aldolase A. Retained (not removed) as it derives from a real experimental dataset. Supporting Evidence: PMID:25468996 identify 561 proteins in the vicinity of the cytoplasmic tail of E-cadherin |
| GO:0005515 protein binding | IPI PMID:23355646 Identification of sperm head proteins involved in zona pellu... | MARK AS OVER ANNOTATED | Summary: IPI (with partner Q12836) from the sperm-head zona-pellucida proteomics study. Bare protein-binding term. Reason: Bare protein binding IPI; uninformative about molecular function. Supporting Evidence: PMID:23355646 sperm proteins are multifaceted or moonlighting proteins |
| GO:0007339 binding of sperm to zona pellucida | IMP PMID:23355646 Identification of sperm head proteins involved in zona pellu... | KEEP AS NON CORE | Summary: IMP from a study identifying sperm-head glycolytic enzymes (including aldolase A) recognized by antisperm antibodies and reactive with recombinant zona-pellucida proteins, and validated in functional zona-binding tests. The authors explicitly frame these as moonlighting roles. Reason: A plausible moonlighting reproductive role reported experimentally; not the core metabolic function. Retained as non-core (defer to the curator's IMP; full text not in cache). Supporting Evidence: PMID:23355646 functional zona binding tests |
| GO:0061827 sperm head | IDA PMID:23355646 Identification of sperm head proteins involved in zona pellu... | KEEP AS NON CORE | Summary: IDA localizing aldolase A (among other glycolytic enzymes) to the sperm head, though the same proteins also function in the flagellum. Reason: Specialized cell-type localization consistent with a moonlighting sperm role; not the core cytosolic site. Supporting Evidence: PMID:23355646 Several of the proteins were localized on the sperm head |
| GO:0034774 secretory granule lumen | TAS Reactome:R-HSA-6798748 | KEEP AS NON CORE | Summary: Reactome localization to secretory granule lumen via the neutrophil-degranulation exocytosis pathway, where abundant cytosolic proteins such as aldolase A are cargo of granule/secretion events. Reason: Reflects granule/secretion proteomics rather than the core cytosolic function; kept as non-core. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Reactome; R-HSA-6798695; Neutrophil degranulation. |
| GO:1904724 tertiary granule lumen | TAS Reactome:R-HSA-6798745 | KEEP AS NON CORE | Summary: Reactome localization to tertiary granule lumen via the neutrophil-degranulation pathway; aldolase A appears as granule cargo. Reason: Secretion/granule-proteomics localization, non-core relative to cytosolic glycolysis. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Reactome; R-HSA-6798695; Neutrophil degranulation. |
| GO:1904813 ficolin-1-rich granule lumen | TAS Reactome:R-HSA-6800434 | KEEP AS NON CORE | Summary: Reactome localization to ficolin-1-rich granule lumen via neutrophil degranulation; aldolase A is granule cargo. Reason: Secretion/granule-proteomics localization, non-core. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Reactome; R-HSA-6798695; Neutrophil degranulation. |
| GO:0070062 extracellular exosome | HDA PMID:12519789 Proteomic and biochemical analyses of human B cell-derived e... | KEEP AS NON CORE | Summary: High-throughput proteomic detection of aldolase A in B cell-derived exosomes. As an abundant cytosolic protein, aldolase A is a frequent bystander in exosome proteomes. Reason: Bystander localization in exosome proteomics; not the core cytosolic site of function. Supporting Evidence: PMID:12519789 human B cell-derived exosomes |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: Proteomic detection of aldolase A in prostatic-secretion (urinary) exosomes; a bystander localization. Reason: Exosome-proteomics bystander detection; non-core. Supporting Evidence: PMID:23533145 exosomes isolated from expressed prostatic |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: Aldolase A detected in an NK-cell membrane-proteome dataset. This likely reflects co-purification of the abundant cytosolic enzyme; not a bona fide integral-membrane localization. Reason: Over-broad/likely-contaminant localization from a membrane-proteome dataset; aldolase A has no membrane-spanning features. Retained (not removed) as it derives from a real dataset. Supporting Evidence: PMID:19946888 membrane proteome of NK cells |
| GO:0005634 nucleus | HDA PMID:21630459 Proteomic characterization of the human sperm nucleus. | KEEP AS NON CORE | Summary: Aldolase A detected in a human sperm-nucleus proteome. A bystander/partitioning detection rather than an established nuclear function. Reason: Proteomic nuclear detection without a demonstrated nuclear function; kept as non-core. Supporting Evidence: PMID:21630459 human sperm nucleus |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | KEEP AS NON CORE | Summary: mRNA-interactome capture (UV-crosslinking + oligo(dT)) identified aldolase A among the mRNA-bound proteome. Several glycolytic enzymes are known RNA-binding moonlighters, so this is a plausible non-catalytic activity. Reason: Real moonlighting RNA-binding activity detected by interactome capture, but not the core catalytic function; kept as non-core. Supporting Evidence: PMID:22681889 identify the mRNA-bound proteome |
| GO:0005576 extracellular region | HDA PMID:23580065 Shotgun proteomics reveals specific modulated protein patter... | KEEP AS NON CORE | Summary: Aldolase A detected in tear-fluid shotgun proteomics; a bystander extracellular detection of an abundant cytosolic enzyme. Reason: Extracellular-fluid proteomics detection; non-core relative to cytosolic function. Supporting Evidence: PMID:23580065 in tears of |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: Aldolase A detected in parotid-gland exosome proteomics; bystander localization. Reason: Exosome-proteomics bystander detection; non-core. Supporting Evidence: PMID:19199708 human parotid gland exosomes |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Aldolase A detected in urinary-exosome proteomics; bystander localization. Reason: Exosome-proteomics bystander detection; non-core. Supporting Evidence: PMID:19056867 proteomics and phosphoproteomics of urinary exosomes |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: Aldolase A detected in B-cell exosome proteomics; bystander localization. Reason: Exosome-proteomics bystander detection; non-core. Supporting Evidence: PMID:20458337 MHC class II-associated proteins in B-cell exosomes |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-481007 | KEEP AS NON CORE | Summary: Reactome localization to extracellular region via platelet alpha-granule exocytosis; abundant cytosolic aldolase A appears as granule/secretion cargo. Reason: Secretion-pathway localization, non-core relative to cytosolic function. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Reactome; R-HSA-114608; Platelet degranulation. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798745 | KEEP AS NON CORE | Summary: Reactome extracellular-region localization via neutrophil-degranulation exocytosis. Reason: Secretion-pathway localization, non-core. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Reactome; R-HSA-6798695; Neutrophil degranulation. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798748 | KEEP AS NON CORE | Summary: Reactome extracellular-region localization via neutrophil-degranulation exocytosis. Reason: Secretion-pathway localization, non-core. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Reactome; R-HSA-6798695; Neutrophil degranulation. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6800434 | KEEP AS NON CORE | Summary: Reactome extracellular-region localization via neutrophil-degranulation exocytosis. Reason: Secretion-pathway localization, non-core. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Reactome; R-HSA-6798695; Neutrophil degranulation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-71495 | ACCEPT | Summary: Reactome cytosol localization for the aldolase reaction (DHAP + G3P -> F1,6BP, gluconeogenic direction). Correct core localization. Reason: Correct primary cytosolic localization for aldolase A catalysis. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt glycolysis and gluconeogenesis (PubMed:14766013). In addition, also |
| GO:0005829 cytosol | TAS Reactome:R-HSA-71496 | ACCEPT | Summary: Reactome cytosol localization for the aldolase reaction (F1,6BP cleavage, glycolytic direction). Correct core localization. Reason: Correct primary cytosolic localization for aldolase A catalysis. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt glycolysis and gluconeogenesis (PubMed:14766013). In addition, also |
| GO:0031093 platelet alpha granule lumen | TAS Reactome:R-HSA-481007 | KEEP AS NON CORE | Summary: Reactome localization to platelet alpha-granule lumen via the platelet-degranulation pathway; aldolase A appears as granule cargo. Reason: Secretion/granule-proteomics localization, non-core. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Reactome; R-HSA-114608; Platelet degranulation. |
| GO:0051289 protein homotetramerization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS transfer (from rabbit ALDOA, P00883) that aldolase A forms a homotetramer, the functional quaternary state established structurally and biochemically. Reason: Genuine (aldolase A is a homotetramer) but a structural/assembly property rather than the core catalytic function. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Homotetramer (By similarity). Interacts with SNX9 and WAS (By |
| GO:0004332 fructose-bisphosphate aldolase activity | IDA PMID:9244396 Mode of interactions of human aldolase isozymes with cytoske... | ACCEPT | Summary: IDA of the core catalytic activity in a study of human aldolase isozyme interactions with the cytoskeleton (aldolase A activity assayed alongside its actin binding). Reason: Core molecular function, directly assayed for the human enzyme. Supporting Evidence: PMID:9244396 Three isoforms of fructose-1,6-bisphosphate aldolase |
| GO:0008092 cytoskeletal protein binding | IDA PMID:9244396 Mode of interactions of human aldolase isozymes with cytoske... | KEEP AS NON CORE | Summary: IDA that aldolase A binds cytoskeletal (actin-containing) filaments; aldolase A binds the skeletal-muscle cytoskeleton most tightly among the isozymes, and binding is inhibited by substrate (F1,6BP/F1P). Reason: Well-documented moonlighting cytoskeletal binding activity, but not the core catalytic function. Supporting Evidence: PMID:9244396 bound more tightly to the skeletal muscle cytoskeleton among the three isozymes |
| GO:0008360 regulation of cell shape | IDA PMID:9244396 Mode of interactions of human aldolase isozymes with cytoske... | KEEP AS NON CORE | Summary: IDA that aldolase A, via its actin/cytoskeleton association, reversibly inhibited the contraction of permeabilized MRC-5 fibroblasts, suggesting a role in regulating cell contraction/shape. Reason: A moonlighting cytoskeletal/cell-shape role tied to actin binding, not the core metabolic function. Supporting Evidence: PMID:9244396 reversibly inhibited the contraction of MRC-5 cells |
| GO:0015629 actin cytoskeleton | IDA PMID:9244396 Mode of interactions of human aldolase isozymes with cytoske... | KEEP AS NON CORE | Summary: IDA localizing aldolase A to the actin cytoskeleton: it bound actin filaments in the stress fibers of permeabilized fibroblasts. Reason: Moonlighting cytoskeletal localization tied to actin binding; not the core cytosolic catalytic site. Supporting Evidence: PMID:9244396 A bound to the actin filaments in the stress fibers within the cell. Aldolase A |
| GO:0030388 fructose 1,6-bisphosphate metabolic process | IDA PMID:9244396 Mode of interactions of human aldolase isozymes with cytoske... | ACCEPT | Summary: IDA of the F1,6BP metabolic process, consistent with the catalytic activity assayed in this study. Reason: Correct substrate-level metabolic process for aldolase A. Supporting Evidence: PMID:9244396 Three isoforms of fructose-1,6-bisphosphate aldolase |
| GO:0070061 fructose binding | IDA PMID:10048322 Crystal structure of human muscle aldolase complexed with fr... | ACCEPT | Summary: IDA of fructose(-1,6-bisphosphate) binding, directly supported by the crystal structure of human muscle aldolase soaked with the natural substrate. Reason: Correct substrate-binding molecular function, structurally demonstrated. Supporting Evidence: PMID:10048322 Crystals were also soaked with the natural substrate (fructose 1,6-bisphosphate) |
| GO:0070061 fructose binding | IDA PMID:14766013 Human aldolase A natural mutants: relationship between flexi... | ACCEPT | Summary: IDA of substrate (fructose 1,6-bisphosphate) binding from kinetic characterization (KM for FBP) of human aldolase A and its mutants. Reason: Correct substrate-binding function, supported by measured KM values for F1,6BP. Supporting Evidence: PMID:14766013 We have identified a new mutation in the FBP (fructose 1,6-bisphosphate) |
| GO:0070062 extracellular exosome | IDA PMID:17641064 Exosomes with immune modulatory features are present in huma... | KEEP AS NON CORE | Summary: Aldolase A detected in human breast-milk exosomes; a bystander localization of an abundant cytosolic protein. Reason: Exosome-proteomics bystander detection; non-core. Supporting Evidence: PMID:17641064 Exosomes with immune modulatory features are present in human breast milk |
| GO:0003779 actin binding | TAS PMID:1008835 Aldolase binding to actin-containing filaments. Formation of... | KEEP AS NON CORE | Summary: TAS that aldolase binds actin-containing filaments (F-actin / F-actin-tropomyosin), forming ordered paracrystalline bundles. A classic demonstration of the moonlighting actin-binding activity. Reason: Genuine moonlighting actin-binding activity, distinct from the core catalytic function. Supporting Evidence: PMID:1008835 when aldolase binds to F-actin or F-actin-tropomyosin, highly ordered paracrystalline structures are formed |
| GO:0006000 fructose metabolic process | IMP PMID:14615364 Hemolytic anemia and severe rhabdomyolysis caused by compoun... | KEEP AS NON CORE | Summary: IMP from a GSD12 (aldolase A deficiency) case with compound heterozygous ALDOA mutations (Arg303X/Cys338Tyr) causing hemolytic anemia and rhabdomyolysis, linking loss of aldolase A to disrupted fructose/carbohydrate metabolism. Reason: Correct in that aldolase A acts on a fructose-derived substrate, but general relative to the specific glycolytic role; kept as non-core context. Supporting Evidence: PMID:14615364 converts fructose-1,6-bisphosphate to dihydroxyacetone phosphate and |
| GO:0006096 glycolytic process | IMP PMID:14615364 Hemolytic anemia and severe rhabdomyolysis caused by compoun... | ACCEPT | Summary: IMP linking loss-of-function ALDOA mutations to impaired glycolysis in a severely affected aldolase A deficiency patient. Reason: Core biological process; the deficiency phenotype supports the glycolytic role of aldolase A. Supporting Evidence: PMID:14615364 converts fructose-1,6-bisphosphate to dihydroxyacetone phosphate and |
| GO:0006754 ATP biosynthetic process | IMP PMID:14615364 Hemolytic anemia and severe rhabdomyolysis caused by compoun... | KEEP AS NON CORE | Summary: IMP attributing an ATP-biosynthesis role to aldolase A, inferred from the muscle energy failure (rhabdomyolysis) in aldolase A deficiency. This is a downstream consequence of glycolytic flux rather than a direct aldolase function. Reason: Indirect/downstream role (glycolytic ATP production) rather than a direct molecular activity; kept as non-core, deferring to the curator's full-text IMP. Supporting Evidence: PMID:14615364 splenectomy at age 3 and increasing muscle weakness, with death at age 4 |
| GO:0006941 striated muscle contraction | IMP PMID:14615364 Hemolytic anemia and severe rhabdomyolysis caused by compoun... | KEEP AS NON CORE | Summary: IMP from aldolase A deficiency with muscle weakness and rhabdomyolysis, linking aldolase A (energy supply / cytoskeletal association) to striated muscle function. Reason: A physiologically relevant but indirect muscle role (via energy metabolism and sarcomeric association), not the core molecular function; non-core. Supporting Evidence: PMID:14615364 splenectomy at age 3 and increasing muscle weakness, with death at age 4 |
| GO:0007015 actin filament organization | TAS PMID:1008835 Aldolase binding to actin-containing filaments. Formation of... | KEEP AS NON CORE | Summary: TAS that aldolase organizes actin filaments into ordered paracrystalline bundles, an in-vitro demonstration of its actin-crosslinking/organizing moonlighting activity. Reason: Moonlighting actin-organizing role (bundle/paracrystal formation), not the core catalytic function. Supporting Evidence: PMID:1008835 tightly packed filament bundles cross-banded at 36 nm intervals |
| GO:0015631 tubulin binding | TAS PMID:17329259 A hydrophobic pocket in the active site of glycolytic aldola... | MARK AS OVER ANNOTATED | Summary: This annotation cites PMID:17329259, which reports the structural basis of aldolase binding to the Wiskott-Aldrich syndrome protein (WASP) via a hydrophobic active-site pocket, competitive with substrate and with actin/cortactin. The paper concerns actin-related (WASP) binding, not tubulin; tubulin binding is not supported by this reference. Reason: The cited reference does not establish tubulin binding; it demonstrates WASP/actin- pathway binding at the aldolase active site. Marked as over-annotated rather than removed (aldolase is broadly promiscuous, and this is a TAS from the curator). Supporting Evidence: PMID:17329259 aldolase binds to highly acidic amino acid sequences, including the C terminus of the Wiskott-Aldrich syndrome protein |
| GO:0031674 I band | TAS PMID:1008835 Aldolase binding to actin-containing filaments. Formation of... | KEEP AS NON CORE | Summary: TAS placing aldolase at the sarcomeric I band, consistent with its documented actin/ thin-filament association and the muscle-specific accumulation within the I band. Reason: Muscle-specific structural localization (moonlighting with the sarcomere/thin filament), not the core cytosolic catalytic site. Supporting Evidence: file:human/ALDOA/ALDOA-uniprot.txt Cytoplasm, myofibril, sarcomere, I band |
| GO:0046716 muscle cell cellular homeostasis | IMP PMID:14615364 Hemolytic anemia and severe rhabdomyolysis caused by compoun... | KEEP AS NON CORE | Summary: IMP from aldolase A deficiency, where loss of aldolase A causes myopathy and rhabdomyolysis, indicating a role in maintaining muscle-cell homeostasis (energy supply / integrity). Reason: A physiologically relevant but indirect role (downstream of glycolytic energy metabolism); non-core. Supporting Evidence: PMID:14615364 splenectomy at age 3 and increasing muscle weakness, with death at age 4 |
| GO:0004332 fructose-bisphosphate aldolase activity | IDA PMID:14766013 Human aldolase A natural mutants: relationship between flexi... | ACCEPT | Summary: IDA of the core catalytic activity from kinetic characterization of recombinant human aldolase A wild-type and disease mutants (KM/kcat/Tm measurements). Reason: Core molecular function, directly measured for the human enzyme. Supporting Evidence: PMID:14766013 We have identified a new mutation in the FBP (fructose 1,6-bisphosphate) |
| GO:0030388 fructose 1,6-bisphosphate metabolic process | IDA PMID:14766013 Human aldolase A natural mutants: relationship between flexi... | ACCEPT | Summary: IDA of the F1,6BP metabolic process from functional characterization of human aldolase A and its mutants. Reason: Correct substrate-level metabolic process, directly supported. Supporting Evidence: PMID:14766013 We have identified a new mutation in the FBP (fructose 1,6-bisphosphate) |
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